Relationship between vitamin D deficiency and cardiovascular disease

Epidemiological studies have found that low 25-hydroxyvitamin D levels may be associated with coronary risk factors and adverse cardiovascular outcomes.Additionally,vitamin D deficiency causes an increase in parathyroid hormone,which increases insulin resistance and is associated with diabetes,hypertension,inflammation,and increased cardiovascular risk.In this review,we analyze the association between vitamin D supplementation and the reduction in cardiovascular disease.The role of vitamin D deficiency in cardiovascular morbidity and mortality is still controversial,and larger scale,randomized placebo controlled trials are needed to investigate whether oral vitamin D supplementation can reduce cardiovascular risk.Given the low cost,safety,and demonstrated benefit of higher 25-hydroxyvitamin D levels,vitamin D supplementation should become a public health priority for combating common and costly chronic cardiovascular diseases.

Insertion Sequence-Dependent <i>OmpK</i>36 Mutation Associated Ertapenem Resistance in Clinical <i>Klebsiella pneumoniae</i>

Extended-spectrum β-lactamases (ESBLs) and/or AmpC enzymes combined with deficiency of porins OmpK35 and OmpK36 are important for the development of carbapenem-resistant Klebsiella pneumoniae. We characterized the clinical K. pneumoniae human isolates and investigated the effect of meropenem induction on the ompK35 and ompK36 mutation to develop carbapenem resistance from six carbapenem-susceptible ESBL-producing K. pneumoniae strains. 163 clinical K. pneumoniae isolates were grouped mostly into the ESBL + AmpC (44.2%) and ESBL (42.9%) phenotypes. The resistance rate differed between cephalosporins (52.1% for cefepime - 97.5% for cefotaxime) and carbapenems (16% for meropenem - 28.2% for imipenem) (P blaTEM, blaSHV, blaCTX-M-3-like, and blaCTX-M-14-like of AmpA β-lactamase genes and blaDHA and blaCMY of AmpC β-lactamase genes. Compared to all 163 clinical isolates, the 56 carbapenem-resistant isolates carried less frequently of blaTEM, blaCTXM-14-like, and blaCTXM-3-like and more frequently of blaDHA-1 and blaCMY-2. The carbapenem-resistant isolates differed in prevalence against imipenem, ertapenem, and meropenem and lacked OmpK35 more frequently than OmpK36, but abnormal PCR amplicons were detected fewer in the Omp K35-deficient group than in the OmpK36-deficient group (32.5% vs. 68.4%, respectively). The carbapenem-resistant isolate mostly carried blaDHA (91.1%) and three isolates carried blaKPC-2. Following induction with meropenem insertion sequences in ompK36, not ompK36, were identified as IS5 for KP08, IS1 for KP15, and IS903 for KP16 isolates. OmpK36 deficiency increased resistance to ertapenem, but not imipenem and meropenem. Clinical isolates belonged mainly to ESBL + AmpC group and ESBL group with difference in resistance to cephalosporins and carbapenems, the bla genes. Carbapenem resistant isolates lacked OmpK35 expression, than the OmpK36 expression, Meropenem induction developed the carbapenem resistant isolates with insertion of different insertion sequences in ompK36, not ompK35.

Significances of Peripheral Inflammatory Cells and Neutrophil/Platelet-Lymphocyte Ratio in Breast Cancer after Resection

Introduction: Breast cancer had become top leading cause of death in Taiwan and endangered women’s health worldwide. Therefore, we try to invest the peripheral inflammatory cell counts and neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) from our routine practice for the predictor of prognosis of breast cancer after resection. Patients and Methods: There were 574 breast cancer patients accepted surgical resection and registered in Cancer Registry Center of our hospital. Patient’s basic profiles, peripheral neutophil, lymphocyte and platelet count were measured for study. The scales of NLR and PLR were derived from the lower and higher normal range in cell count from neutrophil, lymphocyte and platelet respectively. Therefore, the scales for NLR and PLR were ≤1.62, 1.63 - 2.57, ≥2.58 and ≤224, 225 - 253, ≥254 respectively for analysis. Results: Poor 5-yr survival rate was found if higher cell counts of neutrophil and platelet (p ≤ 0.05). Three scales of NLR were ≤1.62, 1.63 - 2.57, ≥2.58, and their 5-year survival rates were 94%, 91% and 84% respectively (p = 0.019). In the subgroup of HER-2 (negative), and 3-Negative breast patients had a higher NLR of poor prognosis. But higher PLR was found less in 3-Negative and non in 3-Positive patients (p = 0.039). The PLR was ≤224, 225 - 253, ≥254 and their 5-year survival rates were 92%, 87%, and 64% respectively (p = 0.001);Multivariate Cox regression model for predictor of breast cancer patients who have 3.39 (PLR ≥ 254) and 2.45 (NLR ≥ 2.58 ) times risk (p = 0.02 and p = 0.002) of poor prognosis respectively. Conclusion: Peripheral inflammatory cell counts are easily to take in our clinical practice and have a potential role as predictors of prognosis. We have to pay attention to the trends of peripheral inflammatory cell count and their ratio in our clinical practice where possible.

