Potential Contribution of Ultrasonography Assistance for the Safe and Steady Procedure of Endoscopic Intracerebral Hematoma Evacuation: A Retrospective Cohort Study.

BACKGROUND: Endoscopic hematoma evacuation is one of the most promising procedures for the treatment of intracerebral hemorrhage (ICH) to avoid severe outcomes, such as death or dependency. However, the effect of the procedure on the functional outcome remains controversial. Thus, standardization and sophistication are required to enhance the surgical results. This study aimed to evaluate the potential efficacy of ultrasonography (US) in endoscopic hematoma evacuation. METHODS: This study included 39 consecutive patients with spontaneous supratentorial ICH who underwent endoscopic hematoma evacuation between April 2019 and July 2021. The patients were divided into two groups, namely, surgery with or without US assistance. Rebleeding and evacuation rate were set as the primary endpoints, and operation time, requirement for repeat puncture, and modified Rankin scale at discharge were set as the secondary endpoints. During surgery, the burr hole was placed, and the dura mater was widely opened. The US probe was applied on the brain surface via the burr hole to detect the depth and direction of the hematoma cavity. With US assistance, the hematoma cavity was punctured with a cannula, and the transparent port was introduced into the hematoma cavity along the tract. The hematoma was gently evacuated with the irrigation-suction instrument. RESULTS: Of the 39 cases, 9 underwent endoscopic hematoma evacuation with US assistance. Rebleeding was noted in 0 and 2 (6.7%) patients with and without US assistance, respectively (p = 0.43). The mean hematoma evacuation rates were 78.6 and 80.6% in patients with and without US assistance, respectively (p = 0.80). In all cases with US assistance, the cavity could be reached with a single tap. However, repeat puncture was required in 20 (66.7%) cases without US assistance (p = 0.04). In one case, an unexpected residual hematoma was detected using US, which was applied after hematoma evacuation and before wound closure. The operation time was not extended even if US was used during the surgery. CONCLUSIONS: US-assisted hematoma evacuation is an effective procedure that can assist in the precise insertion of the puncture cannula and exclusion of the residual hematoma. US might contribute toward improving the accuracy of each step of the procedure, thus leading to better clinical outcomes.

Proteomic identification of the proteins related to cigarette smoke-induced cardiac hypertrophy in spontaneously hypertensive rats.

Smoking increases the risk of cardiovascular diseases. The present study was designed to determine the effects of 2-month exposure to cigarette smoke (CS) on proteins in the left ventricles of spontaneously hypertensive rats (SHR) and to identify the molecular targets associated with the pathogenesis/progression of CS-induced cardiac hypertrophy. SHR and Wistar Kyoto rats (WKY) were exposed to CS at low (2 puffs/min for 40 min) or high dose (2 puffs/min for 120 min), 5 days a week for 2 months. Using the two-dimensional fluorescence difference gel electrophoresis combined with MALDI-TOF/TOF tandem mass spectrometry, we compared differences in the expression levels of proteins in the whole left ventricles induced by long-term smoking. High-dose CS mainly caused cardiac hypertrophy in SHR, but not WKY, but no change in blood pressure. Proteomic analysis identified 30 protein spots with significant alterations, with 14 up-regulated and 16 down-regulated proteins in the left ventricles of CS-exposed SHR, compared with control SHR. Among these proteins, two members of the heat shock proteins (HSP70 and HSP20) showed significant up-regulation in the left ventricles of CS high-dose SHR, and the results were confirmed by western blot analysis. Our findings suggested that HSPs play an important role in regulation of CS-induced cardiac hypertrophy.

Idarubicin, an Anthracycline, Induces Oxidative DNA Damage in the Presence of Copper (II).

