Diagnosis and treatment of nail melanoma: a review of the clinicopathologic, dermoscopic, and genetic characteristics.

Nail melanoma (NM) is an important differential diagnosis in patients with longitudinal melanonychia. However, diagnosis is often challenging as it is difficult to differentiate from other pigmented nail disorders. The main challenge for diagnosis is obtaining adequate nail matrix biopsy specimens for histopathological assessment. Furthermore, the histopathological changes in the early stages of NM are subtle and contribute to a delay in diagnosis and care. Therefore, the integration of clinical and histopathological analyses is essential. Clinical and dermoscopic features, such as a broadened width of asymmetric bands in an irregular pattern, with multicolour pigmentation, periungual pigmentation, and continuous growth, are features that support the diagnosis of NM. The essential histological features that must be assessed are cellular morphology, architectural features, melanocyte density, and inflammatory changes. The reported mutations in NMs were BRAF (0-43%), NRAS (0-31%), KIT (0-50%), NF1 (0-50%), and GNAQ (0-25%). Surgery is the primary treatment for NM. The recommended treatment for in situ or minimally invasive NM is functional surgery, but cases with suspected bone invasion should be treated with amputation. Targeted therapy and immunotherapy are indicated for advanced stages of NM. This review summarizes the updated guidelines for the diagnosis and treatment of NM.

Unstable Non-isthmic Spondylolisthesis Following Unilateral Biportal Endoscopy Assisted Unilateral Laminotomy for Bilateral Decompression: A Case Report.

Lumbar decompressive laminectomy is a standard treatment for degenerative lumbar spinal stenosis, but in some cases, can lead to iatrogenic spondylolysis and delayed segmental instability. Iatrogenic spondylolysis occurs in most cases in pars interarticularis, but rare cases have also been reported, pediculolysis in pedicle and laminolysis in lamina. Minimally invasive spine surgery (MIS) is known to have a low risk of developing these iatrogenic spondylolyses, and unilateral biportal endoscopy is the MIS that has been drawing attention. We present a case of a 72-year-old female who was diagnosed with L4-5 unstable non-isthmic spondylolisthesis and severe right central disc extrusion 10 weeks after UBE assisted unilateral laminotomy for bilateral decompression (ULBD) at the consecutive segments of L3-4 and L4-5. Pre-operative imaging studies revealed severe central stenosis without spondylolisthesis at L3-L4 and L4-L5 along with L4-L5 facet tropism. She was managed by anterior lumbar interbody fusion and cement augmented pedicle screw fixation, which resulted in the complete resolution of her clinical and neurologic symptoms.

Author Correction: Waist circumference and the risk of lumbar and femur fractures: a nationwide population-based cohort study.

Correction to: European Review for Medical and Pharmacological Sciences 2021; 25 (3): 1198-1205-DOI: 10.26355/eurrev_202102_24822-PMID: 33629289, published online 15 February, 2021. After publication, the authors requested to correct Table I and some minor errors in the text. There are amendments to this paper. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/24822.

Waist circumference and the risk of lumbar and femur fractures: a nationwide population-based cohort study.

Although obesity is known to have an influence on fracture, the relationship between lumbar and femur fractures and weight or waist circumference is controversial. We investigated the incidence of fracture with regards to waist circumference using the customised database of the Korean National Health Insurance Service (NHIS). Among 8,922,940 adults who participated at least twice in the NHIS National Health Check-up Program in South Korea between 2009 and 2011, 1,556,751 subjects (780,074 men and 776,677 women) were extracted. Over a mean follow-up of 6.5 years, multivariate-adjusted logistic regression analysis demonstrated that higher waist circumference was associated with an increased risk of femur fractures in both males and females. Moreover, the incidence of lumbar fractures was also positively associated with an increased waist circumference in males and females. An increased waist circumference showed a positive linear relationship with the risk of lumbar and femur fractures in both males and females.

Visit-to-visit changes in fasting blood sugar and the risk for cardiovascular disease and mortality in the Korean population: a nationwide population-based cohort study.

