The effects of single versus combined therapy using LIM-kinase 2 inhibitor and type 5 phosphodiesterase inhibitor on erectile function in a rat model of cavernous nerve injury-induced erectile dysfunction / 亚洲男科学杂志(英文版)

We aimed to determine whether combination of LIM-kinase 2 inhibitor (LIMK2i) and phosphodiesterase type-5 inhibitor (PDE5i) could restore erectile function through suppressing cavernous fibrosis and improving cavernous apoptosis in a rat model of cavernous nerve crush injury (CNCI). Seventy 12-week-old Sprague-Dawley rats were equally distributed into five groups as follows: (1) sham surgery (Group S), (2) CNCI (Group I), (3) CNCI treated with daily intraperitoneal administration of 10.0 mg kg-1 LIMK2i (Group I + L), (4) daily oral administration of 20.0 mg kg-1 udenafil, PDE5i (Group I + U), and (5) combined administration of 10.0 mg kg-1 LIMK2i and 20.0 mg kg-1 udenafil (Group I + L + U). Rats in Groups I + L, I + U, and I + L + U were treated with respective regimens for 2 weeks after CNCI. At 2 weeks after surgery, erectile response was assessed using electrostimulation. Penile tissues were processed for histological studies and western blot. Group I showed lower intracavernous pressure (ICP)/mean arterial pressure (MAP), lower area under the curve (AUC)/MAP, decreased immunohistochemical staining for alpha-smooth muscle (SM) actin, higher apoptotic index, lower SM/collagen ratio, increased phospho-LIMK2-positive fibroblasts, decreased protein kinase B/endothelial nitric oxide synthase (Akt/eNOS) phosphorylation, increased LIMK2/cofilin phosphorylation, and increased protein expression of fibronectin, compared to Group S. In all three treatment groups, erectile responses, protein expression of fibronectin, and SM/collagen ratio were improved. Group I + L + U showed greater improvement in erectile response than Group I + L. SM content and apoptotic index in Groups I + U and I + L + U were improved compared to those in Group I. However, Group I + L did not show a significant improvement in SM content or apoptotic index. The number of phospho-LIMK2-positive fibroblasts was normalized in Groups I + L and I + L + U, but not in Group I + U. Akt/eNOS phosphorylation was improved in Groups I + U and I + L + U, but not in Group I + L. LIMK2/cofilin phosphorylation was improved in Groups I + L and I + L + U, but not in Group I + U. Our data indicate that combined treatment of LIMK2i and PDE5i immediate after CN injury could improve erectile function by improving cavernous apoptosis or eNOS phosphorylation and suppressing cavernous fibrosis. Rectification of Akt/eNOS and LIMK2/cofilin pathways appears to be involved in their improvement.

Role of inhibiting LIM-kinase2 in improving erectile function through suppression of corporal fibrosis in a rat model of cavernous nerve injury / 亚洲男科学杂志(英文版)

We evaluated whether LIM-kinase 2 inhibitor (LIMK2i) could improve erectile function by suppressing corporal fibrosis through the normalization of the Rho-associated coiled-coil protein kinase 1 (ROCK1)/LIMK2/Cofilin pathway in a rat model of cavernous nerve crush injury (CNCI). Sixty 11-week-old male Sprague-Dawley rats were divided equally into five groups: sham surgery (S), CNCI (I), and CNCI treated with low-dose (L), medium-dose (M), and high-dose (H) LIMK2i. The L, M, and H groups were treated with a daily intraperitoneal injection of LIMK2i (2.5, 5.0, and 10.0 mg kg-1 body weight, respectively) for 1 week after surgery. The erectile response was assessed using electrostimulation at 1 week, postoperatively. Penile tissues were processed for Masson's trichrome staining, double immunofluorescence, and Western blot assay. Erectile responses in the H group improved compared with the I group, while the M group showed only partial improvement. A significantly decreased smooth muscle/collagen ratio and an increased content of fibroblasts positive for phospho-LIMK2 were noted in the I group. The M and H groups revealed significant improvements in histological alterations and the dysregulated LIMK2/Cofilin pathway, except for LIMK2 phosphorylation in the M group. The inhibition of LIMK2 did not affect the ROCK1 protein expression. The content of fibroblasts positive for phospho-LIMK2 in the H group returned to the level found in the S group, whereas it did not in the M group. However, the L group did not exhibit such improvements. Our data suggest that the inhibition of LIMK2, particularly with administration of 10.0 mg kg-1 body weight LIMK2i, can improve corporal fibrosis and erectile function by normalizing the LIMK2/Cofilin pathway.

