Tramadol as a Voltage-Gated Sodium Channel Blocker ofPeripheral Sodium Channels Na v 1.7 and Na v 1.5

Tramadol is an opioid analog used to treat chronic and acute pain. Intradermal injections of tramadol at hundreds of millimoles have been shown to produce a local anesthetic effect. We used the whole-cell patch-clamp technique in this study to investigate whether tramadol blocks the sodium current in HEK293 cells, which stably express the pain threshold sodium channel Na v1.7 or the cardiac sodium channel Na v1.5. The half-maximal inhibitory concentration of tramadol was 0.73 mM for Na v1.7 and 0.43 mM for Na v1.5 at a holding potential of –100 mV. The blocking effects of tramadol were completely reversible. Tramadol shifted the steady-state inactivation curves of Na v1.7 and Na v1.5 toward hyperpolarization. Tramadol also slowed the recovery rate from the inactivation of Na v1.7 and Na v1.5 and induced stronger use-dependent inhibition. Because the mean plasma concentration of tramadol upon oral administration is lower than its mean blocking concentration of sodium channels in this study, it is unlikely that tramadol in plasma will have an analgesic effect by blocking Na v1.7 or show cardiotoxicity by blocking Na v1.5. However, tramadol could act as a local anesthetic when used at a concentration of several hundred millimoles by intradermal injection and as an antiarrhythmic when injected intravenously at a similar dose, as does lidocaine.

Induction of Peptide-specific CTL Activity and Inhibition of Tumor Growth Following Immunization with Nanoparticles Coated with Tumor Peptide-MHC-I Complexes

Tumor peptides associated with MHC class I molecules or their synthetic variants have attracted great attention for their potential use as vaccines to induce tumor-specific CTLs. However, the outcome of clinical trials of peptide-based tumor vaccines has been disappointing. There are various reasons for this lack of success, such as difficulties in delivering the peptides specifically to professional Ag-presenting cells, short peptide halflife in vivo, and limited peptide immunogenicity. We report here a novel peptide vaccination strategy that efficiently induces peptide-specific CTLs. Nanoparticles (NPs) were fabricated from a biodegradable polymer, poly(D,L-lactic-co-glycolic acid), attached to H-2Kb molecules, and then the natural peptide epitopes associated with the H-2K b molecules were exchanged with a model tumor peptide, SIINFEKL (OVA 257-268 ). These NPs were efficiently phagocytosed by immature dendritic cells (DCs), inducing DC maturation and activation. In addition, the DCs that phagocytosed SIINFEKL-pulsed NPs potently activated SIINFEKL-H-2K b complex-specific CD8 + T cells via cross-presentation of SIINFEKL. In vivo studies showed that intravenous administration of SIINFEKL-pulsed NPs effectively generated SIINFEKLspecific CD8 + T cells in both normal and tumor-bearing mice. Furthermore, intravenous administration of SIINFEKL-pulsed NPs into EG7.OVA tumor-bearing mice almost completely inhibited the tumor growth. These results demonstrate that vaccination with polymeric NPs coated with tumor peptide-MHC-I complexes is a novel strategy for efficient induction of tumor-specific CTLs.

Immunotherapy of Autoimmune Diseases with Nonantibiotic Properties of Tetracyclines

Tetracyclines, which have long been used as broad-spectrum antibiotics, also exhibit a variety of nonantibiotic activities including anti-inflammatory and immunomodulatory properties.Tetracyclines bind to the 30S ribosome of the bacteria and inhibit protein synthesis.Unlike antimicrobial activity, the primary molecular target for the nonantibiotic activity of tetracycline remains to be clarified. Nonetheless, the therapeutic efficacies of tetracyclines, particularly minocycline and doxycycline, have been demonstrated in various animal models of autoimmune disorders, such as multiple sclerosis, rheumatoid arthritis, and asthma.In this study, we summarized the anti-inflammatory and immunomodulatory activities of tetracyclines, focusing on the mechanisms underlying these activities. In addition, we highlighted the on-going or completed clinical trials with reported outcomes.