OBJECTIVE: The importance of continuous monitoring of fasting blood sugar (FBS) levels of diabetic patients has been established. MATERIALS AND METHODS: An observational prospective study was conducted. Our analysis included 1,700,796 individuals from the nationwide South Korean National Health Insurance System cohort. FBS variability was measured by standard deviation (SD). RESULTS: Kaplan-Meier curves demonstrated elevated disease probability in the higher FBS fluctuation group compared with the lower FBS fluctuation group. After adjusting for confounding variables, Cox proportional hazards analysis showed that the hazard ratios of 411 individuals in the highest quartile of SD variation of FBS were 1.77 (95% confidence interval 1.37-2.28, p<0.001) compared with the lowest quartile of SD variation of FBS. The impact of FBS fluctuation on the risk of cardiovascular diseases (CVDs), cerebrovascular diseases, CVD mortality and all-cause mortality in the highest quartiles of diabetic and non-diabetic individuals was statistically significant. CONCLUSIONS: Visit-to-visit FBS variability has prognostic value for predicting micro- and macrovascular disease, cardiovascular mortality, and all-cause mortality.

The severity of periodontitis and metabolic syndrome in Korean population: The Dong-gu study.

OBJECTIVES: We assessed the association between periodontal disease status and metabolic syndrome (MetS) and its individual components in Korean adults over 50 years old. MATERIAL AND METHODS: In the Dong-gu study, 5078 men and women aged over 50 years were included. They underwent a questionnaire survey, physical assessment, biochemical assessment and periodontal assessment. The percentages of sites with periodontal probing depth ≥4 mm, and clinical attachment loss ≥4 mm were recorded for each participant. Periodontal disease was also classified by the Centers for Disease Control and Prevention/American Academy of Periodontology definition of periodontitis and the American Academy of Periodontology definition (1999). MetS was defined by the 2009 guidelines of the International Diabetes Federation. This study used multivariate negative binominal regression analysis to assess the association between the severity of periodontitis and MetS, after age, smoking habits, alcohol consumption and physical activity related factors were adjusted for. RESULTS: Prevalence of MetS was 32.3%, 36.2% and 45.9% among men with no or mild, moderate and severe periodontitis, respectively. The severity of periodontitis was positively associated with the prevalent MetS in men but not in women. In men, severe periodontitis showed a higher risk of MetS than those with no or mild periodontitis (relative risk 1.43, 95% confidence interval 1.17-1.73) after adjusting for confounders. Periodontal probing depth was positively associated with the prevalence of MetS in both genders. In the analysis separated by individual MetS components, periodontitis severity was positively associated with hypertriglyceridemia and low high-density lipoprotein cholesterol in men, while positively associated with low high-density lipoprotein cholesterol and abdominal obesity in women. CONCLUSION: Increasing the severity of periodontitis was associated with the risk of prevalent MetS in Korean adults. This result confirmed that periodontal inflammation might be a contributive factor of MetS.

Identification of lactoferrin and glutamate receptor-interacting protein 1 in bovine cervical mucus: A putative marker for oestrous detection.

Accurate detection of oestrus is important for artificial insemination. The aim of this study was to identify oestrous-specific bovine cervical mucus proteins that could be used to determine the optimal time for artificial insemination. Non-oestrous and controlled internal drug release (CIDR)-induced oestrous-stage mucus proteins were purified and subjected to surface-enhanced laser desorption/ionization time-of-flight mass spectrometry, sodium dodecyl sulphate polyacrylamide gel electrophoresis and MALDI-TOF/TOF. Among differentially expressed proteins, lactoferrin (LF) and glutamate receptor-interacting protein 1 (GRIP1) showed a twofold increase during the CIDR-induced oestrous stage compared to the levels in non-oestrous stage in bovine cervical mucus. The RT-PCR, Western blotting and immunohistochemistry results showed that LF and GRIP1 expression was significantly increased during the oestrous stage in the uterus. This study demonstrated that bovine LF and GRIP1 exist during the oestrous stage, but not during the non-oestrous stage, suggesting that cervical mucus LF and GRIP1 are useful oestrous detection markers in cattle.

Reduction of magnetic damping and isotropic coercivity and increase of saturation magnetization in Rh-incorporated CoIr system.

