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Biomedical subjects

K Chung

Publications and source records attributed to K Chung.

At least 55 records · Page 3Linked to original sources

A novel synthetic method for nanosized crystalline titania for use in the decomposition of dyes.

Photocatalytically active nanocrystalline titania particles were prepared using a hydrothermal process, by controlling the particle size and crystallinity. The crystalline structures and morphologies of the particles were characterized by X-ray diffraction and transmission electron microscopy. The BET method was used to determine the surface area and verify the grain size. To estimate the photocatalytic activity of the synthesized particles, a dye photodegradation experiment was carried out and the activity of the particles was compared with that of conventional titania. The results show that synthesized nanocrystalline titania particles had a higher photocatalytic activity than that of conventional titania. These findings provide a basis for the preparation of more effective and usef ul materials for use in AOP applications.

Catalysis↗

The changes in expression of three subtypes of TTX sensitive sodium channels in sensory neurons after spinal nerve ligation.

Our previous studies showed that the ectopic discharges in injured sensory neurons and mechanical allodynia that developed after spinal nerve ligation were significantly reduced by application of a low concentration of tetrodotoxin (TTX) to the corresponding dorsal root ganglion (DRG) of the ligated spinal nerve. Based on these data, we hypothesized that expression of TTX-sensitive sodium channels is up-regulated in the injured sensory neurons and that such up-regulation plays an important role in the generation of ectopic discharges and thus pain behaviors in spinal nerve ligated neuropathic rats. To test this hypothesis, the present study examined the changes in three subtypes of TTX-sensitive sodium channels in the DRG after spinal nerve ligation. The changes in the total amount of mRNA for alpha-subunits of sodium channel brain type I (type I), brain type II (type II) and brain type III (type III) were determined by RNase protection assays (RPA). The population of DRG neurons expressing type III sodium channel protein was examined by an immunohistochemical method with antibodies to type III sodium channels. In the normal DRG, the level of mRNA for the type I sodium channel is high while that for type II and type III is very low. After spinal nerve ligation, the expression of type III mRNA was significantly increased at 16-h postoperatively (PO), doubled by 3 days PO and then was maintained at this high level until the end of the experiment (7 days PO). By contrast, the amount of mRNA for type I and type II sodium channels started to decrease at 1 day PO and were reduced to 25-50% of the normal control levels by 7 days after nerve ligation. Neurons showing positive immunostaining for type III sodium channels were rare ( approximately 3.2% of total population) in the normal DRG but increased after nerve ligation to 21% and 15% of the total neuronal population by 1 day and 7 days PO, respectively. Type III immunoreactivity was found preferentially in medium to large sized neurons. Thus the majority of neurons with cell bodies having diameters > or =40 microm became type III-positive after nerve ligation. The data indicate that the increased expression of type III sodium channels in axotomized sensory neurons may be the critical factor for the TTX sensitivity of ectopic discharges in injured sensory neurons and thus the generation of ectopic discharges and neuropathic pain behaviors in spinal nerve ligated rats.

Animals↗

Development of purinergic sensitivity in sensory neurons after peripheral nerve injury in the rat.