Immunotherapy of Autoimmune Diseases with Nonantibiotic Properties of Tetracyclines

Tetracyclines, which have long been used as broad-spectrum antibiotics, also exhibit a variety of nonantibiotic activities including anti-inflammatory and immunomodulatory properties.Tetracyclines bind to the 30S ribosome of the bacteria and inhibit protein synthesis.Unlike antimicrobial activity, the primary molecular target for the nonantibiotic activity of tetracycline remains to be clarified. Nonetheless, the therapeutic efficacies of tetracyclines, particularly minocycline and doxycycline, have been demonstrated in various animal models of autoimmune disorders, such as multiple sclerosis, rheumatoid arthritis, and asthma.In this study, we summarized the anti-inflammatory and immunomodulatory activities of tetracyclines, focusing on the mechanisms underlying these activities. In addition, we highlighted the on-going or completed clinical trials with reported outcomes.

Fragmented Split-Thickness Skin Graft Using a Razor Blade in Burn Induced Diabetic Foot

Diabetic patients have an increased risk of burn injuries on foot. Because of their diabetic neuropathy, they could contact with hot water or warming device without being aware of it. Split-thickness skin graft (STSG) is successful in treatment of various wound types; however, donor site wounds are sometimes problematic, and complications such as pain and impaired healing often occur. Although, donor site wounds in healthy young individuals can rapidly heal without complications, the wound-healing capacity of elderly patients or those with a comorbidity has been reported to be low. The dermatome is the most commonly used tool because it can harvest a large skin graft in one attempt. However, it is difficult to harvest tissues if the area is not flat. Furthermore, because the harvested skin is usually rectangular, additional skin usually remains after skin grafting. Therefore, use of razor blade and fragmented STSG on a large defect area is advantageous for harvesting a graft with a desired size, shape, and thickness. From January 2018 to July 2018, fragmented STSG was used in 9 patients who suffered from burn induced open wound on foot with diabetic neuropathy. With this approach, healing process was relatively rapid. The mean age of patients was 70 (57∼86 years) and all of 9 patients had diabetes mellitus type 2. In all patients, the skin graft on the defect site healed well and did not result in complications such as hematoma or seroma.

Polymeric Nanoparticles Containing Both Antigen and Vitamin D₃ Induce Antigen-Specific Immune Suppression

The active form of vitamin D3, 1,25-dihydroxyvitamin D₃ (aVD₃), is known to exert beneficial effects in the treatment of autoimmune diseases because of its immunosuppressive effects. However, clinical application of aVD₃ remains limited because of the potential side effects, particularly hypercalcemia. Encapsulation of aVD₃ within biodegradable nanoparticles (NPs) would enhance the delivery of aVD₃ to antigen presenting cells, while preventing the potential systemic side effects of aVD₃. In the present study, polymeric NPs containing ovalbumin (OVA) and aVD₃ (NP[OVA+aVD₃]) were prepared via the water-in-oil-in-water double emulsion solvent evaporation method, after which their immunomodulatory effects were examined. Bone marrow-derived immature dendritic cells (DCs) treated with NP(OVA+aVD₃) did not mature into immunogenic DCs but were converted into tolerogenic DCs, which express low levels of co-stimulatory molecules and MHC class II molecules, produce lower levels of pro-inflammatory cytokines while increasing the production of IL-10 and TGF-β, and induce the generation of Tregs. Intravenous injection with NP(OVA+aVD₃) markedly suppressed the generation of OVA-specific CTLs in mice. Furthermore, OVA-specific immune tolerance was induced in mice orally administered with NP(OVA+aVD₃). These results show that biodegradable NPs encapsulating both antigen and aVD₃ can effectively induce antigen-specific immune suppression.

