Early phase of pupil dilation is mediated by the peripheral parasympathetic pathway

Pupil diameter fluctuates in association with changes in brain states induced by the neuromodulator systems. However, it remains unclear how the neuromodulator systems control the activity of the iris sphincter (constrictor) and dilator muscles to change the pupil size. The present study compared temporal patterns of pupil dilation during movement when each muscle was pharmacologically manipulated in the human eye. When the iris sphincter muscle was blocked with tropicamide, the latency of pupil dilation was delayed and the magnitude of pupil dilation was reduced during movement. In contrast, when the iris dilator muscle was continuously stimulated with phenylephrine, the latency and magnitude of rapid pupil dilation did not differ from the untreated control eye, but sustained pupil dilation was reduced until the end of movement. These results suggest that the iris sphincter muscle, which is under the control of the parasympathetic pathway, is quickly modulated by the neuromodulator system and plays a major role in rapid pupil dilation. However, the iris dilator muscle receives signals from the neuromodulator system with a slow latency and is involved in maintaining sustained pupil dilation.

Autoantigen characterization in the lower esophageal sphincter muscle of patients with achalasia.

OBJECTIVE: To characterize in sera anti-myenteric autoantibody profiles and in tissues MMP-9 proteoforms towards the identification of possible autoantigenic proteins in the muscle of the lower esophageal sphincter (LES) of achalasia patients. METHODS: Biopsies of the LES muscle from 36 achalasia patients, 6 esophagogastric junction outflow obstruction (EGJOO) patients, and 16 transplant donors (TD) were compared in a blind cross-sectional study. Histological characteristics such as inflammation, fibrosis, presence of ganglion cells, cells of Cajal, GAD65, PNMA2, S100, P substance, and MMP-9 proteforms in tissue were assessed by H&E and Picro-Sirius Red stainings, and immunohistochemistry analysis. Antineuronal antibodies (amphiphysin, CV2, and PNMA2 (Ma2/Ta)), onconeural antigens (Ri, Yo, and Hu), recoverin, SOX-1, titin, zic4, GAD65, and Tr (DNER) were evaluated by immunoblot/line assay. RESULTS: Tissue of achalasia patients had heterogeneous inflammatory infiltrates with fibrosis and contrasting higher levels of activated MMP-9 compared with EGJOO and TD. Moreover, lower ganglion cell percentages and cell of Cajal percentages were determined in esophageal tissues of achalasia patients vs. TD. In addition, tissue of achalasia patients had higher GAD65 and PNMA2 protein expression vs. EGJOO. Unexpectedly, these proteins were absent in TD tissue. S100 and P substance had similar expression levels in tissues of achalasia patients vs.TD and EGJOO. Most of the achalasia sera had anti-GAD65 (83%) and anti-PNMA2 (90%) autoantibodies vs. EGJOO (17% and 33%, respectively) and healthy volunteers (10% and 0%, respectively). CONCLUSION: Tissue-specific ectopic expression of GAD65 and PNMA/Ta2 and active MMP-9, associated with the presence of specific autoantibodies directed against these proteins, might participate in the pathophysiology of achalasia triggering and/or perpetuating autoimmune disease.

Combination of PD98059 and TGF-β1 Efficiently Differentiates Human Urine-Derived Stem Cells into Smooth Muscle Cells

Pluripotent adult stem cells have potential applications in cell therapy and tissue engineering. Urine-derived stem cells (UDSCs) differentiate into various cell types. Here, we attempted to differentiate human UDSCs (hUDSCs) into smooth muscle cells (SMCs) using transforming growth factor-beta 1 (TGF-β1) and/or PD98059, an extracellular signal-regulated kinase (ERK) inhibitor. Both quantitative polymerase chain reaction (qPCR) and Western blot analysis showed that the expression of messenger ribonucleic acid (mRNA) and proteins for alpha-smooth muscle actin (α-SMA), calponin (CNN1), and smooth muscle myosin heavy chain (SM-MHC), which are specific markers for SMCs, increased on day 9 after differentiation and again on day 14. The differentiated cells from human UDSCs (hUDSCs) with a combination of TGF-β1 and PD98059 showed the highest expression of SMC marker proteins. Immunocytochemical staining performed to assess the molecular expression revealed CNN and α-SMA colocalizing in the cytoplasm. The cells that differentiated from hUDSCs with a combination of TGF-β1 and PD98059 showed the strongest expression for CNN1, α-SMA, and SM-MHC. Functional testing of the differentiated cells revealed a stronger contractile capacity for the cells differentiated with a combination of PD98059 and TGF-β1 than those differentiated with a single factor. These results suggest the combination of PD98059 and TGF-β1 to be a more effective differentiation method and that differentiated SMCs could be used for restoring the functions of the sphincter muscle or bladder.

Management of Bhagandar (Fistula in ano) by Ksharasutra – A Review

Bhagandara is a single or multiple opening around guda Pradesh associated with different types of discharge along with pain. Acharya sushruta has described bhagandara on its consequences under astamahagada. The disorder has reached a height due to an unhealthy lifestyle. It can be correlated with fistula in ano. Fistula in ano is an abnormal hollow tract or cavity lined with granulation tissue. It is a nasty condition for the patient and often creates issue which leads to unease. It affects their daily lifestyle. For the treatment number of the surgical method are available.In Ayurveda, Acharya Sushruta has described various types of treatment like Chedana karma, Ksharasutra therapy. In modern science fistulectomy, fistulotomy, seton, and so on. But due to reoccurrence, damage of the anal ring, incontinence, and complication, Ksharasutra stands as a major para surgical procedure to cure bhaganadara. Ksharasutra is a unique medicated thread that helps in cutting as well as drainage of the fistulous tract. It works as cutting and healing of fistulous tract simultaneously. Hence the possibility of damage to the anorectal sphincter muscle is less and chances of incontinence are null. It is safe minimal, cheap, and easy to use. It works effectively on various stages.