Purinoceptors are present in the cell bodies as well as in both peripheral and central terminals of many sensory neurons, where they may play a role in sensory transmission, including pain. After peripheral nerve injury at the spinal nerve level, some axotomized afferent neurons develop ongoing discharges (ectopic discharges) that originate in the dorsal root ganglion (DRG). In the present study, we attempted to determine whether or not purinergic sensitivity develops in injured sensory neurons which display ectopic discharges, as well as in silent units. The L(4) and L(5) spinal nerves were ligated in Sprague-Dawley rats. Four to 21 days after the surgery, the DRGs with attached dorsal roots and spinal nerves were removed and ectopic discharges were recorded from teased dorsal root fascicles using an in vitro recording set-up. The results showed that 75.6 and 65.1% of the chronically axotomized DRG neurons displaying ectopic discharges enhanced their activity after application of adenosine 5'-triphosphate (ATP, 1 mM) or alpha,beta-methylene ATP (mATP, 100 microM), respectively. In addition, application of these purinoceptor agonists evoked activity in 7 of 28 axotomized DRG neurons, which did not show ongoing discharges. In contrast, only 1 of 34 DRG neurons acutely isolated from normal rats (no previous spinal nerve ligation) responded to either mATP or ATP. In most of the tested units, mATP-induced enhancement of ectopic discharges was blocked by non-specific P2X receptor antagonists, PPADS or suramin. The data from the present study suggest that purinergic sensitivity develops in DRG neurons after chronic axotomy and that this purinergic sensitivity is likely to be mediated by P2X purinoceptors. This acquired purinergic sensitivity may play an important functional role in the enhancement of ectopic discharges and exacerbation of pain upon sympathetic activation in the neuropathic pain state.

Adenosine Triphosphate↗

Differential expression of alpha1-adrenoceptor subtype mRNAs in the dorsal root ganglion after spinal nerve ligation.

In spinal nerve ligated Lewis strain neuropathic rats, pain behaviors and the rate of ectopic discharges of injured sensory neurons were significantly reduced by systemic injection of phentolamine. A pharmacological study indicated that this adrenergic dependency was mediated by alpha(1)-adrenoceptors (alpha(1)-AR). The development of adrenergic sensitivity in injured sensory neurons might have resulted from changes in adrenoceptor expression as a consequence of changed expression of adrenoceptor genes. This possibility was examined by determining the changes in the mRNA expression of 3 subtypes of alpha(1)-ARs, alpha(1a)-, alpha(1b)-, and alpha(1d)-ARs, in the dorsal root ganglia (DRG) after spinal nerve ligation. The L4 and L5 spinal nerves were tightly ligated in Lewis rats. One week later, the L4 and L5 DRG were collected and RNase protection assay (RPA) and in situ hybridization were performed. In the DRG of unoperated rats, a moderate amount of alpha(1a)-AR mRNA was present while the amount of either alpha(1b)-AR or alpha(1d)-AR mRNA was small. After spinal nerve ligation, there was a significant increase in the amount of alpha(1b)-AR mRNA in the nerve ligated DRG as measured by RPA. The amount of alpha(1a)-AR mRNA was decreased to 20% of the normal level while that of alpha(1d)-AR mRNA did not change. The in situ hybridization study showed that the number of alpha(1b)-AR mRNA positive neurons increased in spinal nerve ligated DRG, confirming the results of RPA study. These data suggest that the up-regulated expression of alpha(1b)-AR mRNA in axotomized DRG neurons may play an important role in the development of adrenergic sensitivity in injured sensory neurons and thus contribute to the sympathetically maintained pain in spinal nerve ligated neuropathic Lewis rats.

Animals↗

Ion channels associated with the ectopic discharges generated after segmental spinal nerve injury in the rat.

In an attempt to identify important ion channels contributing to the generation of ectopic discharges, the present study examined the effects of ion channel blockers on ectopic discharges of injured sensory neurons after spinal nerve ligation. The main focus of the study was to examine the effect of the sodium channel blocker, tetrodotoxin (TTX), in order to identify important subtype(s) (i.e. TTX-sensitive and TTX-resistant) of sodium channels that are involved in ectopic discharge generation. In addition, the effects of potassium and calcium channel blockers were also tested for comparison with the results of previous studies. The dorsal root ganglion (DRG) of the injured segment was removed along with the dorsal root (DR) and the spinal nerve 7-14 days after spinal nerve ligation in the rat. The tissue was placed in an in-vitro recording chamber consisting of multiple compartments that were independently perfused with 35 degrees C artificial cerebrospinal fluid (ACSF). Single unit recordings were made from teased DR fibers. Once a spontaneously active unit was found and characterized, ACSF containing a channel blocker was perfused to the DRG, the site where almost all ectopic discharges originate after spinal nerve ligation. All the recorded spontaneously active units were found to be Abeta and Adelta fibers (no C fibers were detected). Perfusion of the DRG with a sodium channel blocker (lidocaine) at a dose much less than that required to block conduction of action potentials, significantly inhibited ectopic discharges in all recorded fibers. In addition, ectopic discharges were inhibited by TTX perfused to the DRG at a dose much lower (average of 22.1 nM) than that required to block TTX-resistant subtypes of sodium channels. The data suggest that TTX-sensitive sodium channels are likely to be involved in the generation of ectopic discharges. The present study also confirmed the results of previous studies on the additional potential roles of potassium and calcium channels, thus suggesting that multiple ion channels are likely to be involved in the generation of ectopic discharges.