Publication rate of presentations at Korean plastic surgery meetings: The R&R Forum, KSAPS, and KSPRS (2011–2015)

BACKGROUND: Since the initial Research and Reconstruction Forum (R&R Forum) in 2011, the R&R Forum, Korean Society for Aesthetic Plastic Surgery (KSAPS), and Korean Society of Plastic and Reconstructive Surgeons (KSPRS) have held annual meetings. This study was conducted to provide updated information on the publication rate of presentations at those meetings. METHODS: Plastic surgery–related abstracts presented at the R&R Forum, KSAPS, and KSPRS between 2011 and 2015 were collected. The sessions were divided into free papers, posters, and e-presentations (or e-posters) for each annual meeting. Abstract publication status was confirmed through PubMed, Google Scholar, the KCI-Korean Journal Database, and the KMbase database. RESULTS: In total, 2,335 abstracts were presented in the free paper, poster, and e-presentation sessions. Of these, 622 (26.6%) were published. The overall publication rates were 240 of 684 abstracts (35.1%) presented at the R&R Forum, 56 of 216 abstracts (25.9%) presented at the KSAPS meetings, and 326 of 1,435 abstracts (22.7%) presented at the KSPRS meetings. In terms of specific annual meetings, the 2014 R&R Forum had the highest publication rate (39.9%), followed by the 2015 KSAPS (31.0%) and the 2015 KSPRS (28.8%). CONCLUSIONS: Scientific researchers present diverse results at these professional meetings, with a focus on innovative surgical techniques and improved surgical outcomes. This is our second study on this topic. Despite its limitations, this study indirectly shows that the recognition of Korean plastic surgeons and the quality of the annual meetings of Korean societies of plastic surgery have risen to the global level.

Distally-based free anterolateral thigh flap with a modified vena comitans

With the recent development in microsurgery, the use of a perforator flap has been widely implemented. If the length of the ALT flap pedicle is insufficient despite adequate preoperative planning, pedicle length extension is necessary. We planned for a reverse ALT free flap using the distal vessel of the descending branch for pedicle length extension in the case of ALT perforator branch originating from the proximal portion of the descending branch. For the management of venous congestion, the distal venae comitantes were anastomosed to the proximal venous stump in an antegrade manner, successfully resolving the venous congestion. Modified reverse-flow ALT free flap, wherein the venae comitantes are anastomosed to the proximal vein stump, is a good option that allows for relatively simple pedicle extension within the same operative field when securing an adequate pedicle length is difficult because of the origin of the perforator from the proximal descending branch, unlike the initial surgical plan.

Squamous cell carcinoma identified in a thick-walled epidermal cyst with a recurrent ulcer

No abstract available.

Patterns in the amount of discharge at split-thickness skin graft donor sites

BACKGROUND: Split-thickness skin grafts (STSGs) are commonly used in the reconstruction of skin defects induced by trauma or burns. Although STSGs are used to successfully treat various wound types, donor site wounds can be challenging, and complications often develop. Therefore, optimal donor site dressings are required. In this study, we introduce an evidence base for patterns in how the discharge amount decreases over time, with the goal of providing insights into the selection of dressing materials. METHODS: Twenty patients with burns who received STSGs harvested from the thigh between January 2016 to April 2017 were prospectively reviewed. A donor site dressing with foam was changed daily. The weight of the foam dressing was measured before and after placement on the donor site. The wound area was calculated using Visi-Trak. The mean weight of the discharge amount per unit area (g/10 cm2) was calculated. RESULTS: The mean weight of the discharge amount per unit area (g/10 cm2) decreased from 3.84 to 2.02 (P < 0.05) and 1.09 (P < 0.05) on postoperative days 5 and 10, respectively. It further decreased to 0.61 by postoperative day 14. CONCLUSIONS: To prevent infections induced by donor site leakage, the use of highly-absorptive foam materials until 5 days after the operation is beneficial. Moreover, hydrocolloid or highly-absorptive foam materials can be used to promote re-epithelialization of the donor site after 5 days postoperatively. For re-epithelialization and wound protection, it is effective to use hydrocolloid materials starting on postoperative day 10.

Vastus intermedius–anterolateral thigh chimeric free flap for lower extremity reconstruction

No abstract available.