Replacing Ir with Rh in a CoIr system possessing negative uniaxial magnetocrystalline anisotropy (K u ) substantially reduces its magnetic damping and coercivity by more than half while retaining its high negative K u . Moreover, a higher saturation magnetization (M s ) and more isotropic coercivity are achieved. Such material development makes it particularly suitable for use as the soft underlayer (SUL) of magnetic recording media for reducing noise, and as the oscillation layer of a spin-torque oscillator (STO) for achieving higher oscillation frequency, larger AC magnetic field and lower driving current, which can be readily integrated with the current recording head for microwave-assisted magnetic recording. Finally, we recommend a composite free layer by coupling CoIr with a spin polarizer (Co or Co/Cu/Co) for the enhancement of the spin-polarization rate and, therefore, the improvement of STO efficiency. These could pave the way for CoIr-based materials to be implemented in devices requiring a negative Ku with low damping and high 'softness', such as oscillators.

Differential characteristics of pediatric sinusitis in patients who underwent endoscopic sinus surgery: children vs. adolescents.

OBJECTIVES: We hypothesised that paediatric chronic sinusitis patients might have various clinical characteristics, depending on age, compared symptoms, physical findings and clinical features in younger children and older adolescent patients who underwent endoscopic sinus surgery. DESIGN: A retrospective review of medical records. SETTING: A total of 195 paediatric patients who underwent Endoscopic sinus surgery were enrolled and medical records were reviewed. PARTICIPANTS: The subjects were divided into children (age < 12 years, n = 70, mean age = 9.6 years) and adolescents (age ≥ 12 years, n = 125, mean age = 14.7 years). MAIN OUTCOME MEASURES: Subjective symptoms, physical findings, CT images and clinical features were compared in children and adolescent groups. RESULTS: Cough and nasal obstruction were more common in adolescents, and sleep disturbance was more common in children. Nasal mucosal injection was more common in adolescents, whereas tonsils were larger in children. Septal deviation was a more common finding in adolescents, and total CT score and serum total IgE levels were higher in children. There was no statistical difference in rate of recurrence after endoscopic sinus surgery. CONCLUSION: The clinical features of paediatric chronic sinusitis differed between the younger and older groups. Symptomatic, anatomical and clinical differences between these two groups suggest that further study of paediatric chronic sinusitis should stratify patients by age to better understand the effects of treatment on each age group.

Surgical management of damaged inferior alveolar nerve caused by endodontic overfilling of calcium hydroxide paste.

AIM: To evaluate the neurosensory outcome of management of damaged inferior alveolar nerves caused by endodontic overfilling and to assess the efficacy of delayed surgical intervention. METHODOLOGY: Nine patients who underwent surgical removal of extruded endodontic material were included. All patients were evaluated for neurosensory function using a set of standardized tests. The outcome of surgical intervention was evaluated through patient interview and quantitative statistical analysis. RESULTS: Surgical procedures included foreign body removal, microsurgical external/internal decompression, excision of neuroma followed by nerve repair, and excision of damaged nerve segment with interpositional nerve graft. Seven of the nine patients had significant improvement according to the follow-up neurosensory assessment. Four patients reported significant improvement, three patients reported mild improvement and two patients reported no appreciable improvement in the Visual Analog Scale (VAS). Two patients who reported no appreciable improvement in VAS also did not achieve FSR. In these patients, calcium hydroxide was spread widely along the IAN and a surgical approach was obtained via sagittal spit osteotomy. The mean time to reach FSR was 222.7 (±41.8) days with a range of 106-397 days. In the early repair group who received surgery within 60 days, three out of five patients achieved FSR in a mean time of 198.0 (±76.2) days. The mean time to FSR in all four subjects who received surgical attention over 60 days after injury was 241.3 (±139.8) days with a range of 106-397 days. As all four cases in the late repair group with limited amount of nerve injury achieved FSR, only 3 of 5 early repair cases with wide-spread injury achieved a similar outcome. CONCLUSION: The results of this case series confirmed the notion that surgical management of the inferior alveolar nerve is effective in the treatment of nerve injuries caused by endodontic extrusion of calcium hydroxide paste. Delayed surgical repair of the inferior alveolar nerve can be indicated and helpful for the neurosensory recovery of damaged IAN, however, the surgical management was less effective in case of widespread nerve injuries.

