Proteomic analysis of Red Sea Conus taeniatus venom reveals potential biological applications

Diverse and unique bioactive neurotoxins known as conopeptides or conotoxins are produced by venomous marine cone snails. Currently, these small and stable molecules are of great importance as research tools and platforms for discovering new drugs and therapeutics. Therefore, the characterization of Conus venom is of great significance, especially for poorly studied species. Methods: In this study, we used bioanalytical techniques to determine the venom profile and emphasize the functional composition of conopeptides in Conus taeniatus, a neglected worm-hunting cone snail. Results: The proteomic analysis revealed that 84.0% of the venom proteins were between 500 and 4,000 Da, and 16.0% were > 4,000 Da. In C. taeniatus venom, 234 peptide fragments were identified and classified as conotoxin precursors or non-conotoxin proteins. In this process, 153 conotoxin precursors were identified and matched to 23 conotoxin precursors and hormone superfamilies. Notably, the four conotoxin superfamilies T (22.87%), O1 (17.65%), M (13.1%) and O2 (9.8%) were the most abundant peptides in C. taeniatus venom, accounting for 63.40% of the total conotoxin diversity. On the other hand, 48 non-conotoxin proteins were identified in the venom of C. taeniatus. Moreover, several possibly biologically active peptide matches were identified, and putative applications of the peptides were assigned. Conclusion: Our study showed that the composition of the C. taeniatus-derived proteome is comparable to that of other Conus species and contains an effective mix of toxins, ionic channel inhibitors and antimicrobials. Additionally, it provides a guidepost for identifying novel conopeptides from the venom of C. taeniatus and discovering conopeptides of potential pharmaceutical importance.(AU)

Isolation and structural identification of a new T1-conotoxin with unique disulfide connectivities derived from Conus bandanus

Conopeptides are neuropharmacological peptides derived from the venomous salivary glands of cone snails. Among 29 superfamilies based on conserved signal sequences, T-superfamily conotoxins, which belong to the smallest group, include four different frameworks that contain four cysteines denominated I, V, X and XVI. In this work, the primary structure and the cysteine connectivity of novel conotoxin of Conus bandanus were determined by tandem mass spectrometry using collision-induced dissociation. Methods: The venom glands of C. bandanus snails were dissected, pooled, and extracted with 0.1% trifluoroacetic acid in three steps and lyophilized. The venom was fractionated and purified in an HPLC system with an analytical reversed-phase C18 column. The primary peptide structure was analyzed by MALDI TOF MS/MS using collision-induced dissociation and confirmed by Edman's degradation. The peptide's cysteine connectivity was determined by rapid partial reduction-alkylation technique. Results: The novel conotoxin, NGC1C2(I/L)VREC3C4, was firstly derived from de novo sequencing by MS/MS. The presence of isoleucine residues in this conotoxin was confirmed by the Edman degradation method. The conotoxin, denominated Bn5a, belongs to the T1-subfamily of conotoxins. However, the disulfide bonds (C1-C4/C2-C3) of Bn5a were not the same as found in other T1-subfamily conopeptides but shared common connectivities with T2-subfamily conotoxins. The T1-conotoxin of C. bandanus proved the complexity of the disulfide bond pattern of conopeptides. The homological analysis revealed that the novel conotoxin could serve as a valuable probe compound for the human-nervous-system norepinephrine transporter. Conclusion: We identified the first T1-conotoxin, denominated Bn5a, isolated from C. bandanus venom. However, Bn5a conotoxin exhibited unique C1-C4/C2-C3 disulfide connectivity, unlike other T1-conotoxins (C1-C3/C2-C4). The structural and homological analyses herein have evidenced novel conotoxin Bn5a that may require further investigation.(AU)

Prokaryotic expression and hypoglycemic activity determination of insulin G1 from Conus geographus / 生物工程学报

Rapid reduction of postprandial blood glucose is very beneficial to diabetics. In order to shorten the onset time of recombinant insulin, the cone snail insulin G1 (cI G1) of Conus geographus was studied. First, the nucleotide sequence of recombinant cone snail proinsulin G1 (cPI G1) was designed and synthesized according to the genes of human proinsulin (hPI) and cPI G1. The codon was optimized according to Escherichia coli (E. coli) codon usage frequency. Then, the plasmid pET22b(+)-cPI G1 was constructed and the recombinant cPI G1 was expressed in E. coli BL21(DE3) host strain. The recombinant cPI G1 was then purified and cleaved specially by trypsin to generate the recombinant cI G1, and its potency is 25.9 IU/mg. Fasting blood glucose test (FBGT) and oral glucose tolerance test (OGTT) suggested that the recombinant cI G1 could rapidly reduce blood glucose in normal and streptozotocin (STZ)-induced diabetic mice, but only for a short duration. This study provides a technical reference for the development of recombinant fast-acting insulin.