Role of Pre-Operative of Neutrophil/Lymphocyte and Platelet/Lymphocyte Ratio in Prognosis of Hepatocellular Carcinoma

Introduction: Hepatocellular carcinoma (HCC) has a poor prognosis and is ranked in the top 2 leading causes of death in Taiwan. The clinical features which affect survival rate should be noticed for alarming. We tried to study the neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) for the predictor of prognosis of HCC. Patients and Methods: A total of 525 patients with HCC were undergone surgical or non-surgical treatment registered in Cancer Registry Center of our hospital. The clinical features included patient’s basic profiles, and neutrophil, lymphocyte and platelet count in the peripheral blood at the time of diagnosis. The ratio of neutrophil/lymphocyte and platelate/lymphocyte was measured and their survival rates were analyzed based on their ratio scales. Results: Three scales of NLR and PLR were ≤1.62, 1.63 - 2.57, ≥2.58 and ≤224, 225 - 253, ≥254 respectively. Either higher NLR ≥ 2.58 or higher PLR ≥ 254 was found mostly in the male and TMN stage III and IV with a significant difference (P < 0.01). The 5-year survival rates of NLR ≤ 1.62, 1.63 - 2.57, ≥2.58 were 33.9%, 33.7%, and 16.7% respectively (P < 0.001). The mean survival times were 34.1 ± 1.4, 29.3 ± 8.1, and 14.2 ± 2.1 months for the scales of PLR ≤ 224, 225 - 253, and ≥ 254 respectively. The 5-year survival rates were 25.5%, 36.4%, and 7.7% for the groups of the PLR ≤ 224, 225 - 253, and ≥254 respectively (p < 0.001). Conclusion: Neutrophil, lymphocyte and platelet are players in cancer growth and have a potential role as predictors of survival in our HCC patients. Therefore, we should pay more attention to the higher NLR or PLR which will result in a poorer prognosis in our patients.

Constitutive Overexpression of Bcl-2, Survivin and ER Stress Chaperone GRP-78 Confers Intrinsic Radioresistance in Human Hepatocellular Carcinoma Cells: Insight into the Mechanistic Pathways Involved

We present evidence here that abundantly expressed b-catenin-triggered NF-kB-dependent upregulation of inducible nitric oxide synthase(iNOS) found in hepatoma Mahlavu cells (RT-resistant variant designated as RR-Mal), but not in Hep 3B cells (RT-sensitive variant designated as RS-3B) is a key element contribrting to the radioresisitance through the activation of two prominent radioprotective pathways. First, high iNOS expression found in RR-Mal, but not in RS-3B cells was found to perturb calcium homeostasis that triggered ER stress response leading to the overproduction of ER chaperone GRP-78 via robust generation of cleaved ATF-6a (50 kDa) subunits and their nuclear translocation. Meanwhile, both abundantly expressed NF-κB and COX-2 found in RR-Mal cells could also provoke an increased production of PGE2 resulting in robust production of Bcl-2. Interestingly, when RR-Mal cells were treated with PDTC (a NF-κB inhibitor) or celecoxib (a COX-2 inhibitor), a concentration-dependent downregulation of Bcl-2 could be demonstrated implying that Bcl-2 overexpression was indeed mediated through NF-κB/Cox-2/PGE2 pathway. Importantly, we also unveiled that siRNA-mediated silencing of survivin in RR-Mal cells could result in a concomitant downregulation of GRP-78 due to a severe inhibition of ATF-6a (50 kDa) expression. Taken together, our data demonstrate that constitutively overexpressed b-catenin/NF-κB/iNOS and NF-κB/COX-2/PGE2 pathways that overproducing GRP-78, survivin and Bcl-2 expressions are responsible for radioresistance acquisition in RR-Mal cells. Thus, both pathways could be served as potential targets for overcoming radioresistance.