Perianal ultrasound (PAUS): visualization of sphincter muscles and comparison with digital-rectal examination (DRE) in females

Background The aim of this study was to determine the reproducibility and tolerance of perianal ultrasound (PAUS) and detect differences in sphincter muscles between various measuring positions and different maneuvers. PAUS was compared to digital-rectal examination (DRE) to see if sphincter contraction is visible and gradable in ultrasound volumes. Methods Fifty women underwent a medical history, DRU and PAUS by two uro-gynecologists in a prospective trial. PAUS volumes were measured via different parameters in different maneuvers. Examiners’ DRE impressions of sphincter tone were scaled with the DRESS-score. All patients completed a questionnaire. Results Thirty-five patients with complete PAUS and DRE were included in the study. Fifteen patients were excluded due to poor ultrasound volume quality or sphincter defects. Comparison of sphincter muscle thickness at different positions in PAUS showed significant differences between 6 and 12 o’clock positions (12 > 6 o’clock) and diameters (horizontal > vertical). No difference was found between the examiners. In comparison of rest and contraction only the vertical diameter changed. There was a negative but not significant correlation between PAUS measurements and DRESS-scores. Twenty-six patients completed the questionnaire that revealed women preferred PAUS over DRE. Conclusion PAUS is a reproducible and good tool to visualize the anal canal. It is comfortable for patients and easily handled by examiners. Sphincter muscle contraction is iso-volumetric. Vertical diameter changes during contraction leading the anal canal change its shape to oval due to external influence. PAUS is the ideal additional tool to visualize relevant structures that are palpable on DRE.

Novel Techniques to Improve Precise Cell Injection

We noted recently that the injection of cells with a needle through a cystoscope in the urethral sphincter muscle of pigs failed to deposit them nearby or at the intended target position in about 50% of all animals investigated (n > 100). Increasing the chance for precise cell injection by shotgun approaches employing several circumferential injections into the sphincter muscle bears the risk of tissue injury. In this study, we developed and tested a novel needle-free technique to precisely inject cells in the urethral sphincter tissue, or other tissues, using a water-jet system. This system was designed to fit in the working channels of endoscopes and cystoscopes, allowing a wide range of minimally invasive applications. We analyze key features, including the physical parameters of the injector design, pressure ranges applicable for tissue penetration and cell injections and biochemical parameters, such as different compositions of injection media. Our results present settings that enable the high viability of cells post-injection. Lastly, the method is suitable to inject cells in the superficial tissue layer and in deeper layers, required when the submucosa or the sphincter muscle of the urethra is targeted.

Orbicularis Oculi Muscle Size and Function: Exploring the Influence of Aging and Exercise Training

The orbicularis oculi muscle is the sphincter muscle of the eyelids that blinks and closes the eyes. In this review, our aim was threefold: (1) to introduce the performance characteristics of blinking activity in young and older adults, (2) to discuss the influence of aging on the orbicularis oculi muscle in healthy adults, and (3) to provide information about the effect of facial exercise training on the orbicularis oculi muscle. To achieve the purpose of this review, a search using two electronic databases (PubMed and Scopus) and a search engine (Google Scholar) was conducted. The amplitude and peak velocity of spontaneously blinking behavior, which is an index of muscle function of the orbicularis oculi, appear to be affected by aging. The muscle thickness of the orbicularis oculi tends to be low in older adults, but there are issues that need to be examined further, such as differences in sex and measurement positions. There was no study on the effect of exercise training; however, the results of a highly trained man indicate that the orbicularis oculi muscles might elicit muscle hypertrophy through non-traditional resistance exercise.

Delivery of the 5-HT2A Receptor Agonist, DOI, Enhances Activity of the Sphincter Muscle during the Micturition Reflex in Rats after Spinal Cord Injury

Traumatic spinal cord injury (SCI) interrupts spinobulbospinal micturition reflex pathways and results in urinary dysfunction. Over time, an involuntary bladder reflex is established due to the reorganization of spinal circuitry. Previous studies show that manipulation of serotonin 2A (5-HT2A) receptors affects recovered bladder function, but it remains unclear if this receptor regulates the activity of the external urethral sphincter (EUS) following SCI. To elucidate how central and peripheral serotonergic machinery acts on the lower urinary tract (LUT) system, we employed bladder cystometry and EUS electromyography recordings combined with intravenous or intrathecal pharmacological interventions of 5-HT2A receptors in female SCI rats. Three to four weeks after a T10 spinal transection, systemic and central blockage of 5-HT2A receptors with MDL only slightly influenced the micturition reflex. However, delivery of the 5-HT2A receptor agonist, DOI, increased EUS tonic activity and elicited bursting during voiding. Additionally, subcutaneous administration of DOI verified the enhancement of continence and voiding capability during spontaneous micturition in metabolic cage assays. Although spinal 5HT2A receptors may not be actively involved in the recovered micturition reflex, stimulating this receptor subtype enhances EUS function and the synergistic activity between the detrusor and sphincter to improve the micturition reflex in rats with SCI.