Magnetic Resonance Imaging Observations of the Conus Medullaris in a Korean Population

STUDY DESIGN: Retrospective study (level of evidence: level 3). PURPOSE: To study the anatomy of the conus medullaris in Koreans. OVERVIEW OF LITERATURE: The anatomical position of the conus medullaris is well-documented in anatomy textbooks; however, the shape of the conus in the canal rarely described. Furthermore, to our knowledge, no study in Korea has not yet assessed the shape of the conus as well as its position in the canal via cadavaric dissection and/or magnetic resonance imaging (MRI). METHODS: MRI findings of 189 Korean patients aged 2–94 years (93 men and 94 women) were assessed. No subjects from other ethnicities were included. The method proposed by Arai and colleagues was used to assess the termination point and shape of the conus in the canal. The position of the intervertebral disc trisection of the vertebral body closest to the tip of the conus was recorded at the canal level. RESULTS: The tip of the conus medullaris was positioned from the upper T12 body to the L2–L3 disc, mostly in L1 bodies (52.4%), followed by the L2 bodies (22.5%), the L1–L2 disc, and the L2–L3 disc (1.1%). The shape of the conus was classified as type A in 74 (39.6%), type B in 58 (31%), and type C in 55 patients (29.4%). The conus did not terminate at the L3 body in any patient. In the first decade ones (five children) conus positioned rather lowly from L1 bodies to L2–L3 disc, and no type A conus shape, and mostly type B (80%). CONCLUSIONS: The conus medullaris was positioned mostly in the lower one-third of L1 and it in the first decades terminated lowly. No type A in the first decade one, and type B was mostly frequently formed which was followed by type C.

Unusual Communication between the Pulmonary Artery and Vieussens’ Arterial Ring Causing Infective Endocarditis / 대한흉부외과학회지

Coronary artery fistula is an abnormal communication between the coronary artery and the cardiac chambers. In particular, an abnormal connection between the conus branch of the right coronary artery and the proximal left anterior descending coronary artery is defined as Vieussens’ arterial ring. Coronary artery fistulas are usually asymptomatic, but some can cause complications such as infective endocarditis. Here, we report a case of Vieussens’ arterial ring causing infective endocarditis with severe mitral regurgitation.

Conus Medullaris Levels on Ultrasonography in Term Newborns : Normal Levels and Dermatological Findings

OBJECTIVE: Ultrasonography (US) is the most non-invasive, safe, and, especially in the period of infancy, best method for visualizing and examining the spinal cord. Furthermore, US is the primary work-up for development of the spinal canal, and for follow-up on issues relating to subcutaneous tissues, bone development, and the spinal cord. Conus medullaris terminates at the second lumbar vertebra, according to a consensus in the literature.METHODS: Healthy children under the age of 6 months who were admitted to the radiology clinic for routine USG follow-ups between the dates of March 2012 to December 2014 were included in this study.RESULTS: Our study includes data from 1125 lumbosacral ultrasounds. The terminal point of the conus level of the attended infants, superior, middle part, inferior of the vertebrae L1, L2, and L3. Furthermore, the termination of the discal distance ratio did not differ significantly between genders.CONCLUSION: Therefore, according to our results, gender is not an influencing factor in the termination of the spinal cord. Based on the study we performed, as well as the previous literature, in infants without a recognized spinal pathology, the spinal cord is detected below the vertebra L3.

