Endothelium-dependent relaxation and vasospasm in the single-hemorrhage canine model

Abstract

We have investigated the relationship between angiographic vasospasm and the ability of spastic vessels to relax in response to agents which promote release of endothelium derived relaxing factor. Vasospasm was induced in dogs by the 'single hemorrhage' technique. Animals received a single intracisternal injection of blood, blood activated with thromboplastin or collagen, or inert material, and angiograms were obtained day 0 and day 7. Vasospasm was estimated by measuring the ratio of the diameter of the vessel before and after treatment. Rings of cerebral artery obtained from these animals were suspended in a standard organ- bath arrangement, contracted with prostaglandin F2(X and then treated with increasing doses of adenosine triphosphate or bradykinin, both of which cause relaxation by an endothelium-dependent process. The arteries from animals with moderate to severe vasospasm showed a response to bradykinin and adenosine- triphosphate which was reduced, absent or converted to a contraction, when compared with normal vessels. Vessels in which vasospasm was mild or absent relaxed as expected to these agents. The reduction in vessel diameter showed a highly significant correlation with the reduction in relaxation to bradykinin or adenosine-triphosphate. These results have demonstrated that impairment of endothelium-dependent vasorelaxation correlates with the existence of vasospasm. [Neurol Res 1996; 18: 553-558]     

Clinical outcomes and nadir prostate-specific antigen (PSA) according to initial PSA levels in primary androgen deprivation therapy for metastatic prostate cancer

Purpose

To investigate the clinical outcomes of metastatic prostate cancer patients and the relationship between nadir prostate-specific antigen (PSA) levels and different types of primary androgen deprivation therapy (PADT). This study utilized data from the Japan Study Group of Prostate Cancer registry, which is a large, multicenter, population-based database.

Methods

A total of 2982 patients treated with PADT were enrolled. Kaplan–Meier analysis was used to compare progression-free survival (PFS) and overall survival (OS) in patients treated using combined androgen blockade (CAB) and non-CAB therapies. The relationships between nadir PSA levels and PADT type according to initial serum PSA levels were also investigated.

Results

Among the 2982 enrolled patients, 2101 (70.5 %) were treated with CAB. Although CAB-treated patients had worse clinical characteristics, their probability of PFS and OS was higher compared with those treated with a non-CAB therapy. These results were due to a survival benefit with CAB in patients with an initial PSA level of 500–1000 ng/mL. Nadir PSA levels were significantly lower in CAB patients than in non-CAB patients with comparable initial serum PSA levels.

Conclusions

A small survival benefit for CAB in metastatic prostate cancer was demonstrated in a Japanese large-scale prospective cohort study. The clinical significance of nadir PSA levels following PADT was evident, but the predictive impact of PSA nadir on OS was different between CAB and non-CAB therapy.

     

Secondary pouchitis in a pediatric patient successfully treated by salvage surgery

Apart from primary pouchitis, patients with secondary pouchitis caused by surgical complications require surgical management. The use of abdomino‐anal salvage surgery to treat secondary pouchitis caused by surgical complications in pediatric patients with ulcerative colitis (UC) has not been reported in detail. A girl was diagnosed with UC at 8 years old. She underwent restorative proctocolectomy with ileal pouch–anal anastomosis (IPAA) at 9 years old. She presented at 12 years old because of chronic antibiotic‐refractory pouchitis. The fistula and stricture failed to improve despite multiple local salvage surgeries and ileostomy construction. At 15 years old, she underwent redo IPAA. The patient was well at 20 years old with no signs of pouchitis. Early treatment by abdomino‐anal salvage surgery might be indicated to improve quality of life in pediatric patients with secondary pouchitis caused by surgical complication unresponsive to defunctioning and local salvage surgery.     

Uterine smooth muscle cells increase invasive ability of endometrial carcinoma cells through tumor–stromal interaction

The incidence of lymph node metastasis by endometrial carcinoma (EMCA) increases with the depth of myometrial invasion, and this depth of invasion has been found to have a major impact on the outcome. In the present study, we assessed the effect of tumor–stromal interactions on the invasive behavior of EMCA cells and examined the involvement of SDF-1alpha/CXCL12-CXCR4 in the interaction of EMCA cells and uterine smooth muscle cells (UtSMCs). We investigated whether SDF-1alpha/CXCL12 produced and secreted from UtSMCs induces EMCA cell migration by using 5 human EMCA cell lines such as AMEC and RL95 cells. The SDF-1alpha/CXCL12 concentration in conditioned medium (CM) of UtSMCs(was 4,120 ± 530 pg/ml. Treatments with CM of UtSMCs and plated UtSMCs significantly induced both AMEC and RL95 cell migration. The induced cell migrations were significantly inhibited by CXCR4 mAb (12G5) and CXCR4 antagonist (AMD3100) pre-treatments. Treatments with UtSMCs CM to AMEC and RL95 cells stimulated Akt phosphorylation in a time-dependent manner. Pre-treatment of AMEC and RL95 cells with wortmannin as a PI3K inhibitor significantly inhibited UtSMCs CM-induced cell migration. The SDF-1alpha/CXCL12-CXCR4 chemokine axis between UtSMCs and EMCA played an important role in the muscular infiltration of endometrial cancer through activation of PI3K-Akt signaling pathway. Suppression of this pathway could be an effective target for the treatment of early uterine body cancer in particular.     