Comparison of neuropsychological characteristics inpatients with amnestic and vascular mild cognitive impairment / 中华老年医学杂志

Objective To identify the differences inneuropsychological characteristics between amnestic(AMCI)and vascular mild cognitive impairment(VMCI).Methods Totally 297 old community residents with mild cognitive impairment(MCI)were divided into amnestic MCI(AMCI)and vascular MCI(VMCI)subgroup from Guangzhou MCI prevalence survey.The elderly with MCI were interviewed and tested with the Chinese version of Montreal Cognitive Assessment(MoCA),the Mini-Mental state examination(MMSE),Auditory Verbal Learning Test(AVLT),the Clinical Dementia Rating scale(CDR),Functional Activity Questionnaire(FAQ),the Modified Hachinski Ischemic Scale(M-HIS),Center for Epidemiologic Studies(CES-DC)to evaluate neuropsychological characteristics.Results AMCI versus VMCI group showed that the total scores of MoCA were(9.63±5.17 vs.9.98±6.02),total scores of MMSE were(16.90±4.84 vs.16.90±6.19),AVLT immediate memory was(2.35±1.39 vs.2.91±1.84),AVLT delayed recall was(2.23±2.09 vs.2.47±2.20),AVLT delayed recognition was(7.33±3.98 vs.6.85±4.02)and total scores of CDR(0.5 vs.0.5),with no differences between the 2 groups(all P>0.05).Based on MoCA survey,AMCI versus VMCI group showed statistically significant differences(all P<0.05)in parameters of visual space and execution(0.71±1.02 vs.0.92±1.26),language function(0.34±0.56 vs.0.50±0.80)and abstract thinking(0.25±0.49 vs.0.15±0.43),but based on MMSE survey,no difference was found in the various cognitive domains between the two groups.The AMCI versus VMCI group showed statistically significant differences(all P<0.05)in parameters of CES-DC scale(1.75±4.27 vs.2.76±6.72),FAQ scale(4.42±4.66 vs.8.71±7.03),M-HIS scale(0.40±0.64 vs.7.59±3.53).Conclusions There is no significant difference in general cognitive impairment between AMCI and VMCI,but the visual space and execution,language function are more impaired in AMCI than VMCI,and the abstract thinking,social function are more impaired with more depressive symptoms in VMCI than in AMCI.

A control study of cognitive function in patients with treatment-resistant depression and first-episode depression / 天津医药

Objective To compare the cognitive functions between patients with treatment-resistant depression and first-episode depression. Methods A total of 80 major depressive disorder patients admitted in our hospital from March 2015 to December 2016 were included in this study. The patients were divided into treatment-resistant depression group (n=40) and first-episode depression group (n=40). Another 40 healthy individuals were used as the control group. The basic data of patients were collected, and Hamilton depression scale (HAMD)-17 was used to assess the severity of the disease. The performing functions were assessed by trail marking test and stroop color-word test. The attention functions were assessed by digital span test. Memory functions were assessed by Hopkins verbal learning test revise (HVLT-R). After treatment for 6 months, cognitive functions were assessed again in first-episode depression group. Results Compared with control group, the scores of trail marking test (TMT) increased, while the scores of digital span test, stroop color-word test, stroop color-colorword test, HVLT-R reduced in treatment-resistant depression group and first-episode depression group ( P<0.05). The scores of TMT, HAMD-17 were lower in first-episode depression group than those of treatment-resistant depression group (P < 0.05). There were no significant differences in other indexes between groups. After six months treatment, the trail marking test score and HAMD-17 reduced, but digital span test, stroop color-word test increased in first-episode depression group (P<0.05). Conclusion The cognitive function damages severely in patients with treatment-resistant depression and first-episode depression, but there is no obvious difference in severity between two groups of patients.

