Downregulation of Prlr gene expression in the duodenum may explain the diminished intestinal calcium absorption in medicamentous hyperprolactinaemia. Prolactin takes calcium from the skeletal system following increased Prlr gene expression in the vertebrae to maintain calcium homeostasis, which increases the harmful effect on bone metabolism compared to that of physiological hyperprolactinaemia.

Objective The present study aimed to investigate the metabolic activity and adherence capacity of the whole bone marrow cell (wBMC) population and changes in bone marrow (BM) architecture after acute pancreatitis (AP) induction. Methods The disease was induced by injecting L-arginine (350 mg/100 g; i.p.). The control animals, animals injected with L-arginine, and animals pre-treated with allopurinol were included in this study. Serum and routine pathohistological analysis were conducted to confirm the induction of AP. The metabolic activity and adherence capacity of wBMC were evaluated in the MTT assay and methylene-blue test, respectively, and the alterations in pancreatic tissue and BM were examined on histological sections. In addition, immunohistochemical expression of β-catenin was assessed in the pancreatic tissue. Results The wBMC adherence capacity and their total number significantly increased after AP induction. The adherence capability of wBMC was reduced in rats pre-treated with allopurinol. There were no statistically significant changes in the metabolic activity of wBMCs. In the BM isolated from AP and allopurinol pre-treated animals, a discrete left shift in granulocytopoiesis was found, with a slight increase in the myeloid-to-erythroid ratio. Conclusions After AP induction, it was shown that wBMCs expressed increased adherence capacity and unchanged metabolic activity, while the alterations in BM may reflect the general activation of myelopoiesis, which would agree with the increased mobilization of mesenchymal stem cells. Also, a significant decrease in β-catenin expression in the pancreatic tissue was noticed.

Introduction: Despite the important role of general KRAS mutational status in the selection of an adequate therapeutic protocol in patients with colorectal cancer (CRC), studies that focus on its specific mutations and their significance on progression of disease are scarce. This study aimed to determine the significance of specific KRAS mutations in response to standard chemotherapy protocols with oxaliplatin-based (FOLFOX 4, OXFL) in the first-line and irinotecan-based chemotherapy (FOLFIRI, IFL) in the second-line therapy, and to evaluate the correlation between these mutations and clinicopathological characteristics of CRC patients. Methods: Genomic DNA was extracted from the FFPE tumour tissue sections while the KRAS mutation test was performed by using PCR methods. Results: Prevalence of KRAS gene mutations in CRC patients was 45%. Mutated KRAS was more frequent in later stages of tumor infiltrations (P =0.0017), on the right side of the colon (P= 0.0044), and in patients who developed metastases in the first 6 months after CRC diagnosis than in patients who developed metastases after 24 months (P=0.0083). In a group of patients with a poor therapeutic response to standard chemotherapy the most frequent mutations in KRAS gene were G12D and G12V (63.88%), while in a group of patients with a good response to therapeutic protocols the most prevalent mutation was G12A (66.66%). Conclusion: Our results indicate that there was a significant difference in biological behaviour between tumours harboring different mutations in KRAS gene. Overall, mutation G12A could be a novel prognostic biomarker for CRC patients treated with standard chemotherapy.

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