4-Aminopyridine↗

Sympathetic sprouting in the dorsal root ganglion after spinal nerve ligation: evidence of regenerative collateral sprouting.

It is well documented that there is an increase in the number of sympathetic fibers within the dorsal root ganglion (DRG) after a peripheral nerve injury. The present study examined the numbers and distribution of sympathetic fibers in the DRG and their sprouting routes by utilizing various surgical manipulations and retrograde tracing and immunohistochemical staining methods in spinal nerve-ligated neuropathic rats. The appearance of many double immunostained fibers with antibodies to tyrosine hydroxylase (TH) and growth associated protein-43 (GAP-43) in the L5 DRG 1 week after L5 spinal nerve ligation, indicated sprouting of sympathetic fibers. The confined location of early sprouting sympathetic fibers in the distal half of the L5 DRG confirmed that sprouting fibers come primarily from the injured spinal nerve. A second cut proximal to the previously ligated L5 spinal nerve -- a process which would transect the regenerating sympathetic fibers extending from the injury site -- did not change the density of sympathetic fibers in the L5 DRG. When retrograde tracers (fast blue and diamidino yellow) were injected into the L5 spinal nerve and DRG, respectively, the number of double-labeled sympathetic postganglionic neurons was greatly increased after spinal nerve ligation, suggesting the increased number of sympathetic neurons projecting to both the spinal nerve and DRG. All these results indicate that many sympathetic fibers in the DRG are regenerating branches that are sprouting from the proximal part of the injured spinal nerve (regenerative collateral sprouting).

Animals↗

Effector function of resting T cells: activation of synovial fibroblasts.

Synovial tissue in rheumatoid arthritis is characterized by infiltration with large numbers of T lymphocytes and APCs as well as hyperplasia of synovial fibroblasts. Current understanding of the pathogenesis of RA includes the concept that synovial fibroblasts, which are essential to cartilage and bone destruction, are regulated by cytokines derived primarily from monocyte-macrophage cells. Recently it has been found that synovial fibroblasts can also function as accessory cells for T cell activation by superantigens and other stimuli. We have now found that highly purified resting T cells, even in the absence of T cell mitogens, induce activation of synovial fibroblasts when cocultured for 6-24 h. Such activation was evident by induction or augmentation of mRNA for stromelysin, IL-6, and IL-8, gene products important in joint inflammation and joint destruction. Furthermore, increased production of IL-6 and IL-8 was quantitated by intracellular cytokine staining and flow cytometry. This technique, previously used for analysis of T cell function, was readily adaptable for assays of synovial fibroblasts. Resting T cells also induced synovial fibroblasts to produce PGE(2), indicating activation of expression of the cyclooxygenase 2 gene. Synergy was observed between the effects of IL-17, a cytokine derived from stimulated T cells that activates fibroblasts, and resting T lymphocytes. Various subsets of T cells, CD4(+), CD8(+), CD45RO(+), and CD45RA(+) all had comparable ability to induce synovial fibroblast activation. These results establish an Ag-independent effector function for resting T cells that is likely to be important in inflammatory compartments in which large numbers of T lymphocytes and fibroblasts can come into direct contact with each other.