Comparison of calcium alginate and carboxymethyl cellulose for nasal packing after endoscopic sinus surgery: a prospective, randomised, controlled single-blinded trial.

OBJECTIVES: Calcium alginate is a biodegradable gel-transforming agent widely used for nasal packing. It can reduce pain and improve comfort. However, few randomised controlled trials have compared the efficacy of calcium alginate nasal packing with that of other biodegradable gel-transforming materials. DESIGN: Prospective, randomised, single-blinded controlled study. SETTING: Yonsei University Severance Hospital, a tertiary academic medical centre. PARTICIPANTS: Twenty-seven patients (54 nostrils) with chronic rhinosinusitis who were scheduled for bilateral endoscopic sinus surgery were enrolled. After surgery, one nostril was packed with calcium alginate and the other with carboxymethyl cellulose. Only patients with an intersinus chronic rhinosinusitis severity score difference of ≤1 were included. MAIN OUTCOME MEASURES: Visual analogue scale (VAS) scores for postoperative pain, discomfort from nasal discharge and pain during packing removal were analysed. Two independent rhinologists who were blinded to the assessments separately scored adhesions, oedema and infection by endoscopic digital photography at 1, 4 and 8 weeks postoperatively. RESULTS: There were no significant differences in VAS scores for postoperative pain, discomfort from nasal discharge or pain during packing removal between calcium alginate packings and carboxymethyl cellulose packings. Inter-rater variability of adhesion, oedema and infection scores was acceptable. Adhesion severity and oedema scores at 4 weeks were significantly lower with calcium alginate packing than with carboxymethyl cellulose. Infection severity scores also tended to be lower with calcium alginate than with carboxymethyl cellulose, but the difference was not significant. CONCLUSIONS: Calcium alginate nasal packing is associated with reduced severity of oedema and adhesions after endoscopic sinus surgery.

Biomechanical properties of titanium elastic nail applied to a cadaveric clavicle model.

BACKGROUND: The goal of this study was to examine biomechanical properties of titanium elastic nail fixation method that was applied to cadaveric clavicles with different thicknesses and lengths. METHODS: To test stiffness and failure load of clavicle with titanium elastic nail fixation, 12 pairs of clavicles were obtained. A short oblique fracture line (AO/OTA classification: 15-B1.2) was created at midpoint of the cadaveric bones. They were divided into four groups according to the nails with different thickness and length/diameter ratios. The fixated bones were situated on a jig that allows 3-point bending to measure stiffness and load failure. RESULTS: The stiffness was measured to be mean 3.49 ± 1.49 N/mm in group 1. The stiffness for group 2 was mean 10.41 ± 2.18 N/mm, and for groups 3 and 4, the stiffness was mean 11.89 ± 2.99 N/mm and mean 24.44 ± 4.86 N/mm, respectively. When analyzed with statistics, group 1 had significant differences from groups 2 (P < 0.006), 3 (P < 0.001), and 4 (P < 0.000), and group 4 also had statistical significances from rest of the groups (P < 0.000). CONCLUSIONS: For 2.5 mm titanium elastic nail, it is necessary to make fixation with a titanium elastic nail that is longer than 3 diameter lengths, and length that is longer than and equal to 3 diameter length titanium elastic nail was required for 3.5 mm titanium elastic nail to provide appropriate stiffness for firm fixation. Also, variances in both thickness and length have shown a similar effect. STUDY DESIGN: Cadaveric study.

