Effects of Oral Pirfenidone on Colon Anastomosis Healing and Adhesion Formation in Rats.

INTRODUCTION: Many experimental studies have examined multiple drugs or treatments to improve the healing of intestinal anastomoses. Synthetic prostacyclin analogs, immunosuppressants, erythropoietin, growth hormone, insulin-like growth factor type 1, synthetic metalloproteinases inhibitors, and hyperbaric oxygen therapy have produced promising results in low-risk models of anastomosis dehiscence. However, in high-risk models, only hyperbaric oxygen therapy has been shown to be useful. Pirfenidone (PFD), a commonly used antifibrosing drug, has not been shown to be effective for this purpose. Our objective was to evaluate the effects of PFD on anastomosis healing and adhesion genesis in a low-risk rat model of dehiscence of colonic anastomosis. METHODS: An experimental study was conducted on 40 healthy Wistar rats randomly assigned to the control group or PFD experimental group (20 rats in each group). Colon anastomosis was performed 3 cm above the peritoneal reflection using the same technique in all animals. Mechanical resistance was studied by measuring bursting pressure. Adhesions were evaluated macroscopic and histologically using common staining techniques. Animals received the first PFD dose 12 h after surgery at a dose of 500 mg/kg one a day (SID) for 5 consecutive days. On day 6, the animals were reoperated on to measure the bursting pressure in situ and to classify adhesions macroscopically, and the anastomosed colon was resected for histological analysis. RESULTS: There were no deaths, complications, or anastomosis dehiscence in either group. The mean bursting pressure was 120.8 ± 11 mm Hg and 135.5 ± 12.4 in the control and PFD groups, respectively (p < 0.001). The adhesions were less dense and had less inflammatory cell infiltration in the PFD group (p < 0.02 and 0.002, respectively). Collagen content was slightly higher in the PFD group (p = 0.04). CONCLUSIONS: Our results revealed favorable effects of PFD in this low-risk colon anastomosis model; for example, the bursting pressure was higher, and the macroscopic adhesions were soft and exhibited less inflammatory infiltration and higher collagen content in the PFD group than in the control group. The results showing that PFD treatment was associated with better healing of minor adhesions seem to be paradoxical because the therapeutic indications for this drug are directed at treating fibrosing diseases.

High-Frequency Neuronal Bursting is Essential for Circadian and Sleep Behaviors in Drosophila.

Circadian rhythms have been extensively studied in Drosophila; however, still little is known about how the electrical properties of clock neurons are specified. We have performed a behavioral genetic screen through the downregulation of candidate ion channels in the lateral ventral neurons (LNvs) and show that the hyperpolarization-activated cation current Ih is important for the behaviors that the LNvs influence: temporal organization of locomotor activity, analyzed in males, and sleep, analyzed in females. Using whole-cell patch clamp electrophysiology we demonstrate that small LNvs (sLNvs) are bursting neurons, and that Ih is necessary to achieve the high-frequency bursting firing pattern characteristic of both types of LNvs in females. Since firing in bursts has been associated to neuropeptide release, we hypothesized that Ih would be important for LNvs communication. Indeed, herein we demonstrate that Ih is fundamental for the recruitment of pigment dispersing factor (PDF) filled dense core vesicles (DCVs) to the terminals at the dorsal protocerebrum and for their timed release, and hence for the temporal coordination of circadian behaviors.SIGNIFICANCE STATEMENT Ion channels are transmembrane proteins with selective permeability to specific charged particles. The rich repertoire of parameters that may gate their opening state, such as voltage-sensitivity, modulation by second messengers and specific kinetics, make this protein family a determinant of neuronal identity. Ion channel structure is evolutionary conserved between vertebrates and invertebrates, making any discovery easily translatable. Through a screen to uncover ion channels with roles in circadian rhythms, we have identified the Ih channel as an important player in a subset of clock neurons of the fruit fly. We show that lateral ventral neurons (LNvs) need Ih to fire action potentials in a high-frequency bursting mode and that this is important for peptide transport and the control of behavior.