Conus Medullaris Levels on Ultrasonography in Term Newborns : Normal Levels and Dermatological Findings

OBJECTIVE: Ultrasonography (US) is the most non-invasive, safe, and, especially in the period of infancy, best method for visualizing and examining the spinal cord. Furthermore, US is the primary work-up for development of the spinal canal, and for follow-up on issues relating to subcutaneous tissues, bone development, and the spinal cord. Conus medullaris terminates at the second lumbar vertebra, according to a consensus in the literature. METHODS: Healthy children under the age of 6 months who were admitted to the radiology clinic for routine USG follow-ups between the dates of March 2012 to December 2014 were included in this study. RESULTS: Our study includes data from 1125 lumbosacral ultrasounds. The terminal point of the conus level of the attended infants, superior, middle part, inferior of the vertebrae L1, L2, and L3. Furthermore, the termination of the discal distance ratio did not differ significantly between genders. CONCLUSION: Therefore, according to our results, gender is not an influencing factor in the termination of the spinal cord. Based on the study we performed, as well as the previous literature, in infants without a recognized spinal pathology, the spinal cord is detected below the vertebra L3.

Conus Medullaris Syndrome Due to Posterior Spinal Artery Infarction

A 77-year-old female with a history of osteoarthritis visited our clinic complaining of lower back pain, paresthesia in both legs, and voiding difficulty. Her pain and temperature sensations were diminished below the L1 dermatome, and proprioception was decreased in both feet. The findings of a routine laboratory workup, echocardiogram, and cerebrospinal fluid studies were normal. Spine magnetic resonance imaging revealed high T2-weighted signal intensities and diffusion restriction in the posterior conus medullaris. The patient was diagnosed and treated for posterior spinal artery infarction.

Trifurcation of right coronary artery and its huge right ventricular branch: can it be hazardous? / 대한해부학회지

The objective of this case report is to alert the cardiologists and radiologists about the possibility of an extremely rare trifurcation of the right coronary artery. During dissection classes, an early trifurcation of the right coronary artery (RCA) was observed in an adult male cadaver aged approximately 65 years. The RCA had a normal origin from the anterior aortic sinus. After a course of just 2 mm, it trifurcated into a conus artery, a huge right ventricular branch and then a main continuation of the RCA. The conus artery entered the myocardium of the conus after a short course. The huge ventricular branch had a downward and left course almost till the apex of the heart. Right marginal artery was absent. No other vascular variations of heart were observed apart from this. Knowledge of this trifurcation could be useful in coronary angioplasty and bypass procedures.

Comparison of retention forces with various fabrication methods and materials in double crowns

PURPOSE: The purpose of this study was to analyze the retention force changes and wear behaviours of double-crown systems over long-term use. MATERIALS AND METHODS: Ten groups, each consisting of six samples, were evaluated. Specifically, casting gold alloy primary crown - casting gold alloy secondary crown (AA), laser sintering primary crown - laser sintering secondary crown (LL), casting Cr alloy primary crown - casting Cr alloy secondary crown, (CC) zirconia primary crown - electroformed secondary crown (ZA), and CAD/CAM titanium alloy primary crown - CAD/CAM titanium alloy secondary crown (TT) groups were evaluated at cone angles of 4° and 6°. The samples were subjected to 5,000 insertion-separation cycles in artificial saliva, and the retention forces were measured every 500 cycles. The wear levels were analyzed via SEM at the beginning and end of the 5,000 cycles. RESULTS: In all samples, the retention forces increased when the conus angle decreased. The highest initial and final retention force values were found in the LL-4° group (32.89 N-32.65 N), and the lowest retention force values were found in the ZA6° group (5.41 N-6.27 N). The ZA groups' samples showed the least change in the retention force, and no wear was observed. In the other groups, wear was observed mostly in the primary crowns. CONCLUSION: More predictable, clinically relevant, and less excursive retention forces can be observed in the ZA groups. The retention force values of the LL groups were statically similar to those of the other groups, except the ZA groups.

The Tip Level of the Conus Medullaris by Magnetic Resonance Imaging and Cadaver Studies in Korean Adults / 체질인류학회지

The spinal cord is part of the central nervous system, and its caudal end is named as the conus medullaris. Many researchers have reported the tip level of the conus medullaris by magnetic resonance imaging studies; others by cadaver dissection. The tip level of magnetic resonance imaging studies seemed to be higher than that of cadaver studies. We evaluated the tip level the conus medullaris with magnetic resonance imaging and cadaver dissection in Korean adult population. MR data were scanned with T1-weighted, mid-sagittal magnetic resonance imaging of 248 living persons (mean age, 42.3±16.0 years; range, 12-85 years) and cadaver data were collected by dissections of 118 cadavers (mean age, 56.0±14.9 years; range, 16-94 years). The mean level of conus tip was found to be at the middle third of 1st lumbar vertebra (range, lower third T12 - lower third L2) from magnetic resonance imaging study and the upper third of 2nd lumbar vertebra (range, lower third T12 - lower third L3) from cadaver dissection study. The tip level of conus medullaris from magnetic resonance imaging study was higher than that from cadaver dissection study (p<0.05).

