Serpinin in the Skin

The serpinins are relatively novel peptides generated by proteolytic processing of chromogranin A and they are comprised of free serpinin, serpinin-RRG and pGlu-serpinin. In this study, the presence and source of these peptides were studied in the skin. By Western blot analysis, a 40 kDa and a 50 kDa protein containing the sequence of serpinin were detected in the trigeminal ganglion and dorsal root ganglia in rats but none in the skin. RP-HPLC followed by EIA revealed that the three serpinins are present in similar, moderate amounts in rat dorsal root ganglia, whereas in the rat skin, free serpinin represents the predominant molecular form. There were abundant serpinin-positive cells in rat dorsal root ganglia and colocalization with substance P was evident. However, much more widespread distribution of the serpinins was found in dorsal root ganglia when compared with substance P. In the skin, serpinin immunoreactivity was found in sensory nerves and showed colocalization with substance P; as well, some was present in autonomic nerves. Thus, although not exclusively, there is evidence that serpinin is a constituent of the sensory innervation of the skin. The serpinins are biologically highly active and might therefore be of functional significance in the skin.

Postganglionic Sudomotor Assessment in Early Stage of Multiple System Atrophy and Parkinson Disease: A Morpho-functional Study

Background and Objectives:Sudomotor impairment has been recognized as a key feature in differentiating Parkinson disease (PD) and multiple system atrophy-parkinsonian type (MSA-P) with the latter been characterized by diffuse anhidrosis in prospective study including patients in late stage of disease.We aimed to evaluate morphological and functional postganglionic sudomotor involvement in patients with new diagnosis MSA-P and PD to identify possible biomarkers that might be of help in differentiating the two conditions in early stage.Methods:One hundred patients with parkinsonism within 2 years from onset of motor symptoms were included in the study. At time of recruitment, questionnaires to assess non-motor, autonomic and small fiber symptoms were administered and patients underwent post-ganglionic sudomotor function assessment by the dynamic sweat test and punch skin biopsy from distal leg. Skin samples were processed for indirect immunofluorescence with a panel of antibodies including noradrenergic and cholinergic markers. The density of intraepidermal, sudomotor and pilomotor nerve fibers was measured on confocal images using dedicated software. A follow-up visit twelve months after recruitment was performed to confirm the diagnosis.Results:We recruited 57 patients with PD (M/F=36/21; age 63.5±9.4years) and 43 patients with MSA-P (M/F=27/16; age 62.3±9.0 years). Clinical scales and questionnaires showed a more severe clinical picture in MSA-P compared to PD patients. Sweating output and intraepidermal, pilomotor and sudomotor nerve densities, compared to controls, were lower in both groups but with a greater impairment in MSA-P patients. Pilomotor and sudomotor nerve density correlated with sweating function and with non-motor clinical symptoms. A composite sudomotor parameter defined as the arithmetic product of sweat production multiplied by the density of sudomotor fibers, efficiently separated the two populations, the receiver operating characteristics showing an area under the curve of 0.83.Discussion:Dynamic sweat test and the quantification of cutaneous autonomic nerves provided to be a sensitive morpho-functional approach to assess postganglionic component of the sudomotor pathway, revealing a more severe involvement in MSA-P than in PD early in the disease course. This approach can be applied to early differentiate the two conditions.Classification of Evidence:This study provides Class II evidence that post ganglionic sudomotor morpho-functional assessment accurately distinguish PD from MSA-P patients.

Analysis of Heart Rate Asymmetry During Sleep Stages

It is one of the hot spots in recent years to explore changes in the sleep stage by assessing autonomic nervous activity. In recent years, heart rate asymmetry (HRA) is often used to measure the activity of autonomic nerves. However, the relationship between HRA and sleep stage is not clear. We performed Porta’s index (PI), Guzik’s index (GI), slope index (SI) and area index (AI) analyses on RR intervals per 30-s for understanding the HRA during sleep. Two measurement protocols were set: 1) the HRA values were calculated; 2) the degrees of heart rate deviation from symmetry were estimated. Results showed that PI significantly decreased from N1 and N2 to N3 (p<0.01), and it is increased the highest in REM than other stages (p<0.05). The asymmetry of HRA were significantly lower in N3 (PI and AI p’s<0.05; GI and SI p’s<0.01), and it increased in REM (PI p<0.05; GI, SI and AI p’s<0.0001). The results suggested that HRA has the potential to be used in sleep stage monitoring.