Effectiveness of proliferating tissues in combination with bovine-derived xenografts to intrabony defects of alveolar bone in dogs

The aim of this study was to investigate the effect of proliferating tissue used in combination with bovine-derived xenograft (BDX) on the formation of new cementum and bone in dogs. Intrabony defects were treated with either BDX in conjunction with autogenous proliferating tissues (BDXplus-proliferating tissues: BDX-P group) or BDX alone (BDX-alone group). The control group received no BDX or proliferating tissues. The animals were sacrificed after 2, 4, and 8 weeks of the treatment, and tissues were histologically examined. Specimens from the control group were characterized by long junctional epithelium and little bone formation. The BDX-P group showed a statistically significant increase in new bone and cementum formation compared to the BDX-alone group (30.9% vs. 18.7, p < 0.01 and 87.8% vs. 61.8, p < 0.01). The ratio of proliferating cell nuclear antigen (PCNA)-positive cells in the newly formed connective tissue of the BDX-P group was significantly greater than that in the BDX-alone group. These findings suggest that the use of proliferating tissues in combination with BDX enhances new bone and cementum formation, offering potential as therapeutic material in periodontal regeneration.     

Negative association of obesity and its related chronic inflammation with serum glycated albumin but not glycated hemoglobin levels

BACKGROUND: Matrix metalloproteinase-8 (MMP-8) has been implicated in the pathogenesis of cardiovascular disease. We evaluated the relative contribution of genetic and non-genetic variables to serum MMP-8 concentrations in nondiabetic subjects without known cardiovascular disease. METHODS: A blood sample was obtained from 100 subjects > or =18 y. Total serum MMP-8 concentrations were assayed by ELISA. MMP8 genotypes (-799 C/T and -381 A/G) were determined by PCR-pyrosequencing. RESULTS: MMP-8 concentrations were significantly higher in subjects with the metabolic syndrome (n=40) compared to those without the metabolic syndrome (11.71 vs 6.81 ng/ml, p<0.001) and in current smokers compared to non-smokers (13.51 vs 7.53 ng/ml, p=0.001). MMP-8 concentrations were significantly correlated with body mass index, triglyceride/HDL ratio, triglycerides, fasting plasma glucose, and age. MMP-8 concentrations were not significantly different between MMP8 genotype groups. In regression analysis, variables that were significantly associated with serum MMP-8 concentrations were presence of the metabolic syndrome and smoking (p<0.001 and p=0.009, respectively), accounting for 21.4% of the variability in serum MMP-8 concentrations. CONCLUSIONS: Our data demonstrate that the metabolic syndrome and smoking are independently associated with elevated serum MMP-8 concentrations. The relationship between MMP-8 concentrations and cardiovascular risk merits further investigation.     

Quality of life in active surveillance for early prostate cancer

Recently, the prevalence of the prostate-specific antigen screening test for early-stage prostate cancer has increased, but this has also resulted in an increase in insignificant cancers. The treatment outcome of early-stage prostate cancer is excellent, but such a radical treatment also leaves the patient with undesired adverse consequences. To resolve such problems, attention should be paid to active surveillance as a modern treatment option. This study aimed to systematically review the literature about quality of life in prostate cancer patients undergoing active surveillance. Evidence was acquired from PubMed databases in March 2019 using quality of life, prostate cancer, well-being, anxiety, depression, stress, outcomes, active surveillance, radiation therapy and radical prostatectomy as keywords. Five clinical active surveillance studies measured health-related quality of life and related psychological factors, and seven compared active surveillance with other treatments (radical therapy and hormone therapy). Active surveillance was superior to radical therapy for urinary and sexual function. Furthermore, most patients who opted for active surveillance showed lower anxiety and fear of progression, whereas health-related quality of life was maintained. Although active surveillance has the advantage of being non-invasive, its diagnosis and follow-up protocols are unreliable. Because such uncertainty can affect patients’ quality of life, utilization of imaging modalities, such as magnetic resonance imaging, and the development of new biomarkers are required.     

Cumulative probability of prostate cancer detection in biopsy according to free/total PSA ratio in men with total PSA levels of 2.1–10.0 ng/ml at population screening

Purpose

The aim of this study was to investigate the cumulative probability of prostate cancer detection according to free/total prostate-specific antigen (PSA) ratio in men with PSA levels of 2.1–10.0 ng/ml and also likelihood of detecting clinically insignificant prostate cancer in population-based screening.

Methods

A total of 1,277 men aged between 55 and 69 years with total PSA (tPSA) levels of 2.1–10.0 ng/ml screened in population screening in Kanazawa city and underwent systematic transrectal ultrasonography-guided prostate biopsy between 2000 and 2011 were enrolled. The cumulative probability of prostate cancer detection in biopsy according to age, serum tPSA, and free-to-total PSA (f/t PSA) ratio was investigated. The clinicopathological features of screening-detected prostate cancer were also investigated.

Results

Of the 1,277 subjects in the study population, 320 (25.0 %) were diagnosed with prostate cancer during the observation period. The probabilities of prostate cancer detection at 3 years were 64.5, 41.2, 28.5, and 14.3 % for the men with f/t PSA ratio ≤0.08, 0.09–0.13, 0.14–0.22, and ≥0.23, respectively; the differences in probabilities of prostate cancer detection among men with different f/t PSA ratios were statistically significant. Among 320 patients, 84 (26.3 %) had favorable clinicopathological features that made them suitable for active surveillance. The f/t PSA ratio in unfavorable cancer patients was significantly lower that that in favorable cancer patients.

Conclusion

The present study demonstrated that the f/t PSA ratio was a strong predictor of future cancer detection and unfavorable cancerous features in prostate biopsy in men with total PSA levels of 2.1–10.0 ng/ml at population screening.     

Sakuranetin downregulates inducible nitric oxide synthase expression by affecting interleukin-1 receptor and CCAAT/enhancer-binding protein β

Journal of Natural Medicines - Pruni Cortex is a herbal drug from the bark of the Japanese flowering cherries, Prunus jamasakura or Prunus verecunda, and is included in the traditional Japanese...