Adjuvants, Immunologic↗

Identification of carmine allergens among three carmine allergy patients.

BACKGROUND: There have been several reports of carmine allergy; however, identification of the responsible carmine allergens has not been widely documented. METHODS: Three female patients presented with a history of anaphylaxis and/or urticaria/angioedema after ingestion of carmine-containing foods. All three patients had 4+ skin prick tests to carmine. Among them, two patients were confirmed to have carmine allergy by blinded, placebo-controlled food challenges to carmine. SDS-PAGE of cochineal insects and carmine, immunoblotting for IgE antibody with sera from all three patients, and immunoblotting inhibition with carmine were performed. RESULTS: SDS PAGE of minced cochineal insects revealed several protein bands of 23-88 kDa. Several of these bands were variably recognized by our three patients' sera, and this reactivity was inhibited by carmine. Although no protein bands could be visualized on SDS-PAGE of carmine in Coomassie brilliant blue staining, three protein bands were recognized by two of the three patients' serum. CONCLUSIONS: These results suggest that commercial carmine retains protein-aceous material from the source insects. These insect-derived proteins (possibly complexed with carminic acid) are responsible for IgE-mediated carmine allergy. Patient reactivity to these proteins may vary.

Administration, Oral↗

Effect of sandblasting on the bond strength of the bondable molar tube bracket.

This study examined the effect of surface treatment with sandblasting on bracket bonding strength. Extracted human tooth, base metal alloy and porcelain surfaces were treated with sandblasting. The bracket bonding strengths of sandblasted surfaces were evaluated and compared with the controls and etched enamel surfaces. Morphological observation of the treatment surfaces and the failure sites was conducted. Statistical analysis included one-way analysis of variance (ANOVA) and a Scheffe's F-test at the 95% confidence level was performed. The results indicated that mean bond strength values ranged from 3.6 MPa (the untreated control) to 20.4 MPa for the etched enamel surface. No statistically significant differences were determined among the etched enamel, sandblasted metal and sandblasted porcelain surfaces (P > 0.05). Most debonding specimens failed at either the resin-tooth interface or within the adhesive. In conclusion, sandblasting the metal and porcelain surfaces obtained a bracket bond strength comparable with that with the etched enamel surface.

Acid Etching, Dental↗

Influence of estrogen status on endosseous implant osseointegration.

PURPOSE: This retrospective study tested the hypothesis that postmenopausal women have lower rates of osseointegration of endosseous implants than premenopausal women and male controls. The role of estrogen replacement therapy (ERT) was also evaluated. PATIENTS AND METHODS: Review of medical records allowed identification of patients who had received endosseous implants. Patients with concurrent illness, a smoking or ethanol use history, or metabolic bone disease were excluded. Five groups of subjects were identified: 1) 168 postmenopausal women without ERT; 2) 75 postmenopausal women supplemented with ERT; 3) 114 premenopausal women; 4) 59 men younger than 50 years; and 5) 110 men older than 50 years. Successful osseointegration was defined as stability at uncovering using a manual torque wrench and was confirmed radiographically. Failure rate comparisons were made between groups using both Fisher's exact tests and Poisson regression models. RESULTS: Postmenopausal women without ERT had the highest maxillary failure rate (13.6%) which was significantly greater than for premenopausal women (6.3%, P =.039) and for men older than 50 (7.6%, P =.051). Although the maxillary failure rate of unsupplemented postmenopausal women was greater than for ERT supplemented women (8.1%), the comparison did not reach statistical significance (P =.17). The maxillary failure rate was similar between men younger than 50 years and those older than 50 years (6.3 vs 7.6%, not significant) Mandibular implant failures in all groups showed no statistically significant differences. CONCLUSION: The effect of postmenopausal estrogen status on compromised implant healing was shown in the maxilla but not in the mandible. Unsupplemented postmenopausal women had the highest failure rate. Although a statistical difference was not achieved, ERT reduced the maxillary failure rate by 41%. These results suggest that estrogen deficiency and the resultant bony changes associated with menopause may be risk factors for endosseous implant failure in the maxilla.