Effects of Aloe Vera on healing of colonic anastomoses: experimental rat study / Efeitos da Aloe Vera na cicatrização de anastomoses colônicas: estudo experimental em ratos

ABSTRACT Background: Although herbal medicinal products are being used widely throughout the World, beneficial and harmful effects have not been well documented. Our aim was to evaluate the effects of Aloe Vera (AV) on colonic anastomosis healing. Material and methods: 112 albino Wistar rats were randomly assigned into five main groups: preoperative Aloe Vera Group (P), pre- and postoperative Aloe Vera Group (PP), Control Group (C), sham Aloe Vera Group (SA) and Sham Control Group (SC). Groups P, PP, and SA received 1.6 mL/kg per day Aloe Vera by orogastric feeding catheter for 1 month prior to the experiment. Groups P, PP, and C underwent anastomosis of the distal colon, and subgroups (n = 4) of each were sacrificed on postoperative day 3, 7, 14 and 21. Anastomotic bursting pressure, perianastomotic collagen content and histopathological changes were studied. Results: The SC Group had significantly higher ABP when compared with the SA Group (p = 0.0002), although hydroxyproline content showed no difference. When ABP was compared between anastomosis groups, it was found significantly lower in Aloe Vera groups on Day 3 (P3 vs. C3, p = 0.003 and PP3 vs. C3, p = 0.007). Hydroxyproline content was significantly lower in Group PP than Group C, also on Day 3 (p = 0.05). Significant difference was not detected after Day 3 in any of the study parameters. Conclusion: Aloe Vera decreased tissue collagen content in the early postoperative period. It is advisable to call into question the concomitant usage of conventional medicine and the herbal supplements for the surgeons in their clinical practice.

RESUMO Fundamentação: Embora os medicamentos à base de plantas sejam amplamente utilizados no mundo inteiro, seus efeitos (benéficos e prejudiciais) não estão bem documentados. Este estudo teve como objetivo avaliar os efeitos da Aloe vera (AV) na cicatrização de anastomoses colônicas. Material e métodos: 112 ratos Wistar albinos foram distribuídos aleatoriamente em cinco grupos principais: AV pré-operatório (P), AV pré e pós-operatório (PP), controle (C), sham AV (SA) e sham controle (SC). Os grupos P, PP e SA receberam AV em uma dose de 1,6 mL/kg por dia por sonda de alimentação orogástrica por 1 mês antes do experimento. Os grupos P, PP e C foram submetidos a anastomose do cólon distal. Subgrupos (n = 4) de cada grupo foram sacrificados no terceiro, sétimo, 14° e 21° dias pós-operatórios. Os seguintes parâmetros foram avaliados: pressão de ruptura anastomótica (PRA), conteúdo de colágeno perianastomótico e alterações histopatológicas. Resultados: O grupo SC apresentou PRA significativamente maior quando comparado ao grupo SA (p = 0,0002), embora o conteúdo de hidroxiprolina não tenha apresentado diferença. Ao comparar a PRA entre os grupos de anastomose, ela foi significativamente menor no terceiro dia nos grupos que usaram AV (P3 vs. C3, p = 0,003 e PP3 vs. C3, p = 0,007). No terceiro dia, o teor de hidroxiprolina foi significativamente menor no grupo PP do que no grupo C (p = 0,05). Após o terceiro dia, não se observou diferença significativa em nenhum dos parâmetros do estudo. Conclusão: O uso de AV diminuiu o conteúdo de colágeno tecidual no período pós-operatório imediato. É aconselhável questionar o uso concomitante da medicina convencional e suplementos fitoterápicos na prática clínica.

Robust and tunable bursting requires slow positive feedback.

