Genetic polymorphisms of selected DNA repair genes, estrogen and progesterone receptor status, and breast cancer risk.

PURPOSE: Genetic polymorphisms of DNA repair genes seem to determine the DNA repair capacity, which in turn may affect the risk of breast cancer. To evaluate the role of genetic polymorphisms of DNA repair genes in breast cancer, we conducted a hospital-based case-control study of Korean women. EXPERIMENTAL DESIGN: We included 872 incident breast cancer cases and 671 controls recruited from several teaching hospitals in Seoul from 1995 to 2002. Twelve loci of selected DNA repair genes were genotyped by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (XRCC2 Arg188His, XRCC4 921G > T, XRCC6 1796G > T, LIG4 1977T/C, RAD51 135G > C, 172G > T, RAD52 2259C > T, LIG1 551A > C, ERCC1 8092A > C, 354C > T, hMLH1 -93G > A, and Ile219Val). RESULTS: We found that the RAD52 2259 CT or TT, hMLH1 -93 GG, and ERCC1 8092 AA genotypes were associated with breast cancer risk after adjustment for known risk factors [odds ratio (OR), 1.33; 95% confidence interval (95% CI), 1.02-1.75; OR, 1.31; 95% CI, 0.99-1.74; and OR, 0.58; 95% CI, 0.38-0.89, respectively]. When Bonferroni's method was used to correct for multiple comparisons for nine polymorphisms with P = 0.005, all of these associations were not significant. However, the effects of RAD52 2259 CT or TT and ERCC1 354 CT or TT genotypes were more evident for the estrogen/progesterone receptor-negative cases (OR, 2.03; 95% CI, 1.24-3.34 and OR, 1.99; 95% CI, 1.35-2.94, respectively). CONCLUSION: Our findings suggest that genetic polymorphisms of RAD52, ERCC1, and hMLH1 may be associated with breast cancer risk in Korean women.     

Amphiphilic amino acid copolymers as stabilizers for the preparation of nanocrystal dispersion

The recent advance of particle size engineering in nanometer ranges has widened the formulation opportunities of relatively water-insoluble drugs. However, the ‘nanoformulation’ suffers from a lack of systematic understanding about the requirements of polymeric stabilizers. Furthermore, the polymers that can be used for the preparation of nanocrystals are so limited that finding a proper stabilizer for a given formulation is often difficult. In this study, amino acid copolymers whose properties can systematically be tailored are developed, and their morphological and compositional effects are investigated. Copolymers containing lysine (K) as their hydrophilic segments, and phenylalanine (F) or leucine (L) as their hydrophobic segments successfully produce stable nanocrystals (200–300 nm) in water, while copolymers of K and alanine (A) could not generate nanosized particles. Not the morphology but the hydrophobicity of copolymers seems to be a critical parameter in the preparation of drug nanocrystals by wet comminution. The effective stabilization performance of copolymers requires the hydrophobic moiety content to be higher than 15 mol%. Comminution for only 5 min is long enough for nanocrystal preparation, and the crystallinity of drug is found intact after the processing.     

Larynx preservation surgery in pyriform sinus cancer

As a general rule, surgery, whenever possible followed by irradiation, is considered to be a standard treatment for pyriform sinus cancer. In early primary lesions, many different approaches have been tried for larynx preservation. From 1990-1997, 7 patients with pyriform sinus carcinoma without the involvement of pyriform sinus apex were treated with partial laryngopharyngectomy at the Asan Medical Center. Three patients were T1 stage and four were T2. All patients had nodal metastases and were treated with neck dissection and postoperative radiotherapy. Follow-up period was 1-8 years. One regional recurrence and one distant metastasis occurred; however, there was no recurrence at the primary site. The voices of all the patients were saved. The most uncomfortable postoperative symptom was mild aspiration. From these results, we can conclude that partial laryngopharyngectomy with neck dissection might be the favorable treatment modality for selected cases of pyriform sinus cancer.     

Malignant transformation of nevus sebaceous to basal-cell carcinoma: Case series,literature review,and management algorithm

Nevus sebaceous (NS) is a common congenital hamartoma of the skin composed predominantly of sebaceous glands. Although most NS are benign skin tumors, malignant transformations have been reported. There is still controversy about the lifetime risk of malignant degeneration and precise surgical criteria. This study reports cases of malignant degeneration and suggests a surgical treatment algorithm. The medical records of patients with basal-cell carcinoma (BCC) arising from NS between January 2001 and January 2021 were retrospectively reviewed. Patient demographics including lesion location, and tumor size were investigated. The symptoms, histological findings before and after excision, complications, and recurrence during 2-year follow-up periods were investigated. Ten patients were identified with BCC arising from NS lesions. All patients were female and the mean age was 52.11 years. All patients complained of sudden morphological changes, the most common type being rapid color changes. Two cases had histological findings that showed a miss-match between punch biopsy and excisional biopsy results. No recurrence was detected 2 years after surgeries in any patients. Cases after third stage, especially in over 40 years who report morphologic changes, should undergo total surgical excision as the first approach, with strong suspicion of malignant degeneration.     

Orthopedic Patients with Mental Disorder: Literature Review on Preoperative and Postoperative Precautions

Because of the increasing global trend of patients with mental disorders, orthopedic surgeons are more likely to encounter orthopedic patients with mental disorders in clinical settings. Identifying the characteristics of these patients and implementing psychiatric management can affect the clinical outcome of orthopedic treatment. Thus, orthopedic surgeons need to assess the psychiatric medical history of orthopedic patients with mental disorders before surgery and understand the psychological and behavioral patterns of patients with mental disorders. In addition, appropriate psychiatric consultations and evaluations are necessary to prevent worsening of mental disorders before and after surgery.     

