Humans ; Astrocytes ; Neocortex ; Epilepsy/therapy* ; Tosylarginine Methyl Ester

To investigate the application of bromocresol green Colorimetry (BCG) method in measuring serum albumin (ALB) and to evaluate its influencing factors in different diseases. This study was a cross-sectional study that included 128 people admitted to the department of nephrology, department of general surgery, department of infectious diseases and other departments of the Third Xiangya Hospital of Central South University in July 2021. They were divided into groups according to disease types, including chronic kidney disease group (47 cases), liver disease group (40 cases), other diseases group (41 cases), serum ALB was detected by BCG method and immunoturbidimetry at the same time, and the results were expressed as ALB_BCG and ALB_I respectively, each group was subdivided into three subgroups according to ALB_I results: relatively high-value subgroup, relatively intermediate-value subgroup and relatively low-value subgroup of albumin. ALB_I and ALB_BCG were compared in all groups and subgroups. Passing-Bablok regression and Bland-Altman diagram analysis were used to evaluate the application of ALB_BCG in each group. Immunoturbidimetry was used as a reference method to evaluate the bias of ALB_BCG, and the differences between ALB_I and ALB_BCG were shown as follows:ΔALB= ALB_BCG-ALB_I. Pearson correlation analysis and multiple linear regression analysis were used to assess the correlation between ΔALB and ALB autoconcentration (ALB_I), α₁-globulin, α₂-globulin, β₁-globulin, β₂-globulin, γ-globulin, creatinine (Cr), urea (UN), uric acid (UA), aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (TBil), direct bilirubin (DBil), and C-reactive protein (CRP) levels.The results showed that ALB_BCG were higher than ALB_I in the relative low subgroups of total patients group, chronic kidney disease group, liver disease group and other disease groups, and the differences were statistically significant (t value was 8.025, 6.878, 2.628, 4.915, respectively, P<0.05). In the relatively high value subgroup, ALB_BCG was lower than ALB_I, and the differences were statistically significant in the relative high value subgroup of total patients group, liver disease group and other disease groups (t value was -4.388, -2.927, -3.979, P<0.05). Passing-Bablok regression and Bland-Altman analysis showed that the BCG method had proportional bias. In the chronic kidney disease group, the concentrations of ALB_I and Cr had the greatest influence on BCG bias, and the regression model equation was ΔALB=5.437-0.146× Alb_I-0.001 ×Cr, R²=0.505. In the liver disease group, the concentrations of ALB_I, α₁-globulin, β₁-globulin had the greatest influence on BCG bias, and the regression model equation was ΔALB=3.652-0.230×ALB_I+0.398×α₁-globulin+1.171×β₁-globulin, R²=0.658. In the other disease group, the concentration of ALB_I and α₂-globulin had the greatest influence on BCG bias, and the regression equation was ΔALB=5.558-0.225×Alb_I-0.281×α₂-globulin, R²=0.646. The BCG method has a proportion error, and its bias may lead to unacceptable differences. BCG method is mainly affected by the concentration of ALB itself, and may also be affected by α₁-globulin, α ₂-globulin, β₁-globulin, Cr.
BCG Vaccine ; Bilirubin ; Bromcresol Green ; Colorimetry ; Cross-Sectional Studies ; Globulins ; Humans ; Renal Insufficiency, Chronic ; Retrospective Studies ; Serum Albumin/analysis*

