Activation of a hypothalamus-habenula circuit by mechanical stimulation inhibits cocaine addiction-like behaviors.

BACKGROUND: Mechanoreceptor activation modulates GABA neuron firing and dopamine (DA) release in the mesolimbic DA system, an area implicated in reward and substance abuse. The lateral habenula (LHb), the lateral hypothalamus (LH), and the mesolimbic DA system are not only reciprocally connected, but also involved in drug reward. We explored the effects of mechanical stimulation (MS) on cocaine addiction-like behaviors and the role of the LH-LHb circuit in the MS effects. MS was performed over ulnar nerve and the effects were evaluated by using drug seeking behaviors, optogenetics, chemogenetics, electrophysiology and immunohistochemistry. RESULTS: Mechanical stimulation attenuated locomotor activity in a nerve-dependent manner and 50-kHz ultrasonic vocalizations (USVs) and DA release in nucleus accumbens (NAc) following cocaine injection. The MS effects were ablated by electrolytic lesion or optogenetic inhibition of LHb. Optogenetic activation of LHb suppressed cocaine-enhanced 50 kHz USVs and locomotion. MS reversed cocaine suppression of neuronal activity of LHb. MS also inhibited cocaine-primed reinstatement of drug-seeking behavior, which was blocked by chemogenetic inhibition of an LH-LHb circuit. CONCLUSION: These findings suggest that peripheral mechanical stimulation activates LH-LHb pathways to attenuate cocaine-induced psychomotor responses and seeking behaviors.

Activation of a hypothalamus-habenula circuit by mechanical stimulation inhibits cocaine addiction-like behaviors

BACKGROUND: Mechanoreceptor activation modulates GABA neuron firing and dopamine (DA) release in the mesolimbic DA system, an area implicated in reward and substance abuse. The lateral habenula (LHb), the lateral hypothalamus (LH), and the mesolimbic DA system are not only reciprocally connected, but also involved in drug reward. We explored the effects of mechanical stimulation (MS) on cocaine addiction-like behaviors and the role of the LH-LHb circuit in the MS effects. MS was performed over ulnar nerve and the effects were evaluated by using drug seeking behaviors, optogenetics, chemogenetics, electrophysiology and immunohistochemistry. RESULTS: Mechanical stimulation attenuated locomotor activity in a nerve-dependent manner and 50-kHz ultrasonic vocalizations (USVs) and DA release in nucleus accumbens (NAc) following cocaine injection. The MS effects were ablated by electrolytic lesion or optogenetic inhibition of LHb. Optogenetic activation of LHb suppressed cocaine-enhanced 50 kHz USVs and locomotion. MS reversed cocaine suppression of neuronal activity of LHb. MS also inhibited cocaine-primed reinstatement of drug-seeking behavior, which was blocked by chemogenetic inhibition of an LH-LHb circuit. CONCLUSION: These findings suggest that peripheral mechanical stimulation activates LH-LHb pathways to attenuate cocaine-induced psychomotor responses and seeking behaviors.

Suppressive activity of RGX-365 on HMGB1-mediated septic responses

Abstract RGX-365 is the main fraction of black ginseng conmprising protopanaxatriol (PPT)-type rare ginsenosides (ginsenosides Rg4, Rg6, Rh4, Rh1, and Rg2). No studies on the antiseptic activity of RGX-365 have been reported. High mobility group box 1 (HMGB1) is recognized as a late mediator of sepsis, and the inhibition of HMGB1 release and recovery of vascular barrier integrity have emerged as attractive therapeutic strategies for the management of sepsis. In this study, we examined the effects of RGX-365 on HMGB1-mediated septic responses and survival rate in a mouse sepsis model. RGX-365 was administered to the mice after HMGB1 challenge. The antiseptic activity of RGX-365 was assessed based on the production of HMGB1, measurement of permeability, and septic mouse mortality using a cecal ligation and puncture (CLP)-induced sepsis mouse model and HMGB1-activated human umbilical vein endothelial cells (HUVECs). We found that RGX-365 significantly reduced HMGB1 release from LPS- activated HUVECs and CLP-induced release of HMGB1 in mice. RGX-365 also restored HMGB1-mediated vascular disruption and inhibited hyperpermeability in the mice. In addition, treatment with RGX-365 reduced sepsis-related mortality in vivo. Our results suggest that RGX- 365 reduces HMGB1 release and septic mortality in vivo, indicating that it is useful in the treatment of sepsis.

COMPARING OUTCOMES OF THE ANKLE ARTHRODESIS BY USING TWO DIFFERENT MATERIALS VIA A TRANSFIBULAR APPROACH.

OBJECTIVE: To compare clinical and radiologic results and complications of patients who underwent arthrodesis using a transfibular approach with either a cannulated screw or an anterior fusion plate. METHODS: Patients who underwent ankle arthrodesis were divided into two groups according to the used materials: 6.5 mm cannulated screw (A) and anterior fusion plate (B). The clinical scores were compared between groups. The radiologic results were then assessed by union time. The results were statistically analyzed using SPSS 20. RESULTS: There was no significant difference between both groups in the American Orthopedic Foot & Ankle Society (AOFAS) score (p = 0.75), and in the visual analog scale (p = 0.42). In group B, two cases included wound infection at the surgical site. In tt A, the mean union time was 10.5 ± 2.3 weeks. In group B, it was 7.8 ± 1.3. There was a statistically significant difference (p = 0.007) between union time in both groups. CONCLUSION: Anterior fusion plate is an effective method for shorter union time, but the surgeon should be careful with the surgical wound at the skin incision site in the lesion of the distal tibia. Level of Evidence III, Retrospective comparative study.