A Case Report on Post COVID -19 Vaccine Associated Guillain–Barré Syndrome

Guillain–Barré syndrome (GBS) is an autoimmune demyelinating illness in which a patient’s immune system attacks and cause deterioration of peripheral nervous system leading to progressive paralysis and polyneuropathy. The exact cause of the GBS is unclear but the main mechanism of behindis the demyelination of nerves especially the motor, sensory, and autonomic nerves which can be triggered by any immunologic or infectious agent. The infectious agent elicits the humoral and cellular mediated immune response due to their molecular mimicry in which the antibodies created against the infection matches with the proteins on the nerve. The characteristic features of Guillain–Barré syndrome are ascending flaccid paralysis, paresthesia, impairment of muscle reflexes, respiratory failureetc. The GBS is diagnosed via nerve conduction studies, lumbar puncture (Cerebrospinal fluid analysis), electromyography, Brighton criteria. Treatments like intravenous immunoglobulin therapy, plasma exchange can ease the symptoms and reduce the duration of the illness. This case report focusing on a 43-year-old female patient admitted seeking ventilatory support for respiratory distress caused by Guillain–Barré Syndrome in a tertiary hospital. Patient had developed limb weakness with ascending paralysis along with facial weakness within a couple of weeks after receiving the COVID -19 vaccination (COVISHIELD)one month back. Patient underwent nerve conduction study and routine monitoring of vital parameters. After conservative management with physiotherapy, ventilation, intravenous immunoglobulins and prophylaxis for pain and DVT patient gradually started improving the muscle power and was discharged to continue the rehabilitation care at home.

Similarity Changes Analysis for Heart Rate Fluctuation Regularity as a New Screening Method for Congestive Heart Failure

Congestive heart failure (CHF) is a chronic cardiovascular condition associated with dysfunction of the autonomic nervous system (ANS). Heart rate variability (HRV) has been widely used to assess ANS. This paper proposes a new HRV analysis method, which uses information-based similarity (IBS) transformation and fuzzy approximate entropy (fApEn) algorithm to obtain the fApEn_IBS index, which is used to observe the complexity of autonomic fluctuations in CHF within 24 h. We used 98 ECG records (54 health records and 44 CHF records) from the PhysioNet database. The fApEn_IBS index was statistically significant between the control and CHF groups (p < 0.001). Compared with the classical indices low-to-high frequency power ratio (LF/HF) and IBS, the fApEn_IBS index further utilizes the changes in the rhythm of heart rate (HR) fluctuations between RR intervals to fully extract relevant information between adjacent time intervals and significantly improves the performance of CHF screening. The CHF classification accuracy of fApEn_IBS was 84.69%, higher than LF/HF (77.55%) and IBS (83.67%). Moreover, the combination of IBS, fApEn_IBS, and LF/HF reached the highest CHF screening accuracy (98.98%) with the random forest (RF) classifier, indicating that the IBS and LF/HF had good complementarity. Therefore, fApEn_IBS effusively reflects the complexity of autonomic nerves in CHF and is a valuable CHF assessment tool.

The first experience of ultrasound-guided percutaneous microwave ablation for extracranial schwannoma of the cervical vagus nerve in carotid space and treatment response evaluation with contrast-enhanced imaging

Schwannoma is a benign tumor that originates from Schwann cells in the nerve sheathing of cranial, other peripheral, or autonomic nerves. Patients often present with painless mass as the chief complaint. The main symptoms of this tumor are related to its size and specific nerve origin. At present, the pretreatment diagnosis is mainly made by ultrasound, CT, MR, or biopsy, and the main treatment is surgical resection. We reported a new treatment method for cervical schwannoma in a 65-year-old woman with a history of non-small cell lung cancer (NSCLC). When the patient’s neck mass was initially found with hoarseness and severe cough, it was considered as cervical lymph node metastasis of lung cancer due to her medical history. And she was diagnosed with schwannoma by core-needle biopsy after chemotherapy failed and the tumor shrank after the radiotherapy with no improvement of the clinical symptoms. After considering the physical condition, the patients were treated in our department for minimal invasiveness treatment. The patient was definitively diagnosed with cervical vagus schwannoma and was treated with ultrasound-guided microwave ablation of schwannoma under general anesthesia with systematic evaluation and improved preoperative examination. Her condition was stable, and the symptoms of severe cough disappeared after anesthesia resuscitation and the ablation. The tumor continued to shrink after the operation with no recurrence of cough symptoms. Ultrasound-guided percutaneous microwave ablation (MWA) for cervical vagus schwannomas might be a minimally invasive, effective, and relatively safe alternative to conventional treatment for those patients with severe symptoms.