The aim of the present study was to determine whether oncologic outcomes and adverse events associated with active on/off intermittent antiandrogen monotherapy (daily bicalutamide, 50 mg per day) are comparable with those of standard external beam radiation therapy (EBRT) or combined androgen blockade (CAB) therapy in prostate cancers with positive surgical margins after radical prostatectomy. Two hundred twenty-three patients with positive surgical margins post-radical prostatectomy who underwent active surveillance (AS, n = 32), EBRT without hormone therapy (n = 55), intermittent antiandrogen monotherapy without EBRT (IAAM, n = 50), or CAB without EBRT (n = 86), between 2007 and 2014, were reviewed retrospectively. Pathologic outcomes, biochemical recurrence rates, radiological disease progression, and adverse events were collected from medical records. Biochemical recurrence rates, biochemical recurrence-free survival rates, and radiological recurrence were not different between the groups (P = 0.225, 0.896, and 0.284, respectively). Adverse event rates and severities were lower for IAAM compared with EBRT or CAB (both P < 0.05), but were comparable to those for AS (P = 0.591 and 0.990, respectively). Grade ≥3 adverse events were not reported in the IAAM or AS groups. Erectile dysfunction and loss of libido rates were lower in the IAAM group compared with the EBRT and CAB groups (P = 0.032). Gastrointestinal complications were more frequently reported in the EBRT group (P = 0.008). Active on/off IAAM treatment might be an appropriate treatment option for patients with positive surgical margins after radical prostatectomy. Furthermore, regarding oncologic outcomes, IAAM was comparable to standard EBRT but had a milder adverse event profile.
Aged ; Aged, 80 and over ; Androgen Antagonists/adverse effects* ; Anilides/adverse effects* ; Antineoplastic Agents/adverse effects* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Chemotherapy, Adjuvant/adverse effects* ; Disease-Free Survival ; Humans ; Male ; Neoplasm Recurrence, Local/blood* ; Neoplasm, Residual ; Nitriles/adverse effects* ; Prostate-Specific Antigen/blood* ; Prostatectomy ; Prostatic Neoplasms/therapy* ; Radiotherapy, Adjuvant/adverse effects* ; Retrospective Studies ; Tosyl Compounds/adverse effects*

Even in the era of novel targeted agents, switching to a second-line nonsteroidal antiandrogen (NSAA) is still widely used in treating metastatic castration-resistant prostate cancer (mCRPC), especially in undeveloped countries. However, whether prior treatment with a second-line NSAA would impact the efficacy of abiraterone acetate (Abi) remains uncertain. In the current study, 87 mCRPC patients treated with Abi were analyzed. Among them, 21 were treated with a second-line NSAA (from bicalutamide to flutamide) before receiving abiraterone, while the remaining 66 received Abi directly. Therapeutic efficacy of Abi was compared between those with and without prior second-line NSAA using Kaplan-Meier curves, log-rank test, and Cox regression models. The therapeutic efficacy of Abi was similar between those with or without the prior switching treatment of flutamide, in terms of either prostate-specific antigen progression-free survival (PSA-PFS, 5.5 vs 5.6 months, P = 0.967), radiographic progression-free survival (rPFS, 12.8 vs 13.4 months, P = 0.508), overall survival (OS, not reached vs 30.6 months, P = 0.606), or PSA-response rate (71.4% [15/21] vs 60.6% [40/66], P = 0.370). This is the first time that the impact of prior switching of treatment to a second-line NSAA on the efficacy of Abi in mCRPC patients has been addressed. Our data support that, use of prior sequential bicalutamide and flutamide does not seem to preclude response to abiraterone, although larger cohort studies and, ideally, a randomized controlled trial are needed. These findings will facilitate doctors' decision-making in the treatment of mCRPC patients, especially for those with previous experience of switching NSAA second-line treatments in the clinic.
Abiraterone Acetate/therapeutic use* ; Aged ; Aged, 80 and over ; Androgen Antagonists/therapeutic use* ; Anilides/therapeutic use* ; Antineoplastic Agents, Hormonal/therapeutic use* ; Disease-Free Survival ; Female ; Flutamide/therapeutic use* ; Humans ; Kaplan-Meier Estimate ; Male ; Nitriles/therapeutic use* ; Nonsteroidal Anti-Androgens/therapeutic use* ; Prostate-Specific Antigen/analysis* ; Prostatic Neoplasms, Castration-Resistant/drug therapy* ; Retrospective Studies ; Survival Analysis ; Tosyl Compounds/therapeutic use* ; Treatment Outcome