Role of Jun amino-terminal kinase (JNK) in apoptosis of cavernosal tissue during acute phase after cavernosal nerve injury / 亚洲男科学杂志(英文版)

The present study aimed to identify which mitogen-activated protein kinase (p38 or Jun amino-terminal kinase [JNK]) was involved in cavernosal apoptosis during the acute phase after cavernosal nerve crush injury (CNCI) in rats to ameliorate apoptosis of cavernosal tissue, such as smooth muscle (SM). A total of twenty 10-week-old male Sprague-Dawley rats were divided equally into two groups: sham surgery (S) and CNCI (I). The I group approximated the clinical situation of men undergoing radical prostatectomy using two 60-second compressions of both CNs with a microsurgical vascular clamp. At 2-week postinjury, erectile response was assessed using electrostimulation. Penile tissues were harvested for immunohistochemistry analysis of alpha-SM actin (α-SMA), western blot analysis, and double immunofluorescence analysis of α-SMA and phosphorylated p38 or JNK, as well as double immunofluorescent of TUNEL and phosphorylated p38 or JNK. At 2-week postinjury, the I group had a significantly lower intracavernous pressure (ICP)/mean arterial pressure (MAP) and a lower area under the curve (AUC)/MAP than the S group. The I group also exhibited decreased immunohistochemical staining of α-SMA, an increase in the number of SM cells positive for phosphorylated JNK, an increased number of apoptotic cells positive for phosphorylated JNK, and increased JNK phosphorylation compared with the S group. However, there was no significant difference in p38 phosphorylation expression or the number of SM cells positive for phosphorylated p38 between the two groups. In conclusion, our data suggest that JNK, not p38, is involved in cavernosal apoptosis during the acute phase after partial CN damage.

Infraclavicular topography of the brachial plexus fascicles in different upper limb positions / Topografía infraclavicular de los fascículos del plexo braquial en diferentes posiciones del miembro superior

Brachial plexus neuropathies are common complaints among patients seen at orthopedic clinics. The causes range from traumatic to occupational factors and symptoms include paresthesia, paresis, and functional disability of the upper limb. Treatment can be surgical or conservative, but detailed knowledge of the brachial plexus is required in both cases to avoid iatrogenic injuries and to facilitate anesthetic block, preventing possible vascular punctures. Therefore, the objective of this study was to evaluate the topography of the infraclavicular brachial plexus fascicles in different upper limb positions adopted during some clinical procedures. A formalin-preserved, adult, male cadaver was used. The infraclavicular and axillary regions were dissected and the distance of the brachial plexus fascicles from adjacent bone structures was measured. No anatomical variation in the formation of the brachial plexus was observed. The metric relationships between the brachial plexus and adjacent bone prominences differed depending on the degree of shoulder abduction. Detailed knowledge of the infraclavicular topography of neurovascular structures helps with the diagnosis and especially with the choice of conservative or surgical treatment of brachial plexus neuropathies.