Age Factors↗

The effect of lumbar sympathectomy in the spinal nerve ligation model of neuropathic pain.

To evaluate the sympathetic dependency of pain behaviors in an animal model of neuropathic pain, the effect of surgical sympathectomy on the mechanical sensitivity of the hindpaw was examined in rats with L5 spinal nerve ligation. Mechanical sensitivity was determined by measuring foot withdrawal thresholds to mechanical stimulation with von Frey filaments applied to the base of the third or fourth toe. Tight ligation of the segmental L5 spinal nerve led to the development of mechanical hypersensitivity in the hindpaw. The effects of 2 different procedures of surgical lumbar sympathectomy on mechanical hypersensitivity were compared, limited (resection of sympathetic chain/ganglia L2 to L4 segments) and extensive (resection of L2 to L6 segments) sympathectomies. Mechanical hypersensitivity produced by L5 spinal nerve ligation was partially but significantly reduced by both sympathectomy procedures. In a separate group of rats, the L5 spinal nerve was ligated while irritating the neighboring L4 spinal nerve. This procedure produced a lesser degree of mechanical hypersensitivity, and subsequent sympathectomy had no effect on these animals. These data suggest that sympathectomy is effective in this model only when the animals show severe mechanical hypersensitivity.

Journal Article↗

Female steroid hormones modulate receptors for nerve growth factor in rat dorsal root ganglia.

Calcitonin gene-related peptide (CGRP) is a vasodilatory peptide, and it is primarily synthesized in dorsal root ganglia (DRG). Plasma CGRP levels increase during pregnancy and with steroid hormones, and nerve growth factor (NGF) stimulates calcitonin/CGRP promoter and CGRP synthesis in DRG. We previously showed that CGRP levels in DRG were stimulated with steroid hormone treatments in vivo but not in vitro. Thus, the stimulation of CGRP by these hormones may be indirect through the upregulation of NGF effects. We hypothesized that the female sex steroid hormones upregulate NGF receptors, trkA and p75(NTR), in DRG. We examined the effects of 17 beta-estradiol (E(2)) and progesterone (P(4)) on NGF receptors in DRG obtained from ovariectomized (ovx) rats. Groups of 4 ovx rats were injected s.c. with 5 microg E(2), 4 mg P(4), or 5 microg E(2) + 4 mg P(4) in 0.2 ml sesame oil or injected with oil only and were killed at 6, 24, and 48 h. In addition, ovx rats were also injected s.c. with varying doses (0.2, 1.0, 5.0, 25 microg) of E(2) (0.5, 1.5, 4, 10 mg) P(4), and (5 microg) E(2) + (0.5, 1.5, 4.0, 10 mg) P(4) in 0.2 ml sesame oil, or vehicle, and killed at 6 (for E(2)) or 24 (for P(4) and E(2) + P(4)) h. Furthermore, groups of ovx rats were also killed at 12 and 24 h; 3 and 7 days; 2, 4, and 6 wk after ovariectomy. The DRGs were collected from all groups and then processed for Western immunoblotting to examine both trkA and p75(NTR) levels. Estradiol increased trkA at 6 h but not p75(NTR). Progesterone caused upregulation of trkA and p75(NTR) at 6 and 24 h. 17 beta-Estradiol + P(4) increased trkA at 6 and 24 h and p75(NTR) at all time points examined. One microgram of E(2) increased trkA but did not affect p75(NTR) levels. Progesterone at 4 and 10 mg upregulated trkA but only 10 mg P(4) increased p75(NTR). Five micrograms of E(2) coinjected with P(4) at 1.5 and 4 mg increased trkA, while p75(NTR) receptor was upregulated when coinjected with P(4) at 1.5 to 10 mg. The ovariectomy caused a decrease in trkA receptors compared to proestrus rats, and these decreases were significant by 6 wk, but surprisingly p75(NTR) increased at 2 wk after ovariectomy. 17 beta-Estradiol increased trkA but not p75(NTR) receptors in DRG, whereas P(4) caused increases in both trkA and p75(NTR) in DRG. In addition, the combination of these steroid hormones had more effect on both receptors than either hormone alone. Thus, we concluded that high levels of female steroid hormones such as those due to pregnancy or hormonal replacement therapy could increase NGF receptor expression in DRG that carry more NGF to elevate the CGRP synthesis in these groups. We suggested that the regulation of NGF receptors by ovarian steroids may underlie steroidal regulation of other factors such as CGRP.