Objective: To investigate the clinical effects of integrated traditional Chinese and Western medicine in the treatment of castration-resistant prostate cancer (CRPC). METHODS: A total of 54 CRPC patients were randomly divided into a control and a trial group, all treated by endocrine therapy (oral Bicalutamide at 50 mg per d plus subcutaneous injection of Goserelin at 3.6 mg once every 4 wk) and chemotherapy (intravenous injection of Docetaxel at 75 mg/m2 once every 3 wk plus oral Prednisone at 5 mg bid), while the latter group by Fuyang Huayu Prescription (a Traditional Chinese Medicine ［TCM］ prescription for tonifying yang and dispersing blood stasis) in addition, for a course of 24 weeks. Comparisons were made between the two groups of patients in the level of serum prostate-specific antigen (PSA), Karnofsky physical condition scores, function assessment of cancer therapy-prostate (FACT-P) scores, and TCM symptoms scores before and after 12 or 24 weeks of treatment. RESULTS: Compared with the baseline, the serum PSA level was significantly decreased after 12 weeks of treatment both in the control (［25.9 ± 39.3］ vs ［20.0 ± 21.1］ μg/L, P <0.05) and in the trial group (［22.1 ± 33.9］ vs ［17.9 ± 19.1］ μg/L, P <0.05), with no statistically significant differences between the two groups (P >0.05). At 24 weeks, however, the PSA levels in the control and trial groups were slightly increased to (23.1 ± 28.4) and (19.6 ± 23.5) μg/L, respectively, with no statistically significant differences in between (P >0.05). Karnofsky, FACT-P and TCM symptoms scores were all markedly improved in the trial group after 12 weeks of treatment (P <0.05) and remained stable at 24 weeks, but not in the control group either at 12 or at 24 weeks (P >0.05). CONCLUSIONS TCM Fuyang Huayu Prescription combined with endocrine therapy and chemotherapy is effective for CRPC.
Anilides ; administration & dosage ; Antineoplastic Agents, Hormonal ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Docetaxel ; Drug Administration Schedule ; Goserelin ; administration & dosage ; Humans ; Male ; Nitriles ; administration & dosage ; Prednisone ; administration & dosage ; Prostate-Specific Antigen ; blood ; Prostatic Neoplasms, Castration-Resistant ; blood ; drug therapy ; Taxoids ; administration & dosage ; Tosyl Compounds ; administration & dosage ; Treatment Outcome

BACKGROUND: Rapid detection of carbapenemase-producing gram-negative bacilli (GNB) is required for optimal treatment of infected patients. We developed and assessed a new disk carbapenemase test (DCT). METHODS: Paper disks containing 0.3 mg of imipenem and bromothymol blue indicator were developed, and the performance of the DCT were evaluated by using 742 strains of GNB with or without carbapenemases. RESULTS: The paper disks were simple to prepare, and the dried disks were stable at -20℃ and at 4℃. The DCT detected 212 of 215 strains (98.6% sensitivity with 95% confidence interval [CI] 96.0-99.5%) of GNB with known class A (KPC and Sme) and class B (NDM, IMP, VIM, and SIM) carbapenemases within 60 min, but failed to detect GES-5 carbapenemase. The DCT also detected all two Escherichia coli isolates with OXA-48, but failed to detect GNB with OXA-232, and other OXA carbapenemases. The DCT showed 100% specificity (95% CI, 99.2-100%) in the test of 448 imipenem-nonsusceptible, but carbapenemase genes not tested, clinical isolates of GNB. CONCLUSIONS: The DCT is simple and can be easily performed, even in small laboratories, for the rapid detection of GNB with KPC, NDM and the majority of IMP, VIM, and SIM carbapenemases.
Anti-Bacterial Agents/*pharmacology ; Bacterial Proteins/*metabolism ; Bromthymol Blue/chemistry ; Drug Resistance, Bacterial ; Gram-Negative Bacteria/drug effects/*enzymology ; Imipenem/pharmacology ; Microbial Sensitivity Tests/*methods ; Paper ; beta-Lactamases/*metabolism

OBJECTIVETo establish a labeling method for a specific lung cancer-targeting small molecule peptide cNGQGEQc with ¹³¹I and observe the radioactivity distribution of the labeled peptide in rabbits using single-photon emission computed tomography (SPECT).

METHODSChloramine-T method was used for ¹³¹I labeling of the tyrosine amino group on cNGQGEQc, and the labeling efficiency and radiochemical purity of ¹³¹I-cNGQGEQc were determined with paper chromatography. The stability of ¹³¹I-cNGQGEQc in saline and human serum was assessed after incubation in water bath at 37 degrees celsius; for 24 h. The octanol-water partition coefficient lg P (the radioactivity counting ratio of ¹³¹I-cNGQGEQc dissolved in 100 µl octanol or in 100 µl saline) was calculated. SPECT was performed in 3 male New Zealand white rabbits after intravenous injection of ¹³¹I-cNGQGEQc to observe the dynamic distribution of the peptide with the time-radioactivity curve (T-A curve) of the region of interest (ROI).