BACKGROUND/AIM: The aim of the present study was to investigate whether idarubicin (IDR) induces oxidative DNA damage in the presence of copper (II). MATERIALS AND METHODS: DNA damage was evaluated by pBR322 plasmid DNA cleavage. The formation of oxidative stress markers [O2 •- and 8-hydroxy-2'-deoxyguanosine (8-OHdG)] was analysed. RESULTS: IDR induced DNA damage and O2 •- and 8-OHdG generation in the presence of copper (II). CONCLUSION: IDR induced oxidative DNA damage in the presence of copper (II). Since it has been reported that the concentration of copper in the serum of cancer patients is higher than that in healthy groups, IDR-induced oxidative DNA damage in the presence of copper (II) may play an important role in anticancer therapeutic strategies.

Oxidative DNA Damage and Apoptosis Induced by Aclarubicin, an Anthracycline: Role of Hydrogen Peroxide and Copper.

BACKGROUND/AIM: This study aimed to investigate aclarubicin (ACR)-induced oxidative DNA damage and apoptosis. MATERIALS AND METHODS: ACR-induced apoptosis was analyzed using HL-60 leukemia cells and HP100 cells, hydrogen peroxide (H2O2)-resistant cells derived from HL-60 cells. ACR-induced DNA damage was analyzed using plasmid DNA. RESULTS: HL-60 cells were more sensitive to ACR than HP100 cells. In HP100 cells, DNA ladder formation and caspase-3/7 activity induced by ACR were suppressed or delayed in comparison to those in HL-60 cells. ACR-induced DNA damage occurred in the presence of Cu(II), and scavenger experiments showed that the reactive species causing DNA damage appeared to be generated from H2O2 and Cu(I). Moreover, we detected intracellular Cu(I) induced by ACR in HL-60 cells, using CopperGREEN™, a fluorescent probe for detection of Cu(I) ion specifically. CONCLUSION: ACR-induced DNA damage and apoptosis can be accounted for by the involvement of H2O2 and Cu(I).

Synthesis, antitumor activity, and cytotoxicity of 4-substituted 1-benzyl-5-diphenylstibano-1H-1,2,3-triazoles.

Trisubstituted 5-organostibano-1H-1,2,3-triazoles (3a-f) were synthesized by the Cu-catalyzed azide-alkyne cycloaddition of various ethynylstibanes (1) with benzylazide (2) in the presence of CuBr (5 mol%) under aerobic conditions. The reaction of 5-stibanotriazoles with HCl afforded C5-unsubstituted 1,2,3-triazoles (4a-f). The antitumor activity of trisubstituted 5-organostibano-1H-1,2,3-triazoles (3a-f) and their 5-unsubstituted 1,2,3-triazoles (4a-f) were evaluated in several tumor cell lines. All 5-stibanotriazoles (3a-f) exerted an excellent antitumor activity. On the contrary, 5-unsubstituted 1,2,3-triazoles (4a-f) without a diphenylantimony group in the molecule exhibited very low antitumor activity compared with 5-stibanotriazoles (3a-f). In compounds of both the series, the substituted 4-butyl group appeared to decrease antitumor activity. However, results suggested that organometal (antimony) in the molecule was required for greater antitumor activity. In addition, all 5-stibanotriazoles (3a-f), but not all 5-unsubstituted 1,2,3-triazoles (4a-f), exhibited cytotoxicity in normal vascular endothelial cells derived from bovine aorta. Among the compounds (3b-e) that exhibited excellent antitumor activity, those with 4-methylphenyl (3b) and 1-cyclohexenyl (3e) showed relatively low cytotoxicity to vascular endothelial cells. Together, these results suggest that trisubstituted 5-organostibano-1H-1,2,3-triazoles, including compounds 3b and 3e, may serve as potential anticancer therapeutic drugs in the future.

Predictive and Prognostic Value of CYFRA 21-1 for Advanced Non-small Cell Lung Cancer Treated with EGFR-TKIs.