We highlight that the robustness and tunability of a bursting model critically rely on currents that provide slow positive feedback to the membrane potential. Such currents have the ability to make the total conductance of the circuit negative in a timescale that is termed "slow" because it is intermediate between the fast timescale of the spike upstroke and the ultraslow timescale of even slower adaptation currents. We discuss how such currents can be assessed either in voltage-clamp experiments or in computational models. We show that, while frequent in the literature, mathematical and computational models of bursting that lack the slow negative conductance are fragile and rigid. Our results suggest that modeling the slow negative conductance of cellular models is important when studying the neuromodulation of rhythmic circuits at any broader scale. NEW & NOTEWORTHY Nervous system functions rely on the modulation of neuronal activity between different rhythmic patterns. The mechanisms of this modulation are still poorly understood. Using computational modeling, we show the critical role of currents that provide slow negative conductance, distinct from the fast negative conductance necessary for spike generation. The significance of the slow negative conductance for neuromodulation is often overlooked, leading to computational models that are rigid and fragile.

Hyperpolarization-Activated Current Induces Period-Doubling Cascades and Chaos in a Cold Thermoreceptor Model.

In this article, we describe and analyze the chaotic behavior of a conductance-based neuronal bursting model. This is a model with a reduced number of variables, yet it retains biophysical plausibility. Inspired by the activity of cold thermoreceptors, the model contains a persistent Sodium current, a Calcium-activated Potassium current and a hyperpolarization-activated current (Ih) that drive a slow subthreshold oscillation. Driven by this oscillation, a fast subsystem (fast Sodium and Potassium currents) fires action potentials in a periodic fashion. Depending on the parameters, this model can generate a variety of firing patterns that includes bursting, regular tonic and polymodal firing. Here we show that the transitions between different firing patterns are often accompanied by a range of chaotic firing, as suggested by an irregular, non-periodic firing pattern. To confirm this, we measure the maximum Lyapunov exponent of the voltage trajectories, and the Lyapunov exponent and Lempel-Ziv's complexity of the ISI time series. The four-variable slow system (without spiking) also generates chaotic behavior, and bifurcation analysis shows that this is often originated by period doubling cascades. Either with or without spikes, chaos is no longer generated when the Ih is removed from the system. As the model is biologically plausible with biophysically meaningful parameters, we propose it as a useful tool to understand chaotic dynamics in neurons.

Tratamiento quirúrgico de las fracturas por estallamiento de columna toracolumbar / Traitement chirurgical des fractures-éclatement du rachis thoracolombaire

Introducción: las fracturas vertebrales constituyen un grave problema de salud, la zona toracolumbar constituye la localización más frecuente. El tratamiento quirúrgico, en fracturas por estallamiento, parece el de mejores resultados pero presenta la disyuntiva de si a todos los pacientes se les debe realizar fusión. Objetivo: mostrar los resultados obtenidos a los dos años con el tratamiento quirúrgico de las fracturas por estallamiento de columna toracolumbar, en los servicios de Ortopedia y Neurocirugía del Hospital Calixto García entre enero de 2011 y julio de 2013. Método: estudio descriptivo prospectivo en pacientes con diagnóstico de fracturas toracolumbares por estallamiento tratados quirúrgicamente, asociando en algunos a la fijación, la fusión. Las variables estudiadas: edad, sexo, mecanismo causal, localización, tipo de fractura, deformidad cifótica y altura del cuerpo vertebral. El índice de Oswestry y la Escala Visual Analógica del dolor, medidos antes y dos años después de la intervención, fueron los instrumentos evaluadores empleados. Resultados: serie constituida por 28 pacientes, predominaron el sexo masculino, y el accidente automovilístico como mecanismo causal; la localización más frecuente fue en el segmento T11-L2 para las fracturas tipo A3 y A4 según AO; las variaciones de deformidad cifótica y altura del cuerpo vertebral fueron muy semejantes a los dos años entre pacientes con fusión y sin ella. El índice de Oswestry y la Escala Visual Analógica del dolor mostraron significativa mejoría. Conclusiones: los resultados radiográficos y funcionales fueron similares en pacientes con fusión y sin ella. La fusión posterior no necesita ser un procedimiento de rutina en fracturas por estallamiento de columna toracolumbar(AU)

