Association of serum adipocytokine levels with cardiac autonomic neuropathy in type 2 diabetic patients

<p>Abstract</p> <p>Background</p> <p>Cardiac autonomic neuropathy (CAN) is a common complication of diabetes associated with poor prognosis. In addition, the autonomic imbalance is associated with cardiovascular disease (CVD) in diabetes. It is thought that adipocytokines contribute to the increased risk of vascular complications in patients with type 2 diabetes mellitus (T2DM). However, literature data on the association between CAN with adipocytokines such as leptin, tumor necrosis factor-alpha (TNF-alpha), adiponectin in subjects with T2DM is limited.</p> <p>Therefore, in the present study, we examined the relationship between fasting serum leptin, TNF- alpha and adiponectin and CAN in Korean T2DM patients.</p> <p>Methods</p> <p>A total of 142 T2DM patients (94 males, 48 females) were recruited. CAN was assessed by the five tests according to the Ewing's protocol and the time and frequency domain of the heart rate variability (HRV) was evaluated. Serum TNF-alpha and adiponectin levels were measured using enzyme-linked immunosorbent assay and serum leptin levels were measured using radioimmunoassay.</p> <p>Results</p> <p>Although, the mean levels of leptin, TNF-alpha and adiponectin were not significantly different between the groups with and without CAN, the levels of leptin and adiponectin had a tendency to increase as the score of CAN increased (p = 0.05, p = 0.036). Serum leptin levels demonstrated a negative correlation with low frequency (LF) in the upright position (p = 0.037). Regarding TNF-alpha, a significant negative correlation was observed with SDNN and RMSSD in the upright position (p = 0.023, p = 0.019). Adiponectin levels were not related to any HRV parameters. Multivariate logistic regression analysis demonstrated that the odds of CAN increased with a longer duration of diabetes (1.25, [1.07-1.47]) and higher homeostatic model of assessment-insulin resistance (HOMA-IR) (5.47, [1.8-16.5]). The relative risks for the presence of CAN were 14.1 and 51.6 for the adiponectin 2^nd, 3^rdtertiles when compared with first tertile (p-value for trend = 0.022).</p> <p>Conclusions</p> <p>In the present study, the higher serum adiponectin levels and HOMA-IR were associated with an increased risk for the presence of CAN. Also, the CAN score correlated with the serum adiponectin. Serum adipocytokines such as leptin and TNF-alpha were significantly correlated with parameters of HRV, representative markers of CAN. Future prospective studies with larger number of patients are required to establish a direct relationship between plasma adipocytokine concentrations and the development or severity of CAN.</p

Unleashing the full potential of Hsp90 inhibitors as cancer therapeutics through simultaneous inactivation of Hsp90, Grp94, and TRAP1

Cancer therapeutics: Extending a drug&apos;s reach A new drug that blocks heat shock proteins (HSPs), helper proteins that are co-opted by cancer cells to promote tumor growth, shows promise for cancer treatment. Several drugs have targeted HSPs, since cancer cells are known to hijack these helper proteins to shield themselves from destruction by the body. However, the drugs have had limited success. Hye-Kyung Park and Byoung Heon Kang at Ulsan National Institutes of Science and Technology in South Korea and coworkers noticed that the drugs were not absorbed into mitochondria, a key cellular compartment, and HSPs in this compartment were therefore not being blocked. They identified a new HSP inhibitor that can reach every cellular compartment and inhibit all HSPs. Testing in mice showed that this inhibitor effectively triggered death of tumor cells, and therefore shows promise for anti-cancer therapy. The Hsp90 family proteins Hsp90, Grp94, and TRAP1 are present in the cell cytoplasm, endoplasmic reticulum, and mitochondria, respectively; all play important roles in tumorigenesis by regulating protein homeostasis in response to stress. Thus, simultaneous inhibition of all Hsp90 paralogs is a reasonable strategy for cancer therapy. However, since the existing pan-Hsp90 inhibitor does not accumulate in mitochondria, the potential anticancer activity of pan-Hsp90 inhibition has not yet been fully examined in vivo. Analysis of The Cancer Genome Atlas database revealed that all Hsp90 paralogs were upregulated in prostate cancer. Inactivation of all Hsp90 paralogs induced mitochondrial dysfunction, increased cytosolic calcium, and activated calcineurin. Active calcineurin blocked prosurvival heat shock responses upon Hsp90 inhibition by preventing nuclear translocation of HSF1. The purine scaffold derivative DN401 inhibited all Hsp90 paralogs simultaneously and showed stronger anticancer activity than other Hsp90 inhibitors. Pan-Hsp90 inhibition increased cytotoxicity and suppressed mechanisms that protect cancer cells, suggesting that it is a feasible strategy for the development of potent anticancer drugs. The mitochondria-permeable drug DN401 is a newly identified in vivo pan-Hsp90 inhibitor with potent anticancer activity