Morphometric Analysis of Distances between Sacral Hiatus and Conus Medullaris Using Magnetic Resonance Image in Korean Adult / 체질인류학회지

The purpose of this study was to provide basic biometric data on Korean adults through magnetic resonance imaging (MRI)-based measurements of the distances between the apex of sacral hiatus (SH) and the termination of dural sac (DS), and between SH and conus medullaris (CM) because they are critical to the performance of epidural neuroplasty. A total of 200 patients (88 males and 112 females) with back pain, who had no spine fracture, significant spinal deformity, and spondyloisthesis were selected for this study. The subjects were of mean age 54.3 (20~84) years and mean height 161.3 cm (135~187). T2-weighted MRI images were used for correlation analysis to evaluate the relationships between the distances, and variables such as sex and height. In all patients, the mean distance between SH and DS was 62.8±9.4 mm and the mean distance between SH and CM was 232.2±21.8 mm. The minimum distance and the maximum distance between SH and DS were 34.8 mm and 93.9 mm respectively, and the minimum distance and the maximum distance between SH and CM were 155.0 mm and 284.0 mm respectively. In female patients, both the distances between the SH and DS, and between SH and CM were shorter when compared to those of the male patients (p<0.05). Both the distances between SH and DS and between SH and CM showed a significant correlation with height (p<0.01). The results of this study will provide a useful biometric data on the distances between SH and DS and between SH and CM in Korean in ensuring clinical safety and in the development of more effective catheterization techniques for epidural neuroplasty in Korean.

Ruptured Dermoid Cyst in the Conus Medullaris Detected by Susceptibility Weighted Imaging of the Brain

No abstract available.

Nerve injury in an undiagnosed adult tethered cord syndrome patients following spinal anesthesia: A case report

Spinal anesthesia is a safe and widely used procedure. Spinal cord injury is a rare but serious complication from spinal anesthesia occurs, unexpectedly. Risks of direct neural injury from spinal anesthesia increase in tethered cord syndrome that the spinal cord is tethered by the inelastic structure and is, also, extended to the lower lumbar vertebra. A 52-years-old female patient undergoing anti-incontinence surgery developed neurologic symptoms following spinal anesthesia. The low-lying conus (L5 body level) and tethered cord were found during the assessment of neurological symptoms.

Fully Endoscopic Interlaminar Detethering of Spinal Cord in Tethered Cord Syndrome: A Case Report and Technical Description

A 19-year-old man presented with long lasting significant back and bilateral leg pain, and hypoesthesia on the lateral side of both his thighs for which he had undergone several courses of medication and bouts of physical therapy treatment. His urodynamic parameters were normal and lumbar magnetic resonance imaging (MRI) revealed a low-lying conus at the L2-3 level with a thickened fatty filum, and he was diagnosed as having tethered cord syndrome (TCS). The patient underwent a fully endoscopic detethering through an interlaminar approach with intraoperative neurophysiological monitoring. The thickened filum terminale was located and then the filum was coagulated and cut. The patient showed a significant improvement in his preoperative symptoms, and reported no problems at 2-year follow-up. Detethering of the spinal cord in tethered cord syndrome using a fully endoscopic interlaminar approach provides the advantages of minimal damage to tissues, less postoperative discomfort, early postoperative recovery, and a shorter hospitalization.

Paraplegia Following Intercostal Nerve Neurolysis with Alcohol and Thoracic Epidural Injection in Lung Cancer Patient

The goal of cancer treatment is generally pain reduction and function recovery. However, drug therapy does not treat pain adequately in approximately 43% of patients, and the latter may have to undergo a nerve block or neurolysis. In the case reported here, a 42-year-old female patient with lung cancer (adenocarcinoma) developed paraplegia after receiving T8-10 and 11th intercostal nerve neurolysis and T9-10 interlaminar epidural steroid injections. An MRI results revealed extensive swelling of the spinal cord between the T4 spinal cord and conus medullaris, and T5, 7-11, and L1 bone metastasis. Although steroid therapy was administered, the paraplegia did not improve.