Introduction: vertebral fractures are serious health problem; the thoracolumbar zone is the most frequent location. Surgical treatment in explant fractures seems to be the one with the best results but presents the dilemma of whether all patients should be fusion. Objective: show the results obtained at two years with the surgical treatment of thoracolumbar spine fractures in Orthopedics and Neurosurgery services at Calixto García Hospital from January 2011 to July 2013. Method: prospective descriptive study was carried out in patients with diagnosis of surgically treated thoracolumbar fractures, associated to fixation, fusion. The variables studied were age, sex, causal mechanism, location, type of fracture, kyphotic deformity and vertebral body height. The Oswestry Index and Visual Analog Pain Scale, measured before and two years after the intervention, were the evaluation instruments used. Results: twenty-eight patients formed this series, the male sex predominated, and automobile accident was a causal mechanism. The most frequent location was segment T 11- L 2 for fractures type A 3 and A 4 according to AO. The variations of kyphotic deformity and height of the vertebral body were very similar after two years in patients with and without fusion. Oswestry Index and Visual Analog Pain Scale showed significant improvement. Conclusions: radiographic and functional results were similar in patients with and without fusion. Post fusion does not need to be a routine procedure in thoracolumbar collapse fractures (AU)

Introduction: les fractures vertébrales, étant plus fréquemment localisées dans la région thoracolombaire, constituent un sérieux problème de santé. Le traitement chirurgical des fractures-éclatement semble être le meilleur étant donnés ses résultats, mais il pose un question -est-ce que tous les patients doivent subir une fusion? Objectif: l'objectif de cette étude est de montrer les résultats obtenus deux ans après le traitement chirurgical des fractures-éclatement thoracolombaires aux services d'orthopédie et de neurochirurgie, à l'hôpital "Calixto García" entre janvier 2011 et juillet 2013. Méthode: une étude descriptive et prospective des patients diagnostiqués et traités chirurgicalement pour des fractures-éclatement thoracolombaires, associant la fixation et la fusion dans certains cas, a été effectuée. Des variables telles que l'âge, le sexe, les causes, la localisation, le type de fracture, la déformation cyphotique, et la taille du corps vertébral ont été aussi étudiées. L'indice d'Oswestry et l'échelle visuelle analogique de la douleur ont été les outils d'évaluation utilisés auparavant et deux ans après l'opération. Résultats: dans une série de 28 patients, ce sont les hommes le plus souvent touchés, tandis que l'accident de voiture a été la cause la plus fréquemment trouvée ; les fractures type A3 et A4, selon AO, se sont souvent localisées au niveau du segment T11-L2 ; les variations de la déformation cyphotique et la taille du corps vertébral ont été très similaires au bout de deux ans chez les patients ayant subi ou pas une fusion. L'indice d'Oswestry et l'échelle visuelle analogique de la douleur ont montré une amélioration significative. Conclusions: les résultats radiologiques et fonctionnels ont été similaires chez les patients ayant subi ou pas une fusion. La fusion postérieure n'est pas nécessairement un procédé habituel dans les fractures-éclatement du rachis thoracolombaire (AU)

Phase synchronization of coupled bursting neurons and the generalized Kuramoto model.

Bursting neurons fire rapid sequences of action potential spikes followed by a quiescent period. The basic dynamical mechanism of bursting is the slow currents that modulate a fast spiking activity caused by rapid ionic currents. Minimal models of bursting neurons must include both effects. We considered one of these models and its relation with a generalized Kuramoto model, thanks to the definition of a geometrical phase for bursting and a corresponding frequency. We considered neuronal networks with different connection topologies and investigated the transition from a non-synchronized to a partially phase-synchronized state as the coupling strength is varied. The numerically determined critical coupling strength value for this transition to occur is compared with theoretical results valid for the generalized Kuramoto model.

Can LigaSure™ be used to perform sleeve gastrectomy? - Tensile strength and histological changes.