Manipulation of a quasi-natural cell block for high-efficiency transplantation of adherent somatic cells

Recent advances have raised hope that transplantation of adherent somatic cells could provide dramatic new therapies for various diseases. However, current methods for transplanting adherent somatic cells are not efficient enough for therapeutic applications. Here, we report the development of a novel method to generate quasi-natural cell blocks for high-efficiency transplantation of adherent somatic cells. The blocks were created by providing a unique environment in which cultured cells generated their own extracellular matrix. Initially, stromal cells isolated from mice were expanded in vitro in liquid cell culture medium followed by transferring the cells into a hydrogel shell. After incubation for 1 day with mechanical agitation, the encapsulated cell mass was perforated with a thin needle and then incubated for an additional 6 days to form a quasi-natural cell block. Allograft transplantation of the cell block into C57BL/6 mice resulted in perfect adaptation of the allograft and complete integration into the tissue of the recipient. This method could be widely applied for repairing damaged cells or tissues, stem cell transplantation, ex vivo gene therapy, or plastic surgery.

Manipulation of a quasi-natural cell block for high-efficiency transplantation of adherent somatic cells.

Recent advances have raised hope that transplantation of adherent somatic cells could provide dramatic new therapies for various diseases. However, current methods for transplanting adherent somatic cells are not efficient enough for therapeutic applications. Here, we report the development of a novel method to generate quasi-natural cell blocks for high-efficiency transplantation of adherent somatic cells. The blocks were created by providing a unique environment in which cultured cells generated their own extracellular matrix. Initially, stromal cells isolated from mice were expanded in vitro in liquid cell culture medium followed by transferring the cells into a hydrogel shell. After incubation for 1 day with mechanical agitation, the encapsulated cell mass was perforated with a thin needle and then incubated for an additional 6 days to form a quasi-natural cell block. Allograft transplantation of the cell block into C57BL/6 mice resulted in perfect adaptation of the allograft and complete integration into the tissue of the recipient. This method could be widely applied for repairing damaged cells or tissues, stem cell transplantation, ex vivo gene therapy, or plastic surgery.

PHF2 histone demethylase acts as a tumor suppressor in association with p53 in cancer.

Plant homeodomain finger 2 (PHF2) has a role in epigenetic regulation of gene expression by demethylating H3K9-Me2. Several genome-wide studies have demonstrated that the chromosomal region including the PHF2 gene is often deleted in some cancers including colorectal cancer, and this finding encouraged us to investigate the tumor suppressive role of PHF2. As p53 is a critical tumor suppressor in colon cancer, we tested the possibility that PHF2 is an epigenetic regulator of p53. PHF2 was associated with p53, and thereby, promoted p53-driven gene expression in cancer cells under genotoxic stress. PHF2 converted the chromatin that is favorable for transcription by demethylating the repressive H3K9-Me2 mark. In an HCT116 xenograft model, PHF2 was found to be required for the anticancer effects of oxaliplatin and doxorubicin. In PHF2-deficient xenografts, p53 expression was profoundly induced by both drugs, but its downstream product p21 was not, suggesting that p53 cannot be activated in the absence of PHF2. To find clinical evidence about the role of PHF2, we analyzed the expressions of PHF2, p53 and p21 in human colon cancer tissues and adjacent normal tissues from patients. PHF2 was downregulated in cancer tissues and PHF2 correlated with p21 in cancers expressing functional p53. Colon and stomach cancer tissue arrays showed a positive correlation between PHF2 and p21 expressions. Informatics analyses using the Oncomine database also supported our notion that PHF2 is downregulated in colon and stomach cancers. On the basis of these findings, we propose that PHF2 acts as a tumor suppressor in association with p53 in cancer development and ensures p53-mediated cell death in response to chemotherapy.

Nitric oxide induces apoptosis in human gingival fibroblast through mitochondria-dependent pathway and JNK activation.

