Basic anatomical investigation of semitendinosus and the long head of biceps femoris muscle for their possible use in electrically stimulated neosphincter formation

Summary Anal neosphincter formation with electrically stimulated gracilis muscle is used increasingly for the surgical treatment of fecal incontinence. An alternative to gracilis might be of interest if this muscle is not available. 30 semitendinosus muscles and 15 long heads of biceps femoris were investigated on human cadavers. In particular, the nerve and vascular supply of these muscles was studied, both representing basic factors for muscle transposition. The long head of biceps femoris m. was found to receive its dominant vascular supply from the first and second perforating artery and its nerve supply from one motor branch out of the sciatic nerve, both as described in literature. The examination of semitendinosus m., however, revealed new anatomical aspects in its vascular supply. In all cases semitendinosus m. was found to receive dominant vascular pedicles from the medial circumflex femoral artery close to the ischial tuberosity and the second perforating artery. The nerve supply consisted of two motor branches out of the sciatic nerve. Both muscles fulfilled several basic criterias for transposition to the anus. However, regarding these requirements, semitendinosus offered distinct advantages in comparison with the long head of biceps femoris. Due to its vascular and nerve topography, semitendinosus seems suitable to serve as an alternative to gracilis.

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Bases anatomiques de l'utilisation du muscle semitendineux et du chef long du biceps fémoral comme néosphincter anal électro-stimulé

Résumé La graciloplastie électro-stimulée est utilisée de plus en plus fréquemment dans le traitement chirurgical de l'incontinence anale. L'utilisation d'un autre muscle peut être intéressante si le muscle gracile n'est pas utilisable. 30 muscles semitendineux et 15 longs chefs du biceps fémoral ont été étudiés sur des cadavres humains. Ce travail a porté particulièrement sur l'innervation et la vascularisation de ces muscles, dont dépendent les possibilités de transposition. Le long chef du m. biceps fémoral recevait sa vascularisation principale de la première et de la deuxième artère perforante et son innervation d'une branche motrice venant du nerf sciatique, tel que cela est décrit dans la littérature. L'étude du m. semitendineux a montré de nouveaux aspects anatomiques dans sa vascularisation. Dans tous les cas ce muscle recevait sa vascularisation principale de l'artère circonflexe médiale près de la tubérosité ischiatique et de la deuxième a. perforante. Son innervation venait de deux branches motrices du nerf sciatique. Ces deux muscles répondaient aux critères nécessaires pour leur transposition comme néo sphincter. Cependant, compte-tenu de sa vascularisation et de son innervation, le m. semitendineux répond mieux aux impératifs anatomiques que le long chef du biceps et représente une alternative au muscle gracile pour la création d'un néo sphincter anal.

     

Bromodomain inhibitor I‐BET151 suppresses immune responses during fungal–immune interaction

Changes in the epigenetic landscape of immune cells are a crucial component of gene activation during the induction of inflammatory responses, therefore it has been hypothesized that epigenetic modulation could be employed to restore homeostasis in inflammatory scenarios. Fungal pathogens cause a large burden of morbidity and even mortality due to the hyperinflammatory processes that induce mucosal, allergic or systemic infections. Bromodomain and extraterminal domain (BET) proteins are considered as one as the most tantalizing pharmacological targets for the modulation of inflammatory responses at the epigenetic level. Nothing is known of the role of BET inhibitors on the inflammation induced by fungal pathogens. In the present study, we assessed the in vitro efficacy of the small molecular histone mimic BET inhibitor I‐BET151 to modulate innate immune responses during fungal–immune interaction with the clinically relevant fungal pathogens Candida albicans and Aspergillus fumigatus. Our results prove that BET inhibitors (I‐BETs) represent an important modulator of inflammation induced by fungal pathogens: both direct production of proinflammatory cytokines and the induction of trained immunity were inhibited by I‐BET151. These modulatory effects are likely to have important potential implications in clinically relevant situations.     

The influence of the donor nerve on the function and morphology of a mimic muscle after cross innervation: an experimental study in rabbits.

