A pilot study of blood epinephrine levels and CREB phosphorylation in men undergoing prostate biopsies

Purpose

In mouse models of prostate cancer, increased epinephrine levels accelerated tumor growth via the beta2-adrenoreceptor/PKA signaling pathway. It is unknown, however, whether men experience increased epinephrine levels sufficient to activate the beta2-adrenoreceptor/PKA pathway in the prostate gland. We measured epinephrine levels in blood samples collected immediately prior to prostate biopsies and measured phosphorylation of S133CREB (PKA site), S112BAD, T202/Y204ERK, and S473 Akt in prostate biopsy tissue samples.

Methods

Tissue samples and 3 ml of blood were obtained from men (n = 20) recruited from the patients scheduled for prostate biopsies. Epinephrine levels were measured by ELISA. Proteins were extracted from biopsied tissue, and protein phosphorylation was measured by Western blotting with phospho-specific antibodies. Pearson and Spearman’s rank correlations were analyzed to assess relationships between blood epinephrine levels and phosphorylation of CREB, BAD, AKT, and ERK.

Results

Epinephrine levels above 1 nM were detected in 5 of 20 patients. A strong positive correlation was observed between increased epinephrine levels and CREB phosphorylation. In contrast, no correlation was observed between epinephrine levels and phosphorylation of ERK, BAD, or AKT.

Conclusion

Our results suggest that increased blood epinephrine levels activate the beta2-adrenoreceptor/PKA signaling pathway in human prostate glands. These results will inform future studies to examine whether beta2-selective blockers can inhibit activation of the epinephrine/ADRB2/PKA pathway in prostate tumors of men with increased epinephrine levels and explore the use of beta2-selective blockers as adjuvant therapy for prostate cancer.     

The ringed esophagus

Abdominal Radiology -     

Accuracy of a predictive model for severe hepatic fibrosis or cirrhosis in chronic hepatitis C

AIM: To assess the accuracy of a model in diagnosing severe fibrosis/cirrhosis in chronic hepatitis C virus (HCV) infection. METHODS: The model, based on the sequential combination of the Bonacini score (BS: ALT/AST ratio, platelet count and INR) and ultrasonography liver surface characteristics, was applied to 176 patients with chronic HCV infection. Assuming a pre-test probability of 35%, the model defined four levels of post-test probability of severe fibrosis/cirrhosis: <10% (low), 10-74% (not diagnostic), 75-90% (high) and >90% (almost absolute). The predicted probabilities were compared with the observed patients' distribution according to the histology (METAVIR). RESULTS: Severe fibrosis/cirrhosis was found in 67 patients (38%). The model discriminated patients in three comparable groups: 34% with a very high (>90%) or low (<10%) probability of severe fibrosis, 33% with a probability ranging from 75% to 90%, and 33% with an uncertain diagnosis (i.e., a probability ranging from 10% to 74%). The observed frequency of severe fibrosis/ cirrhosis was within the predefined ranges. CONCLUSION: The model can correctly identify 67% of patients with a high (>75%) or low (<10%) probability of cirrhosis, leaving only 33% of the patients still requiring liver biopsy.     

Mental health conditions and the risk of chronic opioid therapy among patients with rheumatoid arthritis: a retrospective veterans affairs cohort study

Clinical Rheumatology - Patients with rheumatoid arthritis (RA) often receive opioid analgesics for pain management. We examined the association between mental health conditions and the risk of...     

Cod Liver Oil,but Not Retinoic Acid,Treatment Restores Bone Thickness in a Vitamin A-Deficient Rat

Vitamin A plays a prominent role for maintaining optimal bone status, but its impact upon the bone in response to vitamin A deficiency is not well defined. The purpose of this study was to evaluate how replenishing vitamin A by either whole food cod liver oil (COD) or the active metabolite of vitamin A, retinoic acid (RA), altered bone thickness of vitamin A-deficient (VAD) rats. Weanling rats were administered a control diet (CTRL) or VAD diet for 9 weeks. This was followed by four weeks of treatment in which the VAD group was divided into the following 4 subgroups: (1) VAD (9 weeks)-VAD (4 weeks); (2) VAD-CTRL; (3) VAD-COD; and (4) VAD-RA. Compared to controls, VAD rats had thicker bones which showed marked dysplasia. VAD-rats treated with COD produced a thinner bone that was not significantly different from that of untreated rats. In contrast, RA did not significantly change the thicker bone, and also had significantly greater periosteal and endosteal osteoblast numbers compared to VAD-COD. Active osteoclasts were not detected in VAD rats, nor during the treatment period. These findings suggest that the abnormal bone thickness in VAD rats appears to be more effectively restored to bone thickness of untreated control rats when treated with COD.     

Human breast milk exosomes attenuate intestinal damage

Pediatric Surgery International - Human breast milk (HBM), which contains an abundant supply of exosomes, is known to prevent necrotizing enterocolitis (NEC). Preterm infants are commonly given...     

Monitoring carcinoembryonic antigen in colorectal cancer: Is it still useful?

The results of a study conducted to determine the usefulness of carcinoembryonic antigen (CEA) monitoring in the follow-up of patients with resected colorectal cancer are reported herein. The subjects of this study were 125 patients in whom CEA had been determined preoperatively and 239 patients in whom CEA had been monitored postoperatively. The results revealed increased preoperative CEA in only 24% of the subjects, and that this increment was correlated with subsequent more advanced tumor stage and a higher recurrence rate (P<0.01). The postoperative CEA level exceeded the threshold in 71% of the patients affected by recurrence, 94.4% of whom developed liver metastases and 50%, nonhepatic recurrence. This marker showed elevated sensitivity for liver metastases (99%), whereas the sensitivity was lower for nonhepatic recurrence of the disease (94%). Thus, we concluded that CEA monitoring can be useful for preoperative colorectal tumor grading, even if its validity in the early diagnosis of recurrence is problematic, especially in terms of radical repeated surgery and survival.