BACKGROUND: Tyrosine kinase inhibitors (TKIs) directed against epidermal growth factor receptor (EGFR) are important in the treatment of non-small cell lung cancer (NSCLC), especially those harboring EGFR mutations. But little is known regarding the clinical value of serum tumor marker levels measured prior to treatment. PATIENTS AND METHODS: We retrospectively reviewed 95 patients with advanced NSCLC treated with EGFR-TKIs, and inspected the relationship between serum tumor marker levels and clinical outcome. RESULTS: Forty-three patients with an elevated serum level of cytokeratin 19 fragment (CYFRA 21-1) had shorter progression-free (PFS) and overall (OS) survival than 52 patients with normal serum CYFRA 21-1 levels (99 vs. 123.5 days p=0.011; and 385 vs. 607 days, respectively, p=0.001). Regardless of EGFR mutation status, patients had shorter progression-free survival when serum CYFRA 21-1 was elevated. CONCLUSION: Serum CYFRA 21-1 level may be a predictive factor for patients with NSCLC treated with EGFR-TKIs, regardless of EGFR mutation status.

Predictive Role of CYFRA21-1 and CEA for Subsequent Docetaxel in Non-small Cell Lung Cancer Patients.

BACKGROUND/AIM: The aim of the present study was to determine the clinical value of tumor marker levels for previously treated NSCLC patients. PATIENTS AND METHODS: We retrospectively screened 113 previously treated patients with advanced NSCLC who were treated with docetaxel monotherapy regarding the pretreatment serum level of cytokeratin 19 fragment (CYFRA21-1) and carcinoembryonic antigen (CEA). RESULTS: The thirty-two patients with normal CYFRA21-1 levels and high CEA levels had a significantly higher response rate than the other 81 patients (25% vs. 8.6%, p=0.031). The former group showed statistically longer progression-free survival (PFS) and overall survival (OS) than the latter group (median PFS, 180 vs. 59 days, p<0.001; median OS, 579 vs. 255 days, p=0.002). In multivariate analysis, tumor marker levels had a significant impact on PFS and OS. CONCLUSION: Combination of the two tumor markers is a predictive and prognostic marker of docetaxel monotherapy for previously treated NSCLC patients.

Involvement of oxidative modification of proteins related to ATP synthesis in the left ventricles of hamsters with cardiomyopathy.

Inflammation enhanced by accumulation of reactive oxygen species plays an essential role in the progression of cardiovascular diseases. Using the 2D-oxyblot analysis and 2D-difference image gel electrophoresis (2D-DIGE), we compared the levels of ROS-induced carbonyl modification of myocardial proteins in the whole left ventricles between 6-week-old hamsters with dilated (TO-2) and hypertrophic cardiomyopathy (Bio14.6) and control hamsters (F1B). Then, 2D electrophoresis combined with MALDI-TOF/TOF tandem mass spectrometry detected 18 proteins with increased carbonyl level in cardiomyopathy hamsters compared with control hamster. Carbonyl modification of proteins related to ATP synthesis, including citric acid cycle and electron transport system, was observed in the hearts of hamsters with both types of cardiomyopathy. Further analysis indicated that left ventricular carbonyl production correlated negatively with succinyl-CoA:3-ketoacid-coenzyme A transferase 1 activity (r 2 = 0.60, P = 0.0007) and ATP concentration (r 2 = 0.29, P = 0.037), suggesting that protein carbonylation has negative effects on the levels of these biomolecules. Furthermore, carbonyl production significantly correlated with plasma Troponin T level (r 2 = 0.33, P = 0.026). Reduction of energy metabolism by oxidative damage may contribute to the development of left ventricular impairment in cardiomyopathy.

[Gastric metastasis from renal cell carcinoma: two case reports].

Gastric metastasis from renal cell carcinoma (RCC) is a very rare event and treatment for such patients has not been established. We report two cases of gastric metastasis from RCC. The first case was in a 67- year-old man with a past history of right radical nephrectomy for RCC (ypT3aN0M0) six years ago. The whole-body computed tomography (CT) revealed multiple lung nodules. We performed gastrointestinal endoscopy to find the primary lesion, and detected multiple submucosal tumors in the gastric body. Needle biopsy of these tumors revealed gastric metastasis from RCC. Oral sorafenib tosylate therapy was started. Twenty months later, gastrointestinal endoscopy showed only gastric erosion without malignant evidence. The second case was in a 70-year-old man complaining of epigastralgia. He had undergone right partial nephrectomy for RCC (pT1aN0M0) six years ago, and thoracoscopic wedge resection of a solitary lung nodule one year ago. Gastrointestinal endoscopy detected a solitary hyperplastic polyp in the anterior wall of the gastric body. Needle biopsy of this polyp revealed gastric metastasis from RCC. We performed laparoscopic partial gastrectomy. Gastrointestinal endoscopy and CT showed no evidence of metastasis or recurrence for 14 months after gastrectomy.