AIM: To investigate the molecular mechanisms of nitric oxide (NO)-induced cytotoxic effect in human gingival fibroblast (HGF) cells. METHODOLOGY: After sodium nitroprusside (SNP), as NO donor, was treated to HGF, viability was measured by MTT assay and apoptosis was determined by TUNEL and DNA fragmentation assay. Mitochondrial membrane potential was detected using confocal microscopy, and caspase activity assay was measured by spectrophotometer. Mitogen-activated protein kinases (MAPK) activation, Bax/Bcl-2 ratio and cytochrome c release were analysed by Western blot analyses. Cells were exposed to MAPK inhibitors (U0126, SB203580 and SP600125) before SNP treatment to investigate the effects of MAPK kinases on the NO-induced apoptosis in HGF. Statistical analysis was performed using one-way analysis of variance with the Student-Newman-Keuls post hoc test for multiple group comparison. RESULTS: Apoptosis was significantly increased (P = 0.011 and 0.0004, respectively) in the presence of SNP (1 and 3 mmol L(-1) ) after 12 h in HGF. However, 1H-[1,2,4] oxadiatolo [4, 3-a] cluinoxaline-1-one (ODQ), a soluble guanylate cyclase inhibitor, did not block the decrement of cell viability by NO. SNP treatment induced the loss of mitochondrial membrane potential, release of cytochrome c, increased Bax/Bcl-2 ratio and activation of caspases in HGF. Also, SNP treatment increased phosphorylation of MAPKinases and c-Jun N-terminal kinase (JNK) inhibitor (5 and 10 µmol L(-1) ) rescued cell viability decreased by SNP in HGF (P = 0.024 and 0.0149, respectively). CONCLUSION: Nitric oxide induced apoptosis in human gingival fibroblast through the mitochondria-mediated pathway by regulation of Bcl-2 family and JNK activation.

NMDA receptors and L-type voltage-gated Ca²âº channels mediate the expression of bidirectional homeostatic intrinsic plasticity in cultured hippocampal neurons.

Homeostatic plasticity is engaged when neurons need to stabilize their synaptic strength and excitability in response to acute or prolonged destabilizing changes in global activity. Compared to the extensive studies investigating the molecular mechanisms for homeostatic synaptic plasticity, the mechanism underlying homeostatic intrinsic plasticity is largely unknown. Through whole-cell patch-clamp recording in low-density cultures of dissociated hippocampal neurons, we demonstrate here that prolonged activity blockade induced by the sodium channel blocker tetrodotoxin (TTX) leads to increased action potential firing rates. Conversely, prolonged activity enhancement induced by the A-type gamma-aminobutyric acid receptor antagonist bicuculline (BC) results in decreased firing rates. Prolonged activity enhancement also enhanced potassium (K(+)) current through Kv1 channels, suggesting that changes in K(+) current, in part, mediate stabilization of hippocampal neuronal excitability upon prolonged activity elevation. In contrast to the previous reports showing that L-type voltage-gated calcium (Ca(2+)) channels solely mediate homeostatic regulation of excitatory synaptic strength (Ibata et al., 2008; Goold and Nicoll, 2010), inhibition of N-Methyl-d-aspartate (NMDA) receptors alone mimics the elevation in firing frequency driven by prolonged TTX application, while the decrease in firing rates induced by prolonged BC treatment involves the activity of NMDA receptors and L-type voltage-gated Ca(2+) channels. These results collectively provide strong evidence that alterations in Ca(2+) influx through NMDA receptors and L-type voltage-gated Ca(2+) channels mediate homeostatic intrinsic plasticity in hippocampal neurons in response to prolonged activity changes.

Characterization of GFRα-1-positive and GFRα-1-negative spermatogonia in neonatal pig testis.

Type A spermatogonia, including spermatogonial stem cells, are primary cells that maintain spermatogenesis and produce spermatozoa. Many spermatogonial markers have been reported in rodents. However, few markers have been identified in pig spermatogonia. Despite the lack of information, it is necessary to separate pure spermatogonial cells from whole testicular cells to understand the mechanism of spermatogenic meiosis and to establish spermatogonial stem cells for further biotechnological studies. The purpose of this study was to identify glial cell-derived neurotrophic factor receptor alpha-1 (GFRα-1) as a surface marker for early spermatogonia in neonatal pig testes. Histological analysis of 3-day-old pig testes revealed that type A spermatogonia, which lack heterochromatin, could be distinguished in neonatal pig testes. Immunohistochemistry of neonatal pig testes with GFRα-1 antibody identified that some of the spermatogonial cells expressed GFRα-1 on the cell membrane. Co-immunostaining with both GFRα-1 and protein gene product 9.5 (PGP 9.5) detected PGP 9.5 in all spermatogonia of neonatal pig testes, whereas GFRα-1 was not detected on the surface of some PGP 9.5-positive cells, indicating that some of the spermatogonial cells were PGP 9.5 positive and GFRα-1 negative. After immunomagnetic cell sorting using a GFRα-1 antibody, both GFRα-1-positive and GFRα-1-negative cells expressed PGP 9.5. Identifying the differential mRNA expression of both GFRα-1-positive and GFRα-1-negative cells using reverse transcription-polymerase chain reaction analysis revealed the expression of promyelocytic leukaemia zinc finger, octamer-binding protein 4 and homeobox transcription factor in both cell types. These results suggest that GFRα-1-positive and GFRα-1-negative spermatogonia exist in PGP 9.5-positive spermatogonia during the early stage of pig testes spermatogenesis, and that GFRα-1 can be used for sorting PGP 9.5-expressing spermatogonia.

