Intralymphatic Histiocytosis Associated with Osteoarthritis: A Case Report

Intralymphatic histiocytosis (ILH) is a rare cutaneous condition with uncertain pathogenesis. It is characterized by dilated lymphatic vessels that contain histiocytes within their lumina. Although the etiology of ILH remains unknown, it has been associated with various inflammatory and neoplastic diseases, such as rheumatoid arthritis (RA), reaction to metal joint implants and Merkel cell carcinoma, breast cancer and colon cancer. An 83-year-old female presented with an erythematous patch on the left forearm that had appeared six months previous. She had suffered from osteoarthritis (OA) and the cutaneous lesion was located in the vicinity of the affected joint. Skin biopsy from the lesion showed dilated dermal vessels and some ectatic vessels that contained many mononuclear histiocytes. Based on the clinical and histopathological findings, we diagnosed her with ILH with OA. Two sessions of intralesional triamcinolone acetonide injection (5 mg/ml) were administered to treat the skin lesion, which gradually improved over a period of a few months. We here report a rare case of ILH associated with degenerative OA.     

Comparison of Initial Presentation of Pediatric Diabetes Before and During the Coronavirus Disease 2019 Pandemic Era

BackgroundHospital visitation has become challenging during the coronavirus disease 2019 pandemic because of quarantine measures and fear of infection. Consequently, newly diagnosed patients may present with more severe diseases during the pandemic. The present study analyzed the differences in the initial clinical presentations of newly diagnosed patients with type 1 diabetes (T1D) and type 2 diabetes (T2D), comparing pre-pandemic and pandemic periods.MethodsNewly diagnosed patients with T1D or T2D and aged < 18 years during 2018–2020 were included in the study. Data were collected retrospectively from four academic centers in Gyeonggi-do, South Korea. Initial clinical data were compared between the pre-pandemic (2018–2019) and pandemic (2020) periods.ResultsIn the pre-pandemic and pandemic periods, 99 patients (41 T1D and 58 T2D patients) and 84 patients (51 T1D and 33 T2D patients) were identified, respectively. During the pandemic, the proportion of diabetic ketoacidosis (DKA) cases increased compared to the pre-pandemic period (21.2% during 2018–2019 vs. 38.1% in 2020; P = 0.012). In the pre-pandemic and pandemic periods, initial pH was 7.32 ± 0.14 and 7.27 ± 0.15, respectively (P = 0.040), and HbA1c values were 11.18 ± 2.46% and 12.42 ± 2.87%, respectively (P = 0.002). During the pandemic, there was an increased risk of DKA in patients with T1D (odds ratio, 2.42; 95% confidence interval, 1.04–5.62; P = 0.040).ConclusionDuring the pandemic, the proportion of DKA in newly diagnosed patients with T1D increased and clinical parameters showed a deteriorating pattern. Increased awareness of pediatric diabetes, especially DKA, could facilitate visit to the hospital for an early diagnosis; thus, reducing the number of DKA cases during the pandemic era.     

Sodium Glucose Cotransporter-2 Inhibitors as an Add-on Therapy to Metformin Plus Dipeptidyl Peptidase-4 Inhibitor in Patients with Type 2 Diabetes

PurposeTo date, no study has compared the effects of adding sodium glucose cotransporter-2 (SGLT-2) inhibitors to the combination of metformin plus dipeptidyl peptidase-4 (DPP-4) inhibitors to the effects of adding other conventional anti-diabetic drugs (ADDs) to the dual therapy. We aimed to compare the effect of adding SGLT-2 inhibitors with that of adding sulfonylurea (SU) in type 2 diabetes (T2D) patients inadequately controlled with metformin plus DPP-4 inhibitors.Materials and MethodsThis study was designed to evaluate the non-inferiority of SGLT-2 inhibitor to SU as an add-on therapy to the dual combination of metformin plus DPP-4 inhibitors. A total of 292 T2D patients who started SU or SGLT-2 inhibitors as an add-on therapy to metformin plus DPP-4 inhibitors due to uncontrolled hyperglycemia, defined as glycated hemoglobin (HbA1c) ≥7%, were recruited. After propensity score matching, 90 pairs of patients remained, and 12-week changes in HbA1c levels were reviewed to assess glycemic effectiveness. Data from these patients were analyzed retrospectively.ResultsAfter 12 weeks of triple therapy, both groups showed significant changes in HbA1c levels, with a mean of -0.9% in each group. The inter-group difference was 0.01% [95% confidence interval (CI): -0.26–0.27], and the upper limit of the 95% CI was within the limit for non-inferiority (0.40%). There were no inter-group differences in the changes of liver enzyme levels and kidney function.ConclusionAdding SGLT-2 inhibitors is not inferior to adding SU as a third-line ADD to metformin plus DPP-4 inhibitor combination therapy.     