RESULTSWith a labeling efficiency of 90%, ¹³¹I-cNGQGEQc showed a radiochemical purity of was 95% after purification with HPLC. The radiochemical purity of ¹³¹I-cNGQGEQc was (93.12 ± 1.18)% and (88.34 ± 5.43)% after intubation in saline and human serum for 24 h, respectively. The octanol-water partition coefficient lg P of ¹³¹I-cNGQGEQc was -1.75, suggesting its hydrosolubility. In rabbits with intravenous injection of ¹³¹I-cNGQGEQc, SPECT visualized the kidneys at 1 min after the injection; the imaging of the heart and liver became attenuated at 5 min when the bladder was visualized with an increasing radioactivity. The radioactivity of the soft tissues began to fade at 30 min. No gallbladder visualization was detected, and the radioactivity of the abdomen remained low. No obvious radioactivity concentration was observed in the thyroid and stomach. The T-A curves of the ROI of all the tissues and organs descended over time.

CONCLUSIONRadiolabeling of cNGQGEQc with ¹³¹I is simple and highly efficient. ¹³¹I-cNGQGEQc has good stability in vitro and good distribution characteristics for in vivo imaging, and is cleared mainly by renal excretion due to its hydrosolubility. These results provide experimental basis for further studies of diagnosis and therapy of lung cancer with targeting polypeptide.

Animals ; Antineoplastic Agents ; pharmacokinetics ; Chloramines ; Humans ; Iodine Radioisotopes ; chemistry ; Lung Neoplasms ; Male ; Peptides ; pharmacokinetics ; Rabbits ; Radiopharmaceuticals ; pharmacokinetics ; Tissue Distribution ; Tomography, Emission-Computed, Single-Photon ; Tosyl Compounds

OBJECTIVETo search for an effective hormonal therapy for delaying the progression of prostate cancer to androgen-independent prostate cancer (AIPC).

METHODSThis study included 93 cases of prostate cancer confirmed by transrectal ultrasound-guided biopsy, 22 treated by bilateral orchiectomy plus bicalutamide as a continuous androgen deprivation (CAD) therapy, and the other 71 by the intermittent androgen deprivation (IAD) therapy, the latter divided into a standard IAD group (n = 29) and a modified IAD group (n = 42) to be treated by maximum androgen blockage (MAB) until the serum PSA level decreased to less than 0.2 microg/L and the medication was maintained for 3 months. Entering the intermittent period, the patients of the standard IAD group discontinued medication, while those in the modified IAD group withdrew luteinizing hormone-releasing hormone analogue (LHRH-a) but continued the use of bicalutamide. MAB was resumed in these two groups when serum PSA manifested a continuous rise and went up to 4 microg/L until prostate cancer progressed to AIPC. Comparisons were made among the CAD, standard IAD and modified IAD groups in the follow-up time, time of progression to CRPC and treatment cycles.

RESULTSThe three groups of patients were well balanced in terms of demographics, baseline characteristics and follow-up time. The median times of progression to AIPC in the CAD, standard IAD and modified IAD groups were (26.50 +/- 4.15), (30.00 +/- 7.83) and (34.93 +/- 5.08) months, respectively, with statistically significant differences between the modified IAD group and the CAD (P = 0.001) and standard IAD (P = 0.032), but not between the latter two groups (P = 0.143). Kaplan-Meier survival curves showed a significantly longer median time of progression to AIPC in the modified than in the standard IAD group (P = 0.01). The mean cycle length was (16.13 +/- 3.33) months for the standard IAD group and (19.58 +/- 4.30) months for the modified IAD group, and the time off treatment of the first cycle was (9.6 +/- 3.2) months in the former and (14.2 +/- 3.7) months in the latter, with significant difference between the two groups (P = 0.001).

CONCLUSIONCompared with CAD and standard IAD, modified IAD therapy can significantly prolong the time of progression to AIPC in patients with prostate cancer.

Aged ; Aged, 80 and over ; Androgen Antagonists ; administration & dosage ; therapeutic use ; Anilides ; administration & dosage ; therapeutic use ; Antineoplastic Agents, Hormonal ; administration & dosage ; therapeutic use ; Disease Progression ; Humans ; Male ; Middle Aged ; Nitriles ; administration & dosage ; therapeutic use ; Prognosis ; Prostatic Neoplasms ; diagnosis ; drug therapy ; Tosyl Compounds ; administration & dosage ; therapeutic use ; Treatment Outcome

OBJECTIVETo establish osteoblast apoptosis model induced by gingipains, and to examine the expression of pro-apoptotic protein Bcl-2 interacting mediator (Bim), Bcl-2 associated X protein (Bax) and Bcl-2 antagonist/killer (Bak).

