Background: Obesity increases the risk of coronary heart disease, partly due to its strong association with atherogenic dyslipidemia, characterized by high triglycerides and low high-density lipoprotein (HDL) cholesterol levels. Functional impairment of HDL may contribute to the increased cardiovascular mortality, but the effect of obesity on composition, structure, and function of HDL is not well understood. Design and Methods: We determined HDL composition, HDL subclass distribution, parameters of HDL function, and activities of most important enzymes involved in lipoprotein remodeling, including lecithin–cholesterol acyltransferase (LCAT) and cholesteryl ester transfer protein (CETP) in relatively young normal weight (n = 26), overweight (n = 22), and obese (n = 20) women. Results: Obesity (body mass index (BMI) ≥ 30) was associated with noticeable changes in LCAT and CETP activities and altered HDL composition, such as decreased apolipoprotein A-I, cholesterol, and phospholipid content, while pro-inflammatory HDL serum amyloid a content was increased. We observed a marked shift towards smaller HDL subclasses in obesity linked to lower anti-oxidative capacity of serum. LCAT activity, HDL subclass distribution, and HDL-cholesterol were associated with soluble leptin receptor, adiponectin, and liver enzyme activities. Of note, most of these alterations were only seen in obese women but not in overweight women. Conclusions: Obesity markedly affects HDL metabolism, composition, and subclass distribution linked to changes in liver and adipose tissue. HDL dysfunction may contribute to increased cardiovascular risk in obesity.

Single and/or combined food intolerance/malabsorption may cause nonspecific, functional gastrointestinal (GI) complaints. In lactose-intolerant patients we evaluated the influence of additional food intolerance/malabsorption with hydrogen (H2) breath tests. In a retrospective analysis of charts from 279 lactose-intolerant patients, we found 128 patients with only lactose intolerance (LIT). Then, we identified 106 LIT patients with additional histamine intolerance (HIT). Additionally, 45 LIT and HIT patients also had fructose malabsorption (FM). A hydrogen (H2) breath test was performed to evaluate LIT and FM. A serum diamine oxidase value of <10 U/mL and a response to a histamine-reduced diet was used to identify HIT. Using pairwise comparison with the Kruskal–Wallis test to associate the area under the curve (AUC) of LIT patients and, LIT with HIT, to LIT with HIT and FM it was found, that the exhaled hydrogen values were significantly higher in patients with two-fold and triple combined food intolerance/malabsorption (p < 0.004 and p < 0.001, respectively). Within the pool of 170 LIT patients with >20 ppm increase of expiratory H2 from baseline, there were 74 LIT-only patients, 60 LIT with HIT patients, and 36 LIT patients with additional HIT and FM. With the Kruskal–Wallis test AUCs demonstrated a significant difference between all three groups (p = 0.024). In patients with LIT, the presence of additional food intolerance/malabsorption, significantly increases expiratory H2 values. We demonstrate evidence, which may suggest HIT to embody an own GI disorder as food intolerance/malabsorption.

Bipolar Disorder (BD) is characterized by recurring mood swings, which are not completely understood yet. So far, it is an accepted theory that multiple factors contribute to pathogenesis of BD according to the vulnerability-stressmodel. This model combines on the one hand biological predisposing vulnerability, and on the other hand several chronic and acute stressful negative events as underlying mechanisms of BD. Recently, ER (Endoplasmic Reticulum) stress reached the spotlight of BD research again. The expression of the chaperone BiP (syn. GRP78/glucose-regulated protein, 78kDa), which is highly expressed in the Endoplasmic Reticulum (ER), is upregulated by different kinds of mood stabilizers. These results implied that the ER, an organelle which is prone towards different kinds of cellular stress, might be involved in the pathophysiology of BD. This hypothesis was further strengthened by hypothesis driven genetic association studies, which showed significant association of BiP promotor polymorphisms with BD. Also other ER-stress associated genes like XBP1 (X-box binding protein 1) or GRP94 (glucose-regulated protein, 94kDa, synonym for heat shock protein HSP90B1) were recently linked to BD in hypothesis driven gene association studies. In addition to the proteins mentioned before, our review focuses on further UPR (Unfolded Protein Response) related proteins associated with BD and raises the hypothesis that ER-stress may represent a common interface between BD and obesity which is overrepresented in BD patients. Finally, members of the UPR pathway are discussed as putative targets for mood stabilizers.

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Medullary thyroid carcinoma (MTC) originates from the C-cells of the thyroid and is not sensitive to radiation or chemotherapy. Therefore, surgical removal of the tumor tissue in its entirety is the only curative treatment for MTC. The present study aimed to examine the potential mechanisms of action of extracts of Trailliaedoxa gracilis (TG; WW Smith & Forrest), a plant from the province of Sichuan, China, and of ursolic acid (UA), a pentacyclic triterpen present in TG, on the MTC-SK MTC cell line. A total of 13 TG fractions and UA were examined in vitro for their effects on cell morphology, cell number, proliferation and rates of apoptosis. Reverse transcription-quantitative polymerase chain reaction of nuclear factor-κB essential modifier (NEMO) was performed to delineate the role of the apoptotic pathway following treatment with UA. TG and UA were examined in vivo in xenotransplanted MTC-bearing severe combined immunodeficient mice. The TG fractions exhibited antiproliferative effects, with inhibition of mitochondrial activity in the tumor cells at concentrations, which caused no impairment of the normal control cells. The apoptotic rates of the MTC-SK cells treated with the TG fractions and UA were determined, in which no marked tumor inhibition was observed in the treated MTC-mice, and no change in the expression of NEMO was detected in the treated MTC-SK cells. The observation of early-onset activation of caspase 8 suggested that the responsible factor was linked to NEMO, an anti-apoptotic protein. However, no differences in the mRNA transcription levels of NEMO were detected in MTC-SK cells treated with UA, suggesting that this protein was not associated with the signal transducer and activator of transcription 3 pathway.