OBJETIVO: Comparar os resultados clínicos e radiológicos assim como as complicações de pacientes sujeitos a artrodese de abordagem transfibular com o uso de parafuso canulado ou placa óssea anterior. MÉTODOS: Pacientes sujeitos a artrodese do tornozelo foram divididos em dois grupos de acordo com os materiais usados: parafuso canulado de 6,5 mm (A) e placa óssea anterior (B). Os escores clínicos de ambos os grupos foram comparados e os resultados radiológicos foram avaliados de acordo com o tempo de união óssea. Os resultados foram analisados estatisticamente usando SPSS 20. RESULTADOS: Não houve diferença significativa entre os grupos quanto ao escore American Orthopedic Foot & Ankle Society (AOFAS) (p = 0,75) e a escala visual analógica (p = 0,42). No grupo B, ocorreu infecção na área da cirurgia em dois casos. No grupo A, a média de tempo de união foi de 10,5 ± 2,3 semanas. No grupo B, este foi de 7,8 ± 1,3. Constatou-se diferença estatisticamente significante (p = 0,007) quanto ao tempo de união em ambos os grupos. CONCLUSÃO: Os autores concluíram que a placa óssea anterior é um método eficiente para tempos de união curtos, porém o cirurgião deve ficar atento à ferida cirúrgica na área de incisão da pele em casos de lesão na tíbia distal. Nível de Evidência III, Estudo retrospectivo comparativo.

Comparing outcomes of the ankle arthrodesis by using two different materials via a transfibular approach / Comparação dos resultados da artrodese do tornozelo usando dois diferentes materiais através de uma abordagem transfibular

ABSTRACT Objective: To compare clinical and radiologic results and complications of patients who underwent arthrodesis using a transfibular approach with either a cannulated screw or an anterior fusion plate. Methods: Patients who underwent ankle arthrodesis were divided into two groups according to the used materials: 6.5 mm cannulated screw (A) and anterior fusion plate (B). The clinical scores were compared between groups. The radiologic results were then assessed by union time. The results were statistically analyzed using SPSS 20. Results: There was no significant difference between both groups in the American Orthopedic Foot & Ankle Society (AOFAS) score (p = 0.75), and in the visual analog scale (p = 0.42). In group B, two cases included wound infection at the surgical site. In tt A, the mean union time was 10.5 ± 2.3 weeks. In group B, it was 7.8 ± 1.3. There was a statistically significant difference (p = 0.007) between union time in both groups. Conclusion: Anterior fusion plate is an effective method for shorter union time, but the surgeon should be careful with the surgical wound at the skin incision site in the lesion of the distal tibia. Level of Evidence III, Retrospective comparative study.

RESUMO Objetivo: Comparar os resultados clínicos e radiológicos assim como as complicações de pacientes sujeitos a artrodese de abordagem transfibular com o uso de parafuso canulado ou placa óssea anterior. Métodos: Pacientes sujeitos a artrodese do tornozelo foram divididos em dois grupos de acordo com os materiais usados: parafuso canulado de 6,5 mm (A) e placa óssea anterior (B). Os escores clínicos de ambos os grupos foram comparados e os resultados radiológicos foram avaliados de acordo com o tempo de união óssea. Os resultados foram analisados estatisticamente usando SPSS 20. Resultados: Não houve diferença significativa entre os grupos quanto ao escore American Orthopedic Foot & Ankle Society (AOFAS) (p = 0,75) e a escala visual analógica (p = 0,42). No grupo B, ocorreu infecção na área da cirurgia em dois casos. No grupo A, a média de tempo de união foi de 10,5 ± 2,3 semanas. No grupo B, este foi de 7,8 ± 1,3. Constatou-se diferença estatisticamente significante (p = 0,007) quanto ao tempo de união em ambos os grupos. Conclusão: Os autores concluíram que a placa óssea anterior é um método eficiente para tempos de união curtos, porém o cirurgião deve ficar atento à ferida cirúrgica na área de incisão da pele em casos de lesão na tíbia distal. Nível de Evidência III, Estudo retrospectivo comparativo.

Renal protective effects of vicenin-2 and scolymoside in a mouse model of sepsis

This study was initiated to determine whether 2 structurally related flavonoids found in Cyclopia subternata-vicenin-2 (VCN) and scolymoside (SCL)-could modulate renal functional damage in a mouse model of sepsis, and to elucidate the relevant underlying mechanisms. The potential of VCN and SCL treatment to reduce renal damage induced by cecal ligation and puncture (CLP) surgery in mice was measured via assessment of serum creatinine, blood urea nitrogen (BUN), lipid peroxidation, total glutathione, glutathione peroxidase activity, catalase activity, and superoxide dismutase activity. Treatment with either VCN or SCL resulted in elevated plasma levels of BUN and creatinine, and of protein in the urine of mice with CLP-induced renal damage. Moreover, both VCN and SCL inhibited nuclear factor κB activation and reduced the induction of nitric oxide synthase and excessive production of nitric acid. VCN and SCL treatment also reduced the plasma levels of interleukin-6, and tumor necrosis factor-α, reduced lethality due to CLP-induced sepsis, increased lipid peroxidation, and markedly enhanced the antioxidant defense system by restoring the levels of superoxide dismutase, glutathione peroxidase, and catalase in kidney tissues. The present results suggest that VCN and SCL protect mice from sepsis-triggered renal injury