The Alleviation of Gut Microbiota-Induced Depression and Colitis in Mice by Anti-Inflammatory Probiotics NK151, NK173, and NK175

Gut microbiota dysbiosis is strongly associated with psychiatric disorders and inflammatory bowel disease (IBD). Herein, we examined whether the fecal microbiota of IBD patients with depression (IBDD) and their gut microbiota culture (iGm) could cause depression and colitis in mice and anti-inflammatory probiotics could mitigate depression in iGm-transplanted or immobilization stress (IS)-exposed mice. Fecal microbiota transplantation (FMT) from IBDD patients, which exhibited Enterobacteriaceae-rich gut microbiota, and its gut microbiota culture (iGm) increased depression-like behaviors in mice. Their treatments heightened the blood lipopolysaccharide (LPS) level and colonic IL-1β and IL-6 expression. However, FMT from healthy volunteers or sulfasalazine treatment alleviated cGm-induced depressive-like behaviors and hippocampal and colonic inflammation in mice. Moreover, oral administration of Lactobacillus plantarum NK151, Bifidobacterium longum NK173, and Bifidobacterium bifidum NK175, which inhibited LPS-induced IL-6 expression in macrophages, alleviated cGm-induced depression-like behaviors, hippocampal NF-κB⁺Iba1⁺ cell numbers and IL-1β and IL-6 expression, blood LPS, IL-6, and creatinine levels, and colonic NF-κB⁺CD11c⁺ number and IL-1β and IL-6 expression in mice. Treatment with NK151, NK173, or NK175 mitigated immobilization stress (IS)-induced depressive-like behaviors, neuroinflammation, and gut inflammation in mice. NK151, NK173, or NK175 also decreased IS-induced blood LPS, IL-6, and creatinine levels. The transplantation of Enterobacteriaceae-rich gut microbiota can cause depression and colitis, as IS exposure, and anti-inflammatory NK151, NK173, and NK175, may alleviate stress-induced fatigue, depression, and colitis by regulating the expression of proinflammatory and anti-inflammatory cytokines through the suppression of gut bacterial LPS.     

维药胡桐泪的多糖含量测定及其糖组成分析

目的:测定市场上实际流通的商品胡桐泪药材中多糖的含量并对其单糖组成进行分析,以多糖为指标评价药材质量。方法:采用苯酚-硫酸法对总多糖进行含量测定;应用核磁共振氢谱(1H-NMR)分析单糖组成;运用高效凝胶渗透色谱(HPGPC)测定总多糖的分子量分布。结果:以葡萄糖计,4批新式胡桐泪总多糖含量平均值为(7.36±1.74)%,6批老式胡桐泪总多糖含量平均值为(1.53±0.99)%;新式与老式胡桐泪总多糖的单糖组成相似,主要由阿拉伯糖和半乳糖组成,还含有木糖、甘露糖、鼠李糖等,部分样品尚含有较高含量的葡萄糖;新旧类型样品总多糖在分子量分布上存在较大差异。结论:新式胡桐泪的总多糖含量平均值较老式高,以多糖含量为评价指标时,新式样品总体质量较老式更好;应用核磁共振氢谱可以快速、准确地鉴定单糖组成。     

Preparation and evaluation of immediate release ibuprofen solid dispersions using polyethylene glycol 4000

To improve its dissolution, ibuprofen solid dispersions (SDs) were prepared in a relatively easy and simple manner, characterized by scanning electron microscopy (SEM), differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FT-IR), and evaluated for solubility, in-vitro drug release and oral bioavailability of ibuprofen in rats. Loss of individual surface properties during melting and resolidification as revealed by SEM micrographs indicated the formation of effective SDs. Absence or shifting towards the lower melting temperature of the drug peak in SDs and physical mixtures in DSC study indicated the possibilities of drug-polymer interactions. FT-IR spectra showed the presence of drug crystalline in SDs. Quicker release of ibuprofen from SDs in rat intestine resulted in a significant increase in AUC and Cmax, and a significant decrease in Tmax over pure ibuprofen. Preliminary results from this study suggested that the preparation of fast dissolving ibuprofen SDs by low temperature melting method using polyethylene glycol 4000 (PEG 4000) as a meltable hydrophilic polymer carrier could be a promising approach to improve solubility, dissolution and absorption rate of ibuprofen.     

Brief Report: Adenosine A2A receptor blockade prevents cisplatin-induced impairments in neurogenesis and cognitive function

Chemotherapy-induced cognitive impairment (CICI) has emerged as a significant medical problem without therapeutic options. Using the platinum-based chemotherapy cisplatin to model CICI, we revealed robust elevations in the adenosine A_2A receptor (A_2AR) and its downstream effectors, cAMP and CREB, by cisplatin in the adult mouse hippocampus, a critical brain structure for learning and memory. Notably, A_2AR inhibition by the Food and Drug Administration–approved A_2AR antagonist KW-6002 prevented cisplatin-induced impairments in neural progenitor proliferation and dendrite morphogenesis of adult-born neurons, while improving memory and anxiety-like behavior, without affecting tumor growth or cisplatin’s antitumor activity. Collectively, our study identifies A_2AR signaling as a key pathway that can be therapeutically targeted to prevent cisplatin-induced cognitive impairments.