Glycine induces enhancement of bactericidal activity of neutrophils

Severe bacterial infections are frequently accompanied by depressed neutrophil functions. Thus, agents that increase the microbicidal activity of neutrophils could add to a direct antimicrobial therapy. Lysophosphatidylcholine augments neutrophil bactericidal activity via the glycine (Gly)/glycine receptor (GlyR) α2/TRPM2/p38 mitogen-activated protein kinase (MAPK) pathway. However, the direct effect of glycine on neutrophil bactericidal activity was not reported. In this study, the effect of glycine on neutrophil bactericidal activity was examined. Glycine augmented bactericidal activity of human neutrophils (EC₅₀ = 238 μM) in a strychnine (a GlyR antagonist)-sensitive manner. Glycine augmented bacterial clearance in mice, which was also blocked by strychnine (0.4 mg/kg, s.c.). Glycine enhanced NADPH oxidase-mediated reactive oxygen species (ROS) production and TRPM2-mediated [Ca²⁺]_i increase in neutrophils that had taken up E. coli. Glycine augmented Lucifer yellow uptake (fluid-phase pinocytosis) and azurophil granule-phagosome fusion in neutrophils that had taken up E. coli in an SB203580 (a p38 MAPK inhibitor)-sensitive manner. These findings indicate that glycine augments neutrophil microbicidal activity by enhancing azurophil granule-phagosome fusion via the GlyRα2/ROS/calcium/p38 MAPK pathway. We suggest that glycine could be a useful agent for increasing neutrophil bacterial clearance.     

Inhibitory effects of the atypical antipsychotic,clozapine, on voltage-dependent K+ channels in rabbit coronary arterial smooth muscle cells

To investigate the adverse effects of clozapine on cardiovascular ion channels, we examined the inhibitory effect of clozapine on voltage-dependent K⁺ (Kv) channels in rabbit coronary arterial smooth muscle cells. Clozapine-induced inhibition of Kv channels occurred in a concentration-dependent manner with an half-inhibitory concentration value of 7.84 ± 4.86 µM and a Hill coefficient of 0.47 ± 0.06. Clozapine did not shift the steady-state activation or inactivation curves, suggesting that it inhibited Kv channels regardless of gating properties. Application of train pulses (1 and 2 Hz) progressively augmented the clozapine-induced inhibition of Kv channels in the presence of the drug. Furthermore, the recovery time constant from inactivation was increased in the presence of clozapine, suggesting that clozapine-induced inhibition of Kv channels is use (state)-dependent. Pretreatment of a Kv1.5 subtype inhibitor decreased the Kv current amplitudes, but additional application of clozapine did not further inhibit the Kv current. Pretreatment with Kv2.1 or Kv7 subtype inhibitors partially blocked the inhibitory effect of clozapine. Based on these results, we conclude that clozapine inhibits arterial Kv channels in a concentration- and use (state)-dependent manner. Kv1.5 is the major subtype involved in clozapine-induced inhibition of Kv channels, and Kv2.1 and Kv7 subtypes are partially involved.     

糖尿病肾病患者血清Ⅳ型胶原和层粘连蛋白水平的变化及临床价值

目的探讨糖尿病肾病(DN)患者血清中Ⅳ型胶原(C-Ⅳ)和层粘连蛋白(LN)水平的变化及其临床价值。方法用放射免疫法测定81例糖尿病(DM)患者(男48例,女33例)的血清C-Ⅳ和LN含量,分为正常白蛋白尿组36例,微量白蛋白尿组29例和大量白蛋白尿组16例,并以50例健康体检者为对照。用直线相关分析糖尿病患者血清C-Ⅳ、LN与其它临床指标之间的相关性。结果81例DM患者血清C-Ⅳ[(74.6±24.2μg/L]、LN[(137.1±29.5)μg/L]水平明显高于对照组[(45.4±7.9)、(98.6±15.4)μg/L,P<0.01];DM各亚组患者血清C-Ⅳ、LN水平均明显高于对照组(P<0.05,P<0.01);DM各组间血清C-Ⅳ、LN水平随尿白蛋白量的增加而升高,差异有统计学意义(P<0.05,P<0.01)。直线相关分折提示血清LN及C-Ⅳ水平均与BUN、Cr、HbA1C、UAER相关(P<0.05,P<0.01),血清C-Ⅳ、LN水平与FBG无相关性(P>0.05)。结论血清C-Ⅳ、LN水平与糖尿病肾病病程的发生发展密切相关,联合检测血清C-Ⅳ、LN、HbA1c、UAER可能更早、更全面地反映DN的病变程度。     

Catechin-7-O-α-L-rhamnopyranoside can reduce α-MSH-induced melanogenesis in B16F10 melanoma cells through competitive inhibition of tyrosinase