Las neuropatías del plexo braquial son quejas comunes entre los pacientes atendidos en las clínicas ortopédicas. Las causas van desde traumas a factores ocupacionales y los síntomas incluyen parestesias, paresia e incapacidad funcional del miembro superior. El tratamiento puede ser quirúrgico o conservador, pero se requiere un conocimiento detallado del plexo braquial en ambos casos para evitar lesiones iatrogénicas y para facilitar el bloqueo anestésico, evitando posibles lesiones vasculares. Por lo tanto, el objetivo de este estudio fue evaluar la topografía de los fascículos del plexo braquial infraclavicular en diferentes posiciones de los miembros superiores adoptadas durante algunos procedimientos clínicos. Se llevó a cabo la disección de las regiones infraclavicular y axilar de un cadáver adulto, de sexo masculino, conservado en formaldehído. Se midió la distancia de los fascículos del plexo braquial en relación a las estructuras óseas adyacentes. No se observó variación anatómica en la formación del plexo braquial. Las relaciones métricas entre el plexo braquial y las prominencias óseas adyacentes difieren en función del grado de abducción del hombro. El conocimiento detallado de la topografía infraclavicular de las estructuras neurovasculares ayuda con el diagnóstico y sobre todo con la elección del tratamiento conservador o quirúrgico de las neuropatías del plexo braquial.

Effect of amnion-wrapped allogenic nerve bridging on peripheral nerve injury / Efecto del puente alogénico de nervio envuelto en membrana amniótica sobre la lesión de nervio periférico

This work aims to investigate the effect of fetal amnion-wrapped acellular allogenic nerve transplantation on peripheral nerve injury (PNI) in dogs and to explore its advantages and feasibility in PNI repair. A total of 15 dogs were divided into three groups: the allogenic nerve transplantation (A), amnion-wrapped allogenic nerve transplantation (B), and allogenic nerve donor (C) groups. Neurite counts after myelin and H-E stainings, soleus muscle action potentials, and sciatic nerve conductive velocities were compared between the A and B groups at 16 w after operation. The B group showed better nerve regeneration than the A group at 16 w. Compared with the A group, the B group showed a better growth continuity of the transplanted nerve and milder inflammatory reactions around the nerve. The B group presented much more proliferated Schwannocytes and regenerated nerve fibers than the A group. The neurite density and the amplitude of the soleus muscle action potentials in the B group were significantly higher than those in the A group (P < 0.05). The two groups did not show significant differences in nerve conductive velocities (P > 0.05). Amnion-wrapped acellular allogenic nerve transplantation can improve defected nerve morphology and the quality of transplanted nerve regeneration.

El objetivo fue investigar el efecto del trasplante alogénico de nervio acelular envuelto en membrana amniótica fetal sobre la lesión del nervio periférico (LNP) en perros, y explorar sus ventajas y viabilidad en la reparación de LNP. Quince 15 perros se dividieron en tres grupos: grupo trasplante alogénico de nervio (A), grupo trasplante alogénico de nervio envuelto en membrana amniótica (B), y grupo donante alogénico de nervio (C). Se compararon el recuento de neuritas posterior a la tinción de hematoxilina-eosina (HE) y para mielina, potenciales de acción del músculo sóleo, y velocidades conductoras nerviosas del nervio ciático entre los grupos A y B, 16 semanas después de la operación. El grupo B mostró una mejor regeneración de los nervios que el grupo A a las 16 semanas. En comparación con el grupo A, el grupo B mostró una mejor continuidad del crecimiento del nervio trasplantado con reacciones inflamatorias leves alrededor del nervio. El grupo B presentó fibras nerviosas donde proliferaron más los Schwannocitos y regeneración que el grupo A. La densidad de las neuritas y la amplitud de los potenciales de acción del músculo sóleo en el grupo B fueron significativamente más altos (p <0,05). Ambos grupos no mostraron diferencias significativas en las velocidades conductoras nerviosas (P> 0,05). El trasplante alogénico de nervio acelular envuelto en membrana amniótica puede mejorar la morfología del nervio lesionado y la calidad de regeneración del nervio trasplantado.