- Normal High HbA1c a Risk Factor for Abnormal Pain Threshold in the Japanese Population. [Journal Article]Front Endocrinol (Lausanne) 2019; 10:651FE
- Purpose: Small fiber dysfunction is common in subjects with diabetic polyneuropathy (DPN). It is unsettled, however, whether marginal glucose intolerance is implicated in the onset and progression of small fiber dysfunction. Herein, we explored the relationship between glycated hemoglobin levels (HbA1c) and pain sensation in the Japanese population. Methods: A population-based study of 894 indi…
Purpose: Small fiber dysfunction is common in subjects with diabetic polyneuropathy (DPN). It is unsettled, however, whether marginal glucose intolerance is implicated in the onset and progression of small fiber dysfunction. Herein, we explored the relationship between glycated hemoglobin levels (HbA1c) and pain sensation in the Japanese population. Methods: A population-based study of 894 individuals (352 men, 542 women; average age 53.8 ± 0.5 years) and 55 subjects with impaired fasting glucose (IFG) in the 2017 Iwaki project were enrolled in this study. Individuals with diabetes were excluded. Relationships between pain threshold for intraepidermal electrical stimulation (P-IES) and parameters associated with metabolic syndrome were examined. Results: P-IES was elevated with increasing of age in women but not in men. Average P-IES (mA) was increased in IFG subjects (n = 55, 0.20 ± 0.03) compared with normoglycemic/non-IFG individuals (n = 894, 0.15 ± 0.11) (p < 0.01). It was comparable between IFG and a group of normal high HbA1c (5.9-6.4%). Univariate linear regression analyses showed no influence of sex, triglyceride, or cholesterol on the value of P-IES. In contrast, there were significant correlations between P-IES and serum HbA1c level (β = 0.120, p < 0.001) Adjustments for the multiple clinical measurements confirmed positive correlation of P-IES with HbA1c (β = 0.077, p = 0.046). Conclusion: Individuals with normal high HbA1c exhibited an elevated P-IES in a healthy Japanese population which may be useful for the screening of subclinical DPN.
- Bowen's disease on the palm: A case report. [Case Reports]World J Clin Cases 2019; 7(18):2910-2915WJ
- CONCLUSIONS: For all atypical palmar lesions, early dermoscopy and/or skin biopsy are needed to avoid missed diagnosis or misdiagnosis.
- Hyperglycemia Suppresses Age-Related Increases in Corneal Peripheral Sensory Nerves in Wistar Bon Kobori (WBN/Kob) Rats. [Journal Article]Invest Ophthalmol Vis Sci 2019; 60(13):4151-4158IO
- CONCLUSIONS: In WBN/Kob rats, hyperglycemia suppresses an age-related increase in peripheral sensory corneal nerve density; therefore, corneal sensory nerves may be important morphological markers of diabetic peripheral sensory neuropathy.
- Tissue-Clearing Technique and Cutaneous Nerve Biopsies: Quantification of the Intraepidermal Nerve-Fiber Density Using Active Clarity Technique-Pressure Related Efficient and Stable Transfer of Macromolecules Into Organs. [Journal Article]J Clin Neurol 2019; 15(4):537-544JC
- CONCLUSIONS: This study has shown that a tissue-clearing method provided not only rapid and highly reproducible three-dimensional images of cutaneous nerve fibers but also yielded reliable quantitative IENFD data. Quantification of the IENFD using a tissue-clearing and labeling technique is a promising way to improve conventional cutaneous nerve biopsies.
- Pharmacological interventions targeting Wnt/β-catenin signaling pathway attenuate paclitaxel-induced peripheral neuropathy. [Journal Article]Eur J Pharmacol 2019; 864:172714EJ
- Chemotherapy-induced peripheral neuropathy (CIPN) is a disabling pain condition which occurs as a consequence of cancer chemotherapy with anti-cancer agents like paclitaxel, oxaliplatin, etc. Despite immense research in the pathological pathways involved in CIPN, treatment options still remain limited. Recently, pathological involvement of Wnt signaling has been investigated in various neuropathi…
Chemotherapy-induced peripheral neuropathy (CIPN) is a disabling pain condition which occurs as a consequence of cancer chemotherapy with anti-cancer agents like paclitaxel, oxaliplatin, etc. Despite immense research in the pathological pathways involved in CIPN, treatment options still remain limited. Recently, pathological involvement of Wnt signaling has been investigated in various neuropathic pain models, however there are no reports as yet on the role of Wnt signaling in CIPN. In the present study, we have investigated the neuroprotective effects of Wnt signaling inhibitors namely LGK974 (Porcupine inhibitor), NSC668036 (Disheveled inhibitor) and PNU76454 (β-catenin inhibitor) in paclitaxel-induced neuropathic pain. Paclitaxel (2 mg/kg, i. p.) was administered to male Sprague Dawley rats on four alternate days. After 21 days, paclitaxel-treated rats showed reduced behavioral pain thresholds (cold allodynia, heat & mechanical hyperalgesia) and nerve functions (nerve conduction velocity and nerve blood flow). Moreover, Wnt signaling proteins (Wnt3a, β-catenin, c-myc and Dvl1), inflammatory marker (matrix metalloproteinase 2) and endoplasmic reticulum stress marker (GRP78) were found to be upregulated in the sciatic nerves of paclitaxel-treated rats accompanied with loss of intraepidermal nerve fiber density as compared to the control rats. Intrathecal administration of Wnt inhibitors (each at dose of 10 and 30 μM) for three consecutive days to paclitaxel-treated rats, significantly improved behavioral pain thresholds and nerve functional parameters by inhibition of Wnt signaling, inflammation, endoplasmic reticulum stress and improvement of intraepidermal nerve fiber density. All these results suggested the neuroprotective potential of Wnt signaling inhibitors in CIPN.