Although melanogenesis is a defense mechanism against ultraviolet (UV)-induced skin damage, abnormally excessive melanin production causes pigmentation disorders. Tyrosinase, as a key factor for melanin synthesis, plays an important role in inducing skin pigmentation. Therefore, the inhibition of tyrosinase is crucial in preventing skin pigmentation in the cosmetics and medicine fields. However, the majority of well-known tyrosinase inhibitors have been discontinued due to toxic effects on the skin or lack of selectivity and/or stability. In this study, we evaluated possible anti-melanogenic effects of catechin-7-O-α-L-rhamnopyranoside (C7R) isolated from the stem bark of Ulmus parvifolia, to discover a new tyrosinase inhibitor that has both safety and stability. When C7R was pretreated in B16F10 melanoma cells stimulated by α-melanocyte-stimulating hormone, this compound reduced melanin accumulation and murine tyrosinase activity. In line with these results, C7R inhibits tyrosinase purified from a mushroom in vitro like kojic acid and arbutin. Furthermore, C7R exhibited a competitive inhibition on a Lineweaver-Burk plot. Next, the underlying mechanisms of the C7R-mediated tyrosinase inhibitory effect were sought through docking simulation and pharmacophore analysis between tyrosinase residues and C7R. The results of these analyses showed that C7R had binding energy of -14.5kcal/mol, and indicated that C7R interacts with tyrosinase through an aromatic ring and various hydrophobic and hydrogen bonds. Together, our results suggest that C7R can be applied as a novel natural anti-melanogenic agent that inhibits tyrosinase.     

A timeline of oligodendrocyte death and proliferation following experimental subarachnoid hemorrhage

AimsWhite matter (WM) injury is a critical factor associated with worse outcomes following subarachnoid hemorrhage (SAH). However, the detailed pathological changes are not completely understood. This study investigates temporal changes in the corpus callosum (CC), including WM edema and oligodendrocyte death after SAH, and the role of lipocalin‐2 (LCN2) in those changes.MethodsSubarachnoid hemorrhage was induced in adult wild‐type or LCN2 knockout mice via endovascular perforation. Magnetic resonance imaging was performed 4 hours, 1 day, and 8 days after SAH, and T2 hyperintensity changes within the CC were quantified to represent WM edema. Immunofluorescence staining was performed to evaluate oligodendrocyte death and proliferation.ResultsSubarachnoid hemorrhage induced significant CC T2 hyperintensity at 4 hours and 1 day that diminished significantly by 8 days post‐procedure. Comparing changes between the 4 hours and 1 day, each individual mouse had an increase in CC T2 hyperintensity volume. Oligodendrocyte death was observed at 4 hours, 1 day, and 8 days after SAH induction, and there was progressive loss of mature oligodendrocytes, while immature oligodendrocytes/oligodendrocyte precursor cells (OPCs) proliferated back to baseline by Day 8 after SAH. Moreover, LCN2 knockout attenuated WM edema and oligodendrocyte death at 24 hours after SAH.ConclusionsSubarachnoid hemorrhage leads to T2 hyperintensity change within the CC, which indicates WM edema. Oligodendrocyte death was observed in the CC within 1 day of SAH, with a partial recovery by Day 8. SAH‐induced WM injury was alleviated in an LCN2 knockout mouse model.     

A pilot investigation of e‐cigarette use and smoking behaviour among patients with chronic airway disease or respiratory symptoms

BackgroundThis pilot study aimed to investigate the current status of e‐cigarettes (ECs) use patterns among patients with chronic airway disease or chronic respiratory symptoms and the effects of ECs use on respiratory and mental health.MethodsA cross‐sectional survey was conducted at the outpatient clinic of eight teaching hospitals in South Korea between November 2019 and December 2019. All adult ECs users (19 years and above) who visited the outpatient clinic as a patient with chronic airway disease or chronic respiratory symptoms were eligible to participate in this study.ResultsA total of 51 subjects responded to the survey. Most of the participants were male (92.2%) and the mean age was 41.8 years. Dominant airway diseases were asthma and chronic obstructive pulmonary disease. Most of the subjects had a history of cigarette smoking, and 19 subjects were dual users of current cigarettes and ECs. Most of the subjects started ECs use due to health‐related reasons. When comparing exclusive ECs users and dual users, St. George''s respiratory questionnaire (SGRQ) scores, the proportion of cases with moderate to severe depressive symptoms, and average Fagerstrom test for nicotine dependence scores for ECs were higher in dual users than exclusive ECs users (mean 4.64 vs. 2.38, p = 0.006), respectively.ConclusionMost of the subjects started ECs use due to health concerns, but dual users have more respiratory symptoms and higher nicotine dependence in this pilot study. One hypothesis that comes from these results is that greater nicotine dependence may influence behaviours, habits, and views about ECs. These preliminary observations need confirmation in a large cohort.