Can MRI Findings Help to Predict Neurological Recovery in Paraplegics With Thoracolumbar Fracture?

OBJECTIVE: To evaluate the usefulness of various magnetic resonance imaging (MRI) findings in the prognosis of neurological recovery in paraplegics with thoracolumbar fracture using association analysis with clinical outcomes and electrodiagnostic features. METHODS: This retrospective study involved 30 patients treated for paraplegia following thoracolumbar fracture. On axial and sagittal T2-weighted MRI scans, nerve root sedimentation sign, root aggregation sign, and signal intensity changes in the conus medullaris were independently assessed by two raters. A positive sedimentation sign was defined as the absence of nerve root sedimentation. The root aggregation sign was defined as the presence of root aggregation in at least one axial MRI scan. Clinical outcomes including the American Spinal Injury Association impairment scale, ambulatory capacity, and electrodiagnostic features were used for association analysis. RESULTS: Inter-rater reliability of the nerve root sedimentation sign and the root aggregation sign were kappa=0.67 (p=0.001) and kappa=0.78 (p<0.001), respectively. A positive sedimentation sign was significantly associated with recovery of ambulatory capacity after a rehabilitation program (chi2=4.854, p=0.028). The presence of the root aggregation sign was associated with reduced compound muscle action potential amplitude of common peroneal and tibial nerves in nerve conduction studies (chi2=5.026, p=0.025). CONCLUSION: A positive sedimentation sign was significantly associated with recovery of ambulatory capacity and not indicative of persistent paralysis. The root aggregation sign suggested the existence of significant cauda equina injuries.

Neurological Outcome after Surgical Treatment of Intramedullary Spinal Cord Tumors

OBJECTIVE: Recently, surgical outcomes of patients with intramedullary spinal cord tumors (IMSCT) have been improved due to advances of medicine. The purposes of our study were to evaluate the recent neurological outcomes after surgical treatment of IMSCTs. METHODS: We retrospectively reviewed 69 patients who underwent surgical treatment for IMSCT in our hospital between 1998 and 2013. Patient's age, sex, histological origin and grade, tumor location, tumor extension, preoperative neurological state, initial presenting symptom, and extend of tumor resection were analyzed to evaluate predictive factors that affect postoperative functional outcome. RESULTS: The neurological states at last follow-up were improved in 16 patients (23.2%), unchanged in 47 (68.1%), aggravated in 6 (8.7%). In all patients, the functional outcomes were good in 52 patients (75.4%), fair in 10 (14.5%), poor in 7 (10.1%). Preoperative good neurological state was the strongest positive predictor of good functional outcome (p<0.05). In tumor location, functional outcomes of thoracic tumors were poor than those in cervical and conus medullaris region (p=0.011). High-grade tumor shows poor outcome compare to low-grade tumor (p=0.03). CONCLUSION: The most reliable predicting factor of surgical outcome was the preoperative neurological state. In addition, IMSCTs in thoracic region and high-grade tumor showed relatively bad outcome and had a risk of postoperative morbidity.

An Unusual Form of Coronary Artery Fistula: A Small Aneurysm of Vieussens' Arterial Ring Communicating with the Pulmonary Artery

Vieussens' arterial ring (VAR) is the connection between the conus branch of the right coronary artery and the proximal right ventricular branch of the left anterior descending coronary artery. VARs are found in 48% of the population; however, pathologic VAR is rare. We experienced a case of pathologic VAR that involved a fistula connecting to the main pulmonary artery.

Arteriovenous Fistula of the Filum Terminale Misdiagnosed and Previously Operated as Lower Lumbar Degenerative Disease

Filum terminale arteriovenous fistula (FTAVF) presenting as a cause of failed back surgery syndrome is a rare entity. We report a 48-year-old male patient who presented with clinical features of a conus medullaris/cauda equina lesion. He had upper and lower motor neuron signs in both the lower limbs with autonomic dysfunction. The patient was misdiagnosed and was operated twice earlier for lumbar canal stenosis and disc prolapse. After reviewing his clinical and radiological findings a diagnosis of FTAVF was made. He underwent surgery and there was a significant improvement in his neurological functions. We discuss the case and review the literature on FTAVF's.