INTRODUCTION: LigaSure™ was developed as an alternative to suture ligatures, hemoclips and staplers for ligating vessels and tissue bundles. The aim of the present study was to determine whether LigaSure can be used as a welding instrument in the performance of laparoscopic sleeve gastrectomy. MATERIAL AND METHODS: Gastric specimens were assigned into four groups. Group 1 - specimens remained with the staple line intact. Group 2 - the staple line was oversewn. Group 3 - the staple line was resected with LigaSure. Group 4 - staple line was resected with LigaSure and the seal was oversewn. In all specimens the pressure tolerance was assessed using a portable sensor. RESULTS: In group 1 the leak pressure was 34.7 ± 11.7 whereas in group 2 specimens the pressure increased three-fold (101.9 ± 21.4). The LigaSure seal alone (group 3) achieved a mean pressure of 13.7 mmHg. However, in group 4 there was an exponential increase on their burst strength up to 142 mmHg (p = 0.0005). CONCLUSION: According to our results, LigaSure could be used to perform laparoscopic sleeve gastrectomy with reduction of staple-line bleeding and, when reinforced with a running suture, it achieves a strength that approaches that of staples plus oversewing.

A brief history of excitable map-based neurons and neural networks.

This review gives a short historical account of the excitable maps approach for modeling neurons and neuronal networks. Some early models, due to Pasemann (1993), Chialvo (1995) and Kinouchi and Tragtenberg (1996), are compared with more recent proposals by Rulkov (2002) and Izhikevich (2003). We also review map-based schemes for electrical and chemical synapses and some recent findings as critical avalanches in map-based neural networks. We conclude with suggestions for further work in this area like more efficient maps, compartmental modeling and close dynamical comparison with conductance-based models.

Efeitos da irradiação com raios-X em anastomoses colônicas: estudo estereológico experimental em ratos

PURPOSE: This study was done in order to quantify changes on bursting pressure and collagen content on irradiated colon anastomosis. METHODS: Twelve Wistar rats were submitted to colon section and anastomosis. Animals were divided in two groups: An (control, n=7) and I+An (irradiated, n=5). An group was submitted only to surgery while I+An received a single dose irradiation (1096 cGy) seven days before operation. Animals were sacrificed on seventh postoperative day to quantify anastomosis bursting pressure and collagen content. Collagen quantification was done by vertical section stereology. RESULTS: An group present higher values of anastomosis bursting pressure (172 mm Hg X 60 mm Hg, p = 0,004) and collagen content (14,24 X 1,62, p = 0,004) as compared to I+An group. On An group the site of colon rupture was more frequently found on the perianastomotic area while on I+An group the rupture was mainly on anastomotic line (p = 0,007). CONCLUSION: Irradiation impaired anastomotic healing as evidenced by reduction of anastomotic bursting pressure and collagen content on irradiated animals.

OBJETIVO: Este estudo foi realizado para quantificar possíveis alterações na tensão de ruptura e na concentração de colágeno em anastomoses realizadas em cólon irradiado. MÉTODOS: Doze ratos Wistar foram submetidos a secção e anastomose do cólon, constituindo dois grupos: An (controle, n=7) e I+An (irradiado, n=5). O grupo An foi submetido apenas à cirurgia enquanto o grupo I+An recebeu dose única de irradiação (1096 cGy) 7 dias antes da operação. Todos foram sacrificados no sétimo dia pós-operatório, para verificação da tensão de ruptura da anastomose e quantificação do colágeno. A quantificação do colágeno foi feita por estereologia de cortes verticais. RESULTADOS: O grupo An apresentou valores superiores ao grupo I+An quando comparados a pressão de ruptura da anastomose (172 mm Hg X 60 mm Hg, p = 0,004) e o índice de colágeno (14,24 X 1,62, p = 0,004). No grupo An o local de ruptura do cólon ocorreu com maior freqüência na área perianastomótica, enquanto que no grupo I+An a ruptura ocorreu com maior freqüência na linha anastomótica (p = 0,007). CONCLUSÃO: A irradiação prejudicou a cicatrização anastomótica, conforme evidenciado pela diminuição da pressão de ruptura da anastomose e do índice de colágeno no grupo de animais irradiados.