METHODSGingipain and gingipain acticity were extracted and measured. Mouse osteoblast cell line MC3T3-E1 cells were cultured in the presence of 0.453, 0.906, 1.812 U/L gingipains for 0, 16, 24 and 48 h. Apoptosis was examined by 4',6-diamidino-2-phenylindole (DAPI) staining or annexin V/propidine iodide (PI) staining.Protein expression of Bim, Bax and Bak was determined by Western blotting after osteoblasts were cultured with 1.812 U/L gingipain for 0, 4, 8, 16, 24 and 48 h. Osteoblasts were cultured with 1.812 U/L gingipain which had been inhibited with N-alpha-tosyl L-lysyl-chlorom ethylketone (TLCK). Western blotting was used to detect Bim expression and DAPI staining to measure apoptosis.

RESULTSArginine-specific proteinases (Rgp) activity was (18.11 ± 2.11) U/L and specific proteinases (Kgp) was (1.02 ± 0.25) U/L. Percentage of osteoblast apoptosis induced by 1.812 U/L gingipain rose to (6.31 ± 0.37)% after 16 h, and reached (11.20 ± 0.35)% at 24 h and (10.80 ± 0.46)% after 48 h with DAPI staining. Annexin V/PI staining supported the result from DAPI staining.Bim protein level increased during osteoblast apoptosis, the relative fold rose to (0.31 ± 0.03) after 4 h (about 2 fold compared to control), peaking at 24 h (0.57 ± 0.05, 3-4 fold compared to control). Proteinase inhibitor TLCK effectively blocked the activity of gingipain and inhibited up-regulation of Bim induced by gingipains from (0.58 ± 0.04) to (0.14 ± 0.03). The percentage of osteoblast apoptosis decreased from (11.20 ± 0.35)% to (4.31 ± 0.38)% in the presence of TLCK. Expression of Bax remained unchanged when cells were cultured with or without gingipains. Bak was under the detectable level in MC3T3-E1.

CONCLUSIONS1.812 U/L gingipains induced osteoblast apoptosis. Protein expression of Bim was up-regulated during cell apoptosis and was down-regulated when gingipain inhibited with TLCK, suggesting that Bim was involved in osteoblast apoptosis induced by gingipain. Inhibition of Bim protein expression protected osteoblast from apoptosis.

Adhesins, Bacterial ; pharmacology ; Animals ; Apoptosis ; drug effects ; Apoptosis Regulatory Proteins ; metabolism ; Bcl-2-Like Protein 11 ; Cell Line ; Cysteine Endopeptidases ; pharmacology ; Humans ; MCF-7 Cells ; Membrane Proteins ; metabolism ; Mice ; Osteoblasts ; cytology ; metabolism ; Proto-Oncogene Proteins ; metabolism ; Tosyllysine Chloromethyl Ketone ; pharmacology ; bcl-2 Homologous Antagonist-Killer Protein ; metabolism ; bcl-2-Associated X Protein ; metabolism

PURPOSE: The purpose of this study was to investigate the role of mast cells and their product, histamine and leukotriene in ischemia-reperfusion injury. METHODS: Forty Sprague-Dawley rats were divided into four groups. (Group I: Control group without ischemia, Group II: Normal saline with ischemia, Group III: Cimetidine with ischemia, Group IV: Zafirlukast with ischemia) Skin flap was elevated and ischemic insult was given by clamping the artery for 12 hours. Before reperfusion, the rats were treated with saline, cimetidine and zafirlukast. Flap survival was evaluated at 7 days. Neutrophil counts, mast cell counts were evaluated 24 hours after reperfusion. RESULTS: Flap survival rate in the control group was 92.33%, whereas normal saline group had 37.34% survivals. Cimetidine and zafirlukast treated group showed significantly higher survival rates than normal saline group. The neutrophil and mast cell counts in cimetidine and zafirlukast treated group were significantly decreased than normal saline group. Cimetidine treated group showed higher survival rate and lower cell counts than zafirlukast treated group. CONCLUSION: The administration of cimetidine and zafirlukast can decrease neutrophils and mast cells caused by ischemia-reperfusion and increase flap survivals. It is suggests that antihistamine and leukotriene receptor antagonist have protective effect against ischemia-reperfusion injury to skin flap in rat.
Animals ; Arteries ; Cell Count ; Cimetidine ; Constriction ; Histamine ; Ischemia ; Mast Cells ; Neutrophils ; Rats ; Rats, Sprague-Dawley ; Receptors, Leukotriene ; Reperfusion ; Reperfusion Injury ; Skin ; Survival Rate ; Tosyl Compounds