[Efficacy of prophylactic intravesical mitomycin C in patients with non-muscle-invasive bladder cancer].

Intravesical chemotherapy is beneficial for patients with non-muscle-invasive bladder cancer (NMIBC), but optimal drug and regimen selection can be controversial. Mitomycin C (MMC) is commonly used as adjuvant treatment for NMIBC. We retrospectively evaluated the outcomes of 73 patients with NMIBC who were treated with weekly doses of low-dose MMC (20 mg ; n=28 ; 38.4%) or high-dose MMC (40 mg ; n=45 ; 61.6%) for 6 weeks each, at our hospital between 2001 and 2010. Treatment outcomes were examined by Kaplan‒Meier analysis with log-rank tests. Patients in the high-dose group showed greater recurrent-free survival (61.3%) at 2 years than did patients in the low-dose group (32.6%) (P<0.05). We also found that a single early dose of pirarubicin following transurethral resection of bladder tumor improved MMC efficacy in the high-dose group. The high-dose group had a somewhat higher incidence of dysuria, urinary frequency and drug eruption, but the difference was not significant.

[Effect of change to flutamide for prostate cancer patient who developed breast pain during bicalutamide treatment (BIP-F study)].

In Japan, prostate cancer is treated with non-steroidal anti-androgen (flutamide and bicalutamide). Development of breast pain during bicalutamide treatment, in prostate cancer patients reduces their quality of life (QOL) and treatment compliance. We studied the safety and effectiveness of switching from bicalutamide to flutamide in 13 prostate cancer patients who developed breast pain during bicalutamide treatment. We estimated the change in breast pain using a face scale and the Expanded Prostate Cancer Index Composite (EPIC) and EPIC-hormone domain (HD) score. The switch to flutamide relieved breast pain in nine patients, had no effect in one patient, and increased breast pain in two patients. One patient dropped out. Furthermore, summary score and hormone function were improved with a significant difference in the EPIC-HD score. Switching to flutamide in prostate cancer patients who develop breast pain during bicalutamide is safe and effective.

The effect of vitamin E-bonded polysulfone membrane dialyzer on a new oxidative lipid marker.

The use of vitamin E-bonded cellulose membrane dialyzers has been reported to cause a decrease in oxidative lipid marker levels (Nakai et al., Ther Apher Dial 14:505-540, 1; Nakai et al., J Jpn Soc Dial Ther 45:1-47, 2; Mashiba et al., Arterioscler Thromb Vasc Biol 21:1801-1808, 3). However, few studies have identified this effect with vitamin E-bonded polysulfone membranes, and no studies report the same effect on alpha (1) antitrypsin-LDL complex, a new oxidative lipid marker. This prompted us to examine the influence of use of VPS-HA vitamin E-bonded polysulfone high-flux membrane dialyzers on this new oxidative lipid marker. The subjects were 17 patients who had been dialyzed with VPS-HA for 12 months. The subjects' baseline characteristics were as follows. Their average age was 65.6 ± 13.1 years, comprising 8 males and 9 females; hemodialysis vintage was 83.8 ± 85.4 months. Eight had chronic glomerular nephropathy and five had diabetic nephropathy. The primary outcome was defined as alpha (1) antitrypsin-LDL complex level after 12 months, as a post-study using VPS-HA. Secondary outcomes included triglycerides, total cholesterol, HDL cholesterol and LDL cholesterol levels. The data were analyzed pre-study and after 3, 6, 9 and 12 months for alpha (1) antitrypsin-LDL complex, and pre-study and post-study for the other indicators. Twelve months after switching to VPS-HA, alpha (1) antitrypsin-LDL complex, total cholesterol and LDL cholesterol had significantly decreased. Triglycerides and HDL cholesterol had not significantly changed. Hemodialysis therapy with VPS-HA was shown to decrease alpha (1) antitrypsin-LDL complex, an index of oxidative stress, and also to decrease some lipid markers.