Animals↗

Role of flexion-extension radiographs in blunt pediatric cervical spine injury.

OBJECTIVE: To determine whether flexion-extension cervical spine radiography (FECSR) is abnormal in children who have sustained blunt cervical spine injury (CSI) when standard cervical spine radiography (SCSR) demonstrates no acute abnormalities. METHODS: This was a blinded radiographic review of 129 patients < or = 16 years of age evaluated at an academic pediatric trauma center during July 1990-March 1996. All patients had SCSR (anteroposterior/lateral views) and FECSR performed for a trauma-related event within seven days of injury. RESULTS: Of 46 patients without acute abnormalities on SCSR, one patient (with final clinical diagnosis of "no CSI") had acute abnormalities on FECSR (95% CI = 0.06% to 11.5%). Of 50 patients with isolated loss of lordosis on SCSR, no patient had acute abnormalities on FECSR (95% CI = 0% to 5.8%). The FECSR review revealed no acute abnormalities in 75 of 83 patients (90.4%) with suspicious findings for CSI viewed on SCSR (95% CI = 81.9% to 95.7%). Complications during FECSR were noted in one patient with transient paresthesias (0.8%) (95% CI = 0.02% to 4.2%). CONCLUSIONS: In children who underwent acute radiographic evaluation of blunt cervical spine trauma, FECSR was unlikely to be abnormal when no acute abnormality or isolated loss of lordosis was evident on SCSR. In a subset of patients with suspicious findings for occult CSI on SCSR, FECSR was useful in ruling out ligamentous instability in the acute, posttrauma setting.

Adolescent↗

Relationship between ultrastructure and the nanoindentation properties of intramuscular herring bones.

The nanoindentation technique was used to characterize the indentation modulus of intramuscular herring bone (Clupea harengus) along its length, from early to fully mineralized regions. Both the indentation modulus and modulus anisotropy ratio, indentation modulus longitudinally/indentation modulus transversely, increased nonmonotonically with mineralization, from 1.1 in the early stages of mineralization to 2.1 in the fully mineralized region. The indentation modulus in the fully mineralized region decreased from 19.9+/-2.0 GPa in the longitudinal direction to 11.4+/-1.5 GPa in the transverse directions. In the earliest stages of mineralization, the indentation modulus was 3.8+/-0.7 GPa in the longitudinal direction and 3.5+/-0.3 GPa in the transverse direction. High-intensity synchrotron x rays were used to examine two parameters of crystal texture, the coherence length and the angular spread. Low angular spread was seen along the c axis of bone crystallite. However, the large angular spread observed along the (300) plane indicated an imperfection of crystallite periodicity in the direction perpendicular to the longitudinal axis in the bone. The relatively high coherence length was related to the low angular spread. In general, the indentation modulus increased with increasing crystallite size, but the indentation modulus decreased with increasing crystallite size along the (300) plane.

Analysis of Variance↗

Applications of low-cost, dual-fraction dust samplers.