- Letter to the Editor: Reduced intraepidermal nerve fiber density after a sustained increase in insular glutamate: a proof-of-concept study examining the pathogenesis of small fiber pathology in fibromyalgia. [Journal Article]Pain Rep 2019 May-Jun; 4(3):e733PR
- Functional and histological improvements of small nerve neuropathy after high-concentration capsaicin patch application: A case study. [Case Reports]Pain Rep 2019 Jul-Aug; 4(4):e761PR
- CONCLUSIONS: This case report shows the correlation between clinical improvement, electrochemical skin conductance normalization, and intraepidermal nerve fiber density improvement after a high-dose capsaicin patch in a patient with small fiber neuropathy.
- Modern view on epidermal dysplasia carcinogenesis. [Journal Article]Exp Oncol 2019; 41(3):216-223EO
- CONCLUSIONS: Our work has supplemented modern vision of genetic component in pathogenetic mechanism of the development of epidermal dysplasia of the skin. Thus, the association of L-myc (3109TT) with the development of malignant skin lesions of different invasiveness and the modifying effect of TNF-α (G308A) and TP53 (G13494A) gene variants on pathological transformation in the focus of EDS depending on the level of epithelial dysplasia was revealed.
- High Risk of Proximal and Local Neoplasms in 2206 Patients With Anogenital Extramammary Paget's Disease. [Journal Article]Dis Colon Rectum 2019; 62(11):1283-1293DC
- CONCLUSIONS: The registry did not record surveillance schedule, provider specialty, or nonprocedural therapies for extramammary Paget's disease.In the largest published cohort of patients with extramammary Paget's disease, patients with anal Paget's had a much higher risk of both proximal and local neoplasms as compared with patients with genital Paget's. Patients with anal Paget's also experienced worse survival as compared with those with purely genital Paget's. See Video Abstract at http://links.lww.com/DCR/B20. ALTO RIESGO DE NEOPLASIAS PROXIMALES Y LOCALES EN 2206 PACIENTES CON ENFERMEDAD DE PAGET EXTRAMAMARIA ANOGENITAL:: La enfermedad de Paget extramamaria es un adenocarcinoma intraepidérmico poco frecuente con implicaciones clínicas poco definidas.Estimar el riesgo de segundas neoplasias primarias en pacientes con enfermedad de Paget extramamaria.Análisis retrospectivo del Registro de Vigilancia, Epidemiología y Resultados Finales (1973-2014).Registros de base poblacional en cáncer de los Estados Unidos.Pacientes que fueron diagnosticados con enfermedad de Paget anogenital.Riesgo de desarrollo un cáncer primario adicional.Se identificaron 108 pacientes con Paget anal, 421 pacientes con Paget genital masculino (escroto o pene) y 1677 pacientes con Paget genital femenino (vagina o vulva). Tiempo mediano de seguimiento fue de 5,9 años. El riesgo de desarrollar adenocarcinoma colorrectal fue del 18,5% para los pacientes con Paget anal. El ochenta por ciento de los diagnósticos de adenocarcinoma colorrectal fueron sincrónicos (dentro de los 2 meses) a los diagnósticos de Paget anal, mientras que los tumores metacrónicos ocurrieron en un tiempo promedio de 2,4 años. De los pacientes con Paget anal, el 8.3% desarrolló un adenocarcinoma anal o cáncer de células no pequeñas. En los pacientes masculinos con Paget genital, el riesgo de malignidad genitourinaria proximal fue del 9,7%, el adenocarcinoma escrotal o testicular fue del 0,4% y el carcinoma escamoso del pene o escroto fue del 1,7%. En pacientes femeninas con Paget genital, el riesgo de malignidad genitourinaria proximal fue de 3.0%, el adenocarcinoma vaginal o vulvar fue de 1.4% y la neoplasia escamosa vaginal o vulvar fue de 1.0%. La supervivencia general a cinco años fue del 59.7%, 73.5% y 80.7% en pacientes con anal, genital masculino y genital femenino, respectivamente (p <0.001).El registro no señalo el cronograma de vigilancia, la especialidad del proveedor o las terapias sin procedimiento para la enfermedad de Paget extramamaria.En la cohorte más grande publicada de pacientes con enfermedad de Paget extramamaria, los pacientes con Paget anal demostraron un riesgo mucho mayor de neoplasias proximales y locales en comparación con los pacientes con Paget genital. Los pacientes con Paget anal además demostraron una peor supervivencia en comparación con aquellos con Paget aislada genital. Vea el Resumen del Video en http://links.lww.com/DCR/B20.
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- Effect of diabetes type on long-term outcome of epidermal axon regeneration. [Journal Article]Ann Clin Transl Neurol 2019; 6(10):2088-2096AC
- CONCLUSIONS: Among diabetic patients, nerve injury recovery is likely to take significantly longer than in healthy individuals, and remains incomplete, particularly among type 2 patients. This may partially explain the progression of neuropathy among diabetic patients: damage accumulates because nerve recovery is slowed and incomplete. Furthermore, these findings support caution when recommending certain procedures, such as carpal tunnel repair, to patients with progressed diabetic disease.