[A case report of Cowper's syringocele in an adult treated with transurethral unroofing].

We present an adult case of Cowper's syringocele. A 19-year-old male presented with the chief complaint of persistent post-voiding dribbling 5 months after onset. Urethroscopy demonstrated a thin membrane with a small orifice on the ventral aspect distal to the external sphincter. Magnetic resonance imaging showed a restiform shadow on the left side of the corpus spongiosum. Retrograde urethrogram showed filling of diverticulum-like structure in the region of urethral bulb terminating in the urogenital diaphragm. Considering the results mentioned above, we diagnosed the patient with Cowper's syringocele. Transurethral unroofing of the Cowper's syringocele was performed with a cold knife, and the excessive tissue on the edge of syringocele was electroresected to avoid recurrence. His post-voiding dribbling resolved completely after the procedure and has not recurred in 13 months postoperatively. Cowper's syringocele is typically diagnosed presenting with hematuria, urinary tract infection, and disuria in male infants and children. Adult cases of Cowper's syringocele are rare, and only 32 cases including the present case have been reported. Proper awareness of this entity and careful evaluation are important if patients present with persistent adult-onset voiding dysfunction.

Enzymatic synthesis of caffeic acid phenethyl ester analogues in ionic liquid.

An efficient procedure for transesterification of methyl caffeate was developed to produce caffeic acid phenethyl ester analogues with Candida antarctica lipase B using an ionic liquid, 1-butyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide, as a solvent. The system provided 48.8mM 2-cyclohexylethyl caffeate and 46.9 mM 3-cyclohexylpropyl caffeate with conversion yields of 97.6% and 93.8%, respectively. Reusability of the system was investigated, and the yield of 4-phenylbutyl caffeate was increased from 30.4 to 45.7 mM when the transesterification was carried out under reduced pressure to remove a by-product, methanol. Additionally, we showed that both 2-cyclohexylethyl caffeate and 3-cyclohexylpropyl caffeate exhibit strong antiproliferative activities, which are comparable to that of 5-fluorouracil by MTT assay.

Formate excretion in urine of rats fed dimethylaminoazobenzene-rich diets: the possibility of formate formation from D-lactate.

This experiment was carried out to evaluate the possibility of degradation of d-lactate into formate and acetaldehyde. In order to induce hyperproduction of d-lactate in rats. Donryu male albino rats were fed diets containing 0.064% 3'-methyl-4-dimethylaminoazobenzene (3'-MDAB), 4'-methyl-4-dimethylaminoazobenzene (4'-MDAB) or 2-methyl-4-dimethylaminoazobenzene (2-MDAB) for 10 weeks. During the experiment, body mass, food and water intake and volume of urine were documented. Methylglyoxal, D-lactate and formate in the urine samples were determined. On the first day of the eleventh week, methylglyoxal, D-lactate, glutathione and enzymatic activities of demethylation and glyoxalase I and II in liver were measured. Methylglyoxal, D-lactate and clinical chemistry parameters of blood plasma were also measured. The levels of methylglyoxal and D-lactate in livers of rats fed 3'-MDAB were very high, while those of 2-MDAB fed-rats and the control group were the same. The fact that glyoxalase I activity and the level of glutathione, a cofactor of glyoxalase I, were high in the livers of the 3'-MDAB-fed rats can explain the elevated levels of methylglyoxal and D-lactate in the liver. The most striking results were the elevated formate levels in the urine of rats fed 3'- and 4'-MDAB in a precancerous state. The degradation of D-lactate, an end product of the methylglyoxal bypass, into acetaldehyde and formate was suggested as a possible way to explain the results.