Porous polyurethane foams provide a low-cost method for separating dust into health-related fractions in accordance with recognized sampling conventions. A number of dust sampling instruments that make use of foam selectors have been described in recent literature, but practical experiences of using these instruments in real workplaces have not been widely reported. An IOM inhalable dust sampler incorporating a respirable-fraction selector foam was evaluated in a range of industries, for general occupational dust monitoring. The key issues addressed were those that determine the practicability of the instrument, such as limitations on particulate loading, losses or movements of particles during transportation of samples, and equivalence with conventional respirable dust sampling methods. The new sampler was found to be satisfactory in all these respects. The minor problems experienced have been addressed during the design of the production version of the foam cassette, which is available as an accessory for the existing IOM inhalable dust sampler. The key advantage of the new dust sampler is that it measures both inhalable and respirable dust concentrations in a single sample (hence the name: dual-fraction dust sampler). Therefore, it saves both time and money in industries where both inhalable and respirable dust are routinely monitored.

Air Pollutants, Occupational↗

Experimental and modeling evaluation of upward and downward velocities in the coaxial flotation column.

This study was conducted to show the influence of upward velocity in the inner column and downward velocity in the outer column of the coaxial cylinder-type flotation column on the solids removal efficiency, solids concentration in the treated water, and so on. The SIMPLE (Semi-Implicit Method for Pressure Linked Equation) solution was applied to the coaxial flotation column to simulate the velocity vectors of the elements of water flowing in the column. The effects of solids loading and residence time in the agglomerate separation zone on the solids removal efficiency were also tested. In the pilot scale coaxial DAF column experiments with solids concentration of 1,000-2,000 mg of SS per liter and solids loading less than 350 kg/m2/day, approximately 90% of the solids removal efficiencies were obtained using the upward velocity of up to 110 cm/min in the contact zone of the inner column and the downward velocity of up to 30 cm/min in the outer column. In the simulation, similar results were observed as in the experiments. The solids loading in the excess of 350 kg/m2/day caused the instability of the sludge float layer and aggravated the quality of the treated water.

Air↗

Purification and cDNA cloning of salmorin that inhibits fibrinogen clotting.

A new protein, salmorin, that inhibits fibrinogen clotting was purified to homogeneity from the snake venom of Agkistrodon halys brevicaudus. Salmorin was characterized to be a heterodimeric protein composed of 15 kDa and 14 kDa subunits. Purified salmorin inhibited not only thrombin-induced fibrinogen clotting but also factor Xa-induced prothrombin activation. Experimental evidence indicated that the hetero-dimeric protein does not bind to the thrombin catalytic site but binds to thrombin and prothrombin exosites. Analyses of the cDNA sequences encoding the two separate polypeptide chains revealed that the mature subunits are composed of 131 and 122 amino acids, respectively. In the isolated cDNAs, N-termini of both chains are preceded by hydrophobic signal peptides of 23 residues. The deduced amino acid sequence exhibited considerable identity with other snake venom C-type lectin-like proteins derived from various snake venoms.

Agkistrodon↗

Low dose of tetrodotoxin reduces neuropathic pain behaviors in an animal model.

We hypothesize that the accumulation of tetrodotoxin (TTX) sensitive sodium channels in injured dorsal root ganglion (DRG) neurons plays a critically important role in the generation of ectopic discharges and mechanical allodynia after peripheral nerve injury. Using the segmental spinal nerve (L5) ligation model of neuropathic pain, this hypothesis was tested by examining the effect of TTX on the mechanical sensitivity of the affected hind paw. Various concentrations of TTX were applied topically to the L5 DRG by using chronically implanted polyethylene tubing. The data showed that application of TTX at low doses (12.5-50 nM), which are far less than those needed for blocking action potential conduction, produced a significant elevation of mechanical threshold in the paw for foot withdrawals, a sign of reduced allodynic behaviors. The data suggest that TTX-sensitive subtypes of sodium channels play an important role in maintaining allodynic behaviors in an animal model of neuropathic pain.

Action Potentials↗