In the present study we used the scutuloauricularis muscle in the rabbit to investigate the functional and morphometric alterations in the mimic-muscle system after cross-reinnervation. The scutuloauricularis muscle is the first experimental model that allows functional assessment of a mimic muscle by force measurements. A total of 36 rabbits were separated into three groups. In group 1 the scutuloauricularis nerve was cut and re-sutured to itself to achieve self-reinnervation; in group 2 the buccal nerve was used to cross-reinnervate the fast scutuloauricularis muscle and in group 3 the slow buccinator muscle was cross-reinnervated by the scutuloauricularis nerve. After a period of 6 months the maximal tetanic tensions of the reinnervated scutuloauricularis muscles were determined and histomorphometric examinations of muscle and nerve biopsies were carried out. Force measurements showed no loss of muscle force after self- and cross-reinnervation. The normal scutuloauricularis muscle contained 33%, and the buccinator muscle 46%, slow type I fibres. After self-reinnervation of the scutuloauricularis muscle the fibre-type composition remained unchanged. After cross-reinnervation we saw a significant fast-to-slow transformation of the scutuloauricularis muscle and a significant slow-to-fast transformation of the buccinator muscle. The number of myelinated nerve fibres in the scutuloauricularis nerve increased after cross-reinnervation from 1531 to 4077 (group 2) and to 3813 (group 3). The number of nerve fibres in the buccal nerve (3209) was unchanged after cross-reinnervation. The results of the present study might be relevant in the treatment of irreversible facial palsy by functional muscle transplantation and cross-face nerve grafting. The facial nerve branch used for cross-reinnervation seems to determine the functional outcome.     

The impact of a muscle target organ on nerve grafts with different lengths—A histomorphological analysis

The present study was done in order to evaluate the influence of a target muscle on the regenerative processes in long nerve grafts. In 21 rabbits the saphenous nerve was used as a nerve graft and coapted to the cut motor nerve of vastus medialis. The animals were separated into three groups with different graft lengths, namely 3, 5, and 7 cm. In a second stage the distal end of the graft (Graft.dist.) was coapted to the motor branch of rectus femoris. Cross sections of the normal vastus nerve and the Graft.dist. before and 7 months after the connection to rectus femoris were analyzed histomorphometrically. Before coaptation to the target organ mean fiber number in the Graft.dist. of the 3-cm-long grafts was 3380 and decreased to 2413 in the 7-cm-long grafts. Seven months after coaptation the results showed a statistically significant decrease of fibers in the Graft.dist. of group two and three and a distinct decrease of the fibers in group one. Summarizing, in a two-stage nerve grafting procedure the reinnervation of the muscle target organ leads to a down-regulation of fibers in the distal end of short and long nerve grafts. © 1998 John Wiley & Sons, Inc. Muscle Nerve 21:618–627, 1998.     

Synthesis and Characterization of Manganese-Modified Black TiO2 Nanoparticles and Their Performance Evaluation for the Photodegradation of Phenolic Compounds from Wastewater

The release of phenolic-contaminated treated palm oil mill effluent (TPOME) poses a severe threat to human and environmental health. In this work, manganese-modified black TiO₂ (Mn-B-TiO₂) was produced for the photodegradation of high concentrations of total phenolic compounds from TPOME. A modified glycerol-assisted technique was used to synthesize visible-light-sensitive black TiO₂ nanoparticles (NPs), which were then calcined at 300 °C for 60 min for conversion to anatase crystalline phase. The black TiO₂ was further modified with manganese by utilizing a wet impregnation technique. Visible light absorption, charge carrier separation, and electron–hole pair recombination suppression were all improved when the band structure of TiO₂ was tuned by producing Ti³⁺ defect states. As a result of the enhanced optical and electrical characteristics of black TiO₂ NPs, phenolic compounds were removed from TPOME at a rate of 48.17%, which is 2.6 times higher than P25 (18%). When Mn was added to black TiO₂ NPs, the Ti ion in the TiO₂ lattice was replaced by Mn, causing a large redshift of the optical absorption edges and enhanced photodegradation of phenolic compounds from TPOME. The photodegradation efficiency of phenolic compounds by Mn-B-TiO₂ improved to 60.12% from 48.17% at 0.3 wt% Mn doping concentration. The removal efficiency of phenolic compounds from TPOME diminished when Mn doping exceeded the optimum threshold (0.3 wt%). According to the findings, Mn-modified black TiO₂ NPs are the most effective, as they combine the advantages of both black TiO₂ and Mn doping.     

Discovery and characterization of small molecule inhibitors of the BET family bromodomains

Epigenetic mechanisms of gene regulation have a profound role in normal development and disease processes. An integral part of this mechanism occurs through lysine acetylation of histone tails which are recognized by bromodomains. While the biological and structural characterization of many bromodomain containing proteins has advanced considerably, the therapeutic tractability of this protein family is only now becoming understood. This paper describes the discovery and molecular characterization of potent (nM) small molecule inhibitors that disrupt the function of the BET family of bromodomains (Brd2, Brd3, and Brd4). By using a combination of phenotypic screening, chemoproteomics, and biophysical studies, we have discovered that the protein-protein interactions between bromodomains and acetylated histones can be antagonized by selective small molecules that bind at the acetylated lysine recognition pocket. X-ray crystal structures of compounds bound into bromodomains of Brd2 and Brd4 elucidate the molecular interactions of binding and explain the precisely defined stereochemistry required for activity.