The influence of laparoscopic adjustable gastric banding and laparoscopic sleeve gastrectomy on weight loss, plasma ghrelin, insulin, glucose and lipids

The aim of this study was to assess the impact of laparoscopic gastric banding and laparoscopic sleeve gastrectomy on the concentration of ghrelin, insulin, glucose, triglycerides, total and HDL-cholesterol, as well as AST and ALT levels in plasma in patients with obesity. The research includes 200 patients operated using LAGB (34 men average age 37.0 ± 12.6 years and 66 women average age 39.18 ± 12.17 years) and LSG (48 men average age 47.93 ± 9.24 years and 52 women, 19 ± 9.33 years). The percentage of effective weight loss, effective BMI loss, concentration of ghrelin, insulin, glucose, triglycerides, total cholesterol, HDL-cholesterol, LDL-cholesterol, ALT, AST and HOMA IR values was taken preoperatively and at 7th day, 1 month, 3 and 6 months after surgery. Both after LSG and after LAGB, statistically significant reduction in BMI, serum insulin, glucose and HOMA IR was noticed in comparison to the preoperative values. Post LAGB, patients showed an increase of ghrelin, while LSG proved ghrelin decreased. Correlations between glucose and BMI loss, and between insulin and BMI loss in both cases are more favorable in the LSG group. Lipid parameters, AST and ALT have undergone declines or increases in the particular time points. Both techniques cause weight loss and this way lead to changes in the concentration of ghrelin, as well as to the improvement of insulin, glucose, cholesterol and triglycerides metabolism. They reduce metabolic syndrome and multiple comorbidities of obesity.     

Comparison of CD15, galectin-3 and HBME-1 expression in follicular thyroid neoplasms

INTRODUCTION: Estimation of malignancy in thyroid follicular neoplasms is a common diagnostic problem, thus revealing of differences in expression of some antigens in both benign and malignant lesions seems to be essential. The aim of this study is to evaluate the immunohistochemical expression of CD15, galectin-3 and HBME-1 in follicular adenomas and carcinomas. MATERIAL AND METHODS: Samples of 38 follicular adenomas (23 "classical", 5 with intracapsular invasion, 10 oncocytic) and 15 follicular carcinomas (9 "classic", 6 oncocytic) were stained immunohistochemically with anti-CD15, galectin-3 and HBME-1. RESULTS: In the whole group we found statistically significant differences in CD15 expression between follicular adenomas and carcinomas. "Classic" follicular carcinomas (without oncocytic tumors) showed stronger CD15 and HBME- 1 expression than "classic" adenomas. Adenomas with intracapsular invasion differed from "classic" adenomas only in HBME-1 expression. In oncocytic tumors the expression of examined antigens was similar. CONCLUSIONS: 1. In the group of nonoxyphilic tumors positive reaction with HBME-1 was more common in adenomas with intracapsular invasion and carcinomas, but positive reaction with anti-CD15--only in carcinomas. We suggest that reactivity with these antibodies could mark malignancy. 2. Oncocytic tumors had similar expression of CD15 and HBME-1 and galectin-3.     

Cytotoxic and proapoptotic activity of diterpenoids from in vitro cultivated Salvia sclarea roots. Studies on the leukemia cell lines

Four diterpenoids, ferruginol, salvipisone, aethiopinone and 1-oxoaethiopinone, were isolated from transformed roots of Salvia sclarea. Salvipisone and aethiopinone showed relatively high cytotoxicity against HL-60 and NALM-6 leukemia cells (IC50 range 0.6-7.7 microg/ mL which is equal to 2.0-24.7 microM), whereas 1-oxoaethiopinone and ferruginol were less active in this regard. Moreover, we have found that all four diterpenoids of S. sclarea had equal cytotoxic activity against parental HL-60 and multidrug-resistant HL-60 ADR cells, what indicates that they are poor substrates for transport by multidrug resistance-associated protein (MRP1). Caspase-3 activity determinations showed that salvipisone and aethiopinone were able to induce apoptosis in a time- and concentration-dependent manner. The results obtained in this study show that S. sclarea diterpenoids aethiopinone and salvipisone may be useful in the treatment of human cancers, especially in the case of drug resistance.     

Variants of human thymidylate synthase with loop 181–197 stabilized in the inactive conformation

Loop 181–197 of human thymidylate synthase (hTS) populates two major conformations, essentially corresponding to the loop flipped by 180°. In one of the conformations, the catalytic Cys195 residue lies distant from the active site making the enzyme inactive. Ligands stabilizing this inactive conformation may function as allosteric inhibitors. To facilitate the search for such inhibitors, we have expressed and characterized several mutants designed to shift the equilibrium toward the inactive conformer. In most cases, the catalytic efficiency of the mutants was only somewhat impaired with values of k_cat/K_m reduced by factors in a 2–12 range. One of the mutants, M190K, is however unique in having the value of k_cat/K_m smaller by a factor of ～7500 than the wild type. The crystal structure of this mutant is similar to that of the wt hTS with loop 181–197 in the inactive conformation. However, the direct vicinity of the mutation, residues 188–194 of this loop, assumes a different conformation with the positions of C_α shifted up to 7.2 Å. This affects region 116–128, which became ordered in M190K while it is disordered in wt. The conformation of 116–128 is however different than that observed in hTS in the active conformation. The side chain of Lys190 does not form contacts and is in solvent region. The very low activity of M190K as compared to another mutant with a charged residue in this position, M190E, suggests that the protein is trapped in an inactive state that does not equilibrate easily with the active conformer.     

Signaling from endosomes: location makes a difference

In all transmembrane receptor systems the kinetics of receptor trafficking upon ligand stimulation is maintained in a balance between degradative and recycling pathways in order to keep homeostasis and to strictly control receptor-mediated signaling. Endocytosis is commonly considered as an efficient mechanism of uptake and transport of membrane-associated signaling molecules leading to attenuation of ligand-induced responses. Accumulating evidence, however, shows that signaling from internalized receptors not only continues in endosomal compartments, but that there are also distinct signaling events that require endocytosis. Endocytic organelles form a dynamic network of subcellular compartments, which actively control the timing, amplitude, and specificity of signaling. In this review we provide examples in which signal transduction either requires an active endocytic machinery, or directly originates from various types of endosomes. Based on recent discoveries, we emphasize the close interdependence between signaling and endocytosis, and the physiological relevance of endocytic transport in health and disease.