The Correlation of Differences in the Ocular Component Values with the Degree of Myopic Anisometropia

PURPOSE: To determine the relationship between the differences in the ocular component values with the degree of anisomyopia. METHODS: Refraction, corneal power (CP), and biometry were examined in 50 myopic adults with refractive differences (RD) over 1.50 diopters (D). Ocular components were measured by ultrasound biometry and keratometry. The correlation between the differences in the ocular component values with the degree of anisomyopia was analyzed by linear regression analysis. RESULTS: Among 50 adults with anisomyopia, 5 had RD from 1.50 to 2.99 D, 11 had RD from 3.00 to 3.99 D, 9 had RD from 4.00 to 5.99 D, 12 had RD from 6.00 to 7.99 D, 7 had RD from 8.00 to 11.99 D, and 6 had > or =12.00 D. There was no significant correlation between the ocular components (CP, crystalline lens thickness [LT], and anterior chamber depth [ACD], and the length from the cornea to the posterior surface of the lens [ACD + LT]) and the RD (p > 0.05). The RD showed a significantly positive correlation with vitreous chamber depth (VCD), and axial length (r = 0.963, p < 0.0001). CONCLUSIONS: The severity of anisomyopia was not correlated with the between-eye differences in the anterior chamber values of the eye (CP, ACD, LT, ACD + LT). The severity of anisomyopia was significantly correlated with the between-eye differences in VCD.

Human Skin Safety Test of Green Tea Cell Extracts in Condition of Allergic Contact Dermatitis

Various kinds of positive effects of green tea extracts had been studied for long time which included anti-inflammation, anti-aging, and cardiometabolic effects. Although topical steroid and non-steroidal calcineurin inhibitors may control clinical symptoms of allergic contact dermatitis, some of patients also present allergic reaction to these topical agents. Therefore, we have tried green tea extracts for managing this skin disorder with expectation of anti-inflammatory effect without potential side effects including skin irritation and toxic responses. The toxicity test of green tea extract also did not show any sign of irritation in the skin throughout the test period. Moderate severity of allergic contact dermatitis presented satisfactory clinical outcome at second week follow-up which was final visit of outpatient. This result mean that green tea extract has a positive effect for managing allergic contact dermatitis but its potency and efficacy seem to be so not strong enough to control moderate severity allergy skin lesion. In this pilot study, we were able to conclude that green tea cell extracts might be applied for potential anti-inflammatory soaking without skin toxicity.

Treatment of Atopic Dermatitis Associated with Malassezia sympodialis by Green Tea Extracts Bath Therapy: A Pilot Study

Multiple treatment modalities, including topical and systemic corticosteroid and phototherapy, have been used in treatment of patients with atopic dermatitis. However, long-term corticosteroid therapy may have various adverse effects. The purpose of this study was to investigate the therapeutic efficacy and safety of bath therapy using green tea extracts for treatment of patients with atopic dermatitis. A total of four patients with atopic dermatitis were enrolled in this study. A Malassezia multiplex detection kit was used in performance of multiplex PCR on clinical isolates, which confirmed Malassezia sympodialis. Subjects underwent treatment with bath therapy using green tea extracts three times per wk for a period of 4 wk. Assessment using the scoring atopic dermatitis (SCORAD) index, the visual analogue scale for pruritus, and transepidermal water loss was performed weekly. Laboratory tests were performed before and after treatment. All patients showed marked improvement on the mean SCORAD and visual analogue scale, and a significant decrease in the mean values of serum eosinophil counts was observed after treatment. Bath therapy with green tea extract is an effective, safe, and nonsteroidal therapy for treatment of patients with atopic dermatitis associated with Malassezia sympodialis.

Change in Ocular Dimensions with Age in Patients with Emmetropia

PURPOSE: We evaluated changes in ocular dimensions according to age in patients with emmetropia. METHODS: We examined the refraction, corneal curvature, and biometry in 150 subjects from 5 to 75 years old with spherical equivalent refractions under +/-0.75 diopter (D). Ocular dimensions were measured by A-scan ultrasonography and keratometry. We analysed the distribution and change of ocular dimensions according to age (1: 0~19-year-old group, 2: 20~39-year-old group, 3: 40~59-year-old group, 4: 60~79-year-old group). RESULTS: The values for corneal radius (CR), vitreous chamber depth (VCD) and axial length (AL) were highest in group 2. Lens thickness (LT) increased with increasing age, whereas anterior chamber depth (ACD)decreased with increasing age (P<0.05). CR, VCD, AL (P<0.05) and ACD (P=0.10) seem to have higher values in males, while LT seems to have a higher value in females (P=0.06). CONCLUSIONS: Axial length increases with increasing age in subjects aged 0 to 39 years in emmetropia. In subjects aged 40 years or older, axial length becomes smaller with age. In each age group compensational changes to achieve emmetropia according to AL change are shown in ocular dimensions like CR, VCD, ACD, LT.