Antinociceptive curcuminoid, KMS4034, effects on inflammatory and neuropathic pain likely via modulating TRPV1 in mice.

BACKGROUND: Curcumin, the active ingredient of turmeric (Curcuma longa), has a wide range of beneficial effects including anti-inflammation and analgesia. However, poor bioavailability of curcumin hinders its clinical application. To overcome this limitation, we modified the structure of curcumin and synthesized new derivatives with favourable pharmacokinetic profiles. Recently, curcumin has been shown to have an antagonizing effect on transient receptor potential vanilloid type 1 (TRPV1) ion channels. We investigated the antinociceptive activity of KMS4034 which had the most favourable pharmacokinetics among the tested curcumin derivatives. METHODS: To evaluate the mechanism of the antinociceptive effects of KMS4034, capsaicin (I(CAP))- and heat (I(heat))-induced currents in TRPV1 expressing HEK293 cells were observed after the application of KMS4034. Nociceptive behavioural measurement using the hot-plate test, formalin test, and chronic constriction injury (CCI) model were evaluated in mice. Also, calcitonin gene-related peptide (CGRP) was stained immunohistochemically in the L4/5 dorsal horns in mice with neuropathic pain. RESULTS: I(CAP) (P<0.01) and I(heat) (P<0.05) of TRPV1 were significantly blocked by 10 µM KMS4034. Behaviourally, noticeable antinociceptive effects after 10 mg kg(-1) of KMS4034 treatment were observed in the first (P<0.05) and second phases (P<0.05) of the formalin and hot-plate tests. The mechanical threshold of CCI mice treated with 10 mg kg(-1) KMS4034 was significantly increased compared with control. Immunohistochemical CGRP expression was decreased in the lamina I-II of the lumbar dorsal horns in KMS4034-treated CCI mice compared with the control (P<0.05). CONCLUSIONS: KMS4034 may be an effective analgesic for various pain conditions.

Stage-specific embryonic antigen-1 expression by undifferentiated spermatogonia in the prepubertal boar testis.

The objective of this study was to use fluorescence-activated cell sorting (FACS) and spermatogonial stem cell (SSC) xenotransplantation to identify cell surface markers of putative porcine SSC. Analysis of porcine testis cells enriched for spermatogonia using FACS indicated that nearly half of stage-specific embryonic antigen-1 (SSEA-1) expressing testis cells expressed the undifferentiated spermatogonia marker protein gene product 9.5 (PGP 9.5) whereas significantly fewer (P < 0.05) cells selected for thymus cell antigen-1 (Thy-1), also known as cluster of differentiation 90 (CD90), cluster of differentiation 9 (CD9), or other SSC markers expressed PGP 9.5. Immunocytochemical analysis indicated that promyelocytic leukemia zinc finger (PLZF) protein and germ cell lineage marker VASA homolog (VASA), also known as DEAD box protein 4 (DDX4), were expressed by SSEA-1 expressing germ cells. Spermatogonial stem cell xenotransplantation of testis cell populations enriched for cells expressing SSEA-1 generated significantly (P < 0.05; greater than 15-fold) more colonies of donor derived germ cells than unselected testis cells. In conclusion, these data indicate that SSC markers identified in rodents are likely not entirely conserved in pigs and that SSEA-1 is a marker for porcine undifferentiated spermatogonia including SSC in prepubertal boars and its expression may serve as a target for the further study of porcine germ cells.