Nerve-Sparing Radical Hysterectomy Using the Okabayashi–Kobayashi Method

Radical hysterectomy (RH) is a standard treatment for early-stage cervical cancer. This surgery extirpates the uterus along with the paracervical tissues, vagina, and the paracolpium to achieve local control. Pelvic lymphadenectomy is a critical component of RH performed for regional control. A clear understanding of pelvic anatomy is critical to safely performing a RH and achieving optimal oncological and functional outcomes. The various surgical steps can damage the pelvic autonomic nerves, and a systematic nerve-sparing technique is used for the preservation of autonomic nerves. There is an intricate vascular network in the lateral paracervix (cardinal ligament) and the pelvic sidewall. We need to comprehend the three-dimensional structure of the vascular and nerve anatomy in the pelvis to perform RH effectively and safely. We can create six spaces around the uterine cervix, including the paravesical spaces, pararectal spaces, a vesicovaginal space, and a rectovaginal space to reveal the target of extirpation. It is critical to find the proper tissue plane separated by the layers of membranous connective tissue (fascia), in order to minimize intraoperative bleeding.

The role, carrier and mission of neural crest cells in the skin

The neuro crest arising from the ectoderm is a transient structure and disappears as the neurocrest cells leave these places to invade the whole embryo. The epidermis develops from the ectoderm in the fourth embryonal weeks. The embryos consist of cranial-,vagal-, truncal and sacral segments and the neuro crest cells migrate from these places to form various structures, including the peripheral nerve system, the craniofacial bones and cartilages, etc. The neuro crest cells degrade the basal membrane of neural tube and thereafter migrate through the extracellular matrix in ventromedial and dorsolateral direction. Neural crest cells use various cell adhesion molecules and diferent proteaes. The invasive capacity of these cells is infuenced by aquaporin-1 , too. . The sensory nerves developig from the neuro- crest cells can be found in the epidermis and its appendicular organ, the dermal autonomic nerves in the dermis. The epidermal melanocytes develop partly from the neural crest cells, partly from the Schwann cells of the sensory nerves. The cutaneous nerves produce and secrete neuropeptides thus contributing to the development of the skin into a neuroimmuno-endocrin organ.

The Effect of Wet Cupping on Baroreceptor Sensitivity in Hypertensive Patients in Sidenreng Rappang Regency, South Sulawesi

Wet cupping therapy removes toxins thereby increasing blood flow and stimulating baroreceptors sensitivity which provides a stimulus to the autonomic nerves. This stimulus reduces the sympathetic nerves’ work and inhibits the vasomotor center, leading to vasodilation, therefore decreasing blood pressure and pulse frequency. This research aims to determine the effect of wet cupping therapy on baroreceptors sensitivity with blood pressure and pulse frequency indicators. It was conducted in Sidenreng Rappang Regency, South Sulawesi, eastern Indonesia from February to May 2021. Randomized Controlled Trial (RCT) method was used including two groups of 31 respondents each. The intervention group used wet cupping therapy to regulate anti-hypertensive drugs and the control group used anti-hypertensive drugs with blood pressure and pulse frequency measurements until 6 weeks after the therapy. Wet cupping affects baroreceptor sensitivity by reducing the indicators. The result showed a significant difference in blood pressure measurement (systolic; diastolic) before and after the 2-week follow-up period (P = 0.000; P = 0.001), and between 2 and 4 weeks (P = 0.000; P = 0.000), but between 4 and 6 weeks there was no significant difference in the intervention group (P = 0.248; P = 0.583). There was a significant difference in pulse frequency at 2 and 4 weeks after the intervention (P = 0.016). In conclusion, wet cupping therapy effectively increases baroreceptor sensitivity by reducing blood pressure and pulse frequency indicators in hypertensive patients up to 4 weeks limit after the therapy, without any serious side effects experienced by respondents.

Three-dimensional anatomy of the Denonvilliers’ fascia after micro-CT reconstruction

An understanding of the anatomy of the Denonvilliers’ fascia is essential for successful surgical outcomes for patients with rectal cancer in the mid- to lower regions, especially near the seminal vesicles and prostate in males. Whether the correct surgical plane during a total mesorectal excision should be anterior or posterior to the Denonvilliers’ fascia is currently under debate. This study aimed to investigate the Denonvilliers’ fascia using micro-computed tomography (micro-CT) to acquire three-dimensional images nondestructively for assessments of the relationship between the Denonvilliers’ fascia, the mesorectal fascia, and neurovascular bundles to elucidate the correct anterior total mesorectal excision plane. Eight specimens were obtained bilaterally from four fresh human cadavers. Four specimens were stained with phosphotungstic acid to visualize the soft tissue, and micro-CT images were obtained; the other four specimens were stained with Masson’s trichrome to visualize connective tissue. Micro-CT images corroborate that the Denonvilliers’ fascia consists of a multilayered structure that separates the rectum from the seminal vesicles and the prostate. Specimens stained with Masson’s trichrome showed that the urogenital neurovascular bundle located at the posterolateral corner of the prostate is separated from the mesorectum by the Denonvilliers’ fascia. For the preservation of autonomic nerves necessary for urogenital function and optimal oncologic outcomes in patients with rectal cancer, a successful mesorectal excision requires a dissection plane posterior to the Denonvilliers’ fascia.