Comparative Study of the Latissimus Dorsi and Gracilis Muscle Reconstruction for Reanimation of a Paralyzed Face

PURPOSE: The most accepted method for the reanimation of a paralyzed face is the two-stage method that combines cross-face nerve grafting with free-muscle transfer. Although the results of reconstruction with this method are satisfactory, there is an excessive delay between the stages, which prolongs the period of rehabilitation. In order to overcome this drawback, a one- stage, neurovascular free-flap reconstruction method using free neurovascular muscle flaps is introduced. METHODS: From 1994 to 2004, 35 patients with longstanding facial palsy were treated. Fifteen patients underwent the single-stage reconstruction with the latissimus dorsi muscle, and 20 patients underwent the two-stage reconstruction method with the gracilis muscle. We compared the long-term results of the two methods of reconstruction. The mean follow-up period was 28.7 months for one-stage reconstruction, and 35.2 months for the two-stage, respectively. RESULTS: In the patient group of the single stage reconstruction, both mouth corner excursion and animation grade were markedly improved at the final postoperative visit. Moreover, the first muscle contraction occurred earlier in this group, than in the two-stage reconstruction group. However, four patients in the single stage group never achieved a first muscle contraction or mouth corner excursion. CONCLUSION: Facial palsy is a very challenging condition for cosmetic surgeons to deal with. Traditional methods for treatment of chronic facial palsy use a two- stage muscle flap which is time-consuming and burdensome to patients, many of whom are averse to waiting 8 to 12 months to complete the two stages. The one- stage reconstruction method described herein uses a atissimus dorsi free-flap and has demonstrated consistent positive outcomes in clinical assessments.

Avascular Necrosis of the Femoral Head in Patient with Psoriatic Arthritis / 대한류마티스학회지

Psoriatic arthritis and avascular necrosis of the femoral head each are relatively common diseases. However, avascular necrosis of the femoral head in psoriatic arthritisis extremely rare disease and a few cases have been reported to date. It is suggested that the use of steroids or chemotherapeutic agents, hyperuricemia, alcohol abuse, immunologic disorders, coagulopathies are risk factors of the development of avascular necrosis of the femoral head in psoriatic arthritis. This report describes a 58-year-old female patient without any of forementioned risk factors who underwent total hip replacement for femoral head avascular necrosis associated with psoriatic arthritis.

Change of Corneal Astigmatism with Aging in Koreans with Normal Visual Acuity

PURPOSE: To evaluate the distribution and change of corneal astigmatism with aging in persons with normal visual acuity. METHODS: We classified 504 subjects (504 eyes) showing good naked vision at least 1.0 from 3 to 83 years into 15 groups with 5 year interval and analyzed corneal astigmatism using refraction and keratometry. RESULTS: With-the-rule astigmatism (WTR) was shown in 98.5% between 3 and 25 years and progressively decreased with aging. In 61 to 65 years' group WTR was 34.1% and against-the-rule astigmatism (ATR) was 36.4%. After then ATR was more predominant. Mean corneal astigmatism was about 1 diopter under 20 years and progressively decreased to 0.5 D at 60 years with aging. CONCLUSIONS: 84.7% of persons with normal visual acuity have corneal astigmatism. WTR was predominant in the youth but progressively decreased with aging to equal balance with ATR in the mid sixties. After then corneal astigmatism would be inclined to against-the-rule. The amount of corneal astigmatism was decreased from about an 1 diopter in twenties to 0.5 diopter in sixties.