Choledochal cyst with ectopic distal location of the papilla of Vater

In cholangiographic techniques, the close relationship between choledochal cyst and anomalous union of pancreaticobiliary duct has attracted medical attention. There have been rare cases in which the papilla of Vater was found in a position other than its normal position, and such cases have been reported sporadically. However, such cases are interesting in the anatomical context. In this review, we present our experience of choledochal cyst in a 30-month-old boy in whom the papilla of Vater was positioned in the third portion of the duodenum

Homeobox gene Dlx-2 is implicated in metabolic stress-induced necrosis

<p>Abstract</p> <p>Background</p> <p>In contrast to tumor-suppressive apoptosis and autophagic cell death, necrosis promotes tumor progression by releasing the pro-inflammatory and tumor-promoting cytokine high mobility group box 1 (HMGB1), and its presence in tumor patients is associated with poor prognosis. Thus, necrosis has important clinical implications in tumor development; however, its molecular mechanism remains poorly understood.</p> <p>Results</p> <p>In the present study, we show that Distal-less 2 (Dlx-2), a homeobox gene of the Dlx family that is involved in embryonic development, is induced in cancer cell lines dependently of reactive oxygen species (ROS) in response to glucose deprivation (GD), one of the metabolic stresses occurring in solid tumors. Increased Dlx-2 expression was also detected in the inner regions, which experience metabolic stress, of human tumors and of a multicellular tumor spheroid, an <it>in vitro </it>model of solid tumors. Dlx-2 short hairpin RNA (shRNA) inhibited metabolic stress-induced increase in propidium iodide-positive cell population and HMGB1 and lactate dehydrogenase (LDH) release, indicating the important role(s) of Dlx-2 in metabolic stress-induced necrosis. Dlx-2 shRNA appeared to exert its anti-necrotic effects by preventing metabolic stress-induced increases in mitochondrial ROS, which are responsible for triggering necrosis.</p> <p>Conclusions</p> <p>These results suggest that Dlx-2 may be involved in tumor progression via the regulation of metabolic stress-induced necrosis.</p

Antiosteoporosis Activity of New Oriental Medicine Preparation (Kyungokgo Mixed with Water Extract of Hovenia dulcis

Protective effect of new oriental medicine (Kyungokgo mixed with water extract of Hovenia dulcis, KOGHD) was assessed on the bone loss induced mice by ovariectomy. In the in vivo experiments, antiosteoporosis effect of KOGHD was investigated using ovariectomized osteoporosis mice model. After 6 weeks of treatment, the mice were euthanized, and the effect of Kyungokgo (KOG) and KOGHD on body weight, spleen weigh, thymus weight, uterine weight, serum biochemical indicators, bone weight and length, immune cell population, bone morphometric parameters, and histological stains was observed. Our results showed that KOGHD prevented the deterioration of trabecular microarchitecture caused by ovariectomy, which were accompanied by the lower levels of bone turnover markers and immune cell population as evidenced by the inhibition of RANKL-mediated osteoclast differentiation without cytotoxic effect on bone marrow derived macrophages (BMMs). Therefore, these results suggest that the Hovenia dulcis (HD) supplementation in the KOG may also prevent and treat bone loss

Brucellosis among ruminants in some districts of Bangladesh using four conventional serological assays

Brucellosis causes a great economic loss to the livestock industries through abortion, infertility, birth of weak and dead offspring, increased calving interval and reduction of milk yield and it is endemic in Bangladesh. The present study was performed to know the seroprevalence of brucellosis for 1000 ruminants (135 Buffaloes, 465 cattle, 230 goats and 170 sheep) in five different districts of Bangladesh by four conventional serological tests such as: Rose Bengal Plate Test (RBT), tube agglutination test (TAT), competitive enzyme-linked immunosorbent assay (C-ELISA), and Fluorescent polarization assay (FPA). Sheep has the highest prevalence (8.24%) of brucellosis. The seroprevalence of brucellosis was significantly higher in animals with previous abortion record in case of buffaloes, cattle, goats and sheep than that with no abortion record. C-ELISA can be the most suitable choice for extensive use in many kinds of livestocks and accurate estimation of Brucella antibodies in ruminants in Bangladesh