Treatment of localized‐stage follicular lymphoma

Follicular lymphoma (FL) is the most common indolent lymphoma, and it most frequently presents in an advanced stage. Therapeutic considerations for advanced stage are different from those of localized‐stage FL, in which radiotherapy (RT) is generally recommended. However, the available evidence suffers from shortcomings that are relatively specific to this clinical entity due to its rarity and long survival with all available treatment modalities, including that most of the existing evidence originated at a time when diagnostic classifications, staging procedures and radiotherapeutic standards were different from those available today and when anti‐CD20 monoclonal antibodies were not available. Available treatment modalities include observation, systemic therapy only, RT only and RT in combination with systemic therapy. We review the evidence available with each of them and the data from present‐day clinical practice studies as well as briefly discuss what diagnostic and therapeutic developments may take place in the next few years.     

Huprine X Attenuates The Neurotoxicity Induced by Kainic Acid,Especially Brain Inflammation

Huprine X (HX) is a synthetic anticholinesterasic compound that exerts a potent inhibitory action on acetylcholinesterase (AChE) activity, an agonist effect on cholinergic receptors, neuroprotective activity in different neurotoxicity models in vivo and in vitro and cognition enhancing effects in non‐transgenic (C57BL/6) and transgenic (3xTg‐AD, APPswe) mice. In this study, we assessed the ability of HX (0.8 mg/kg, 21 days) to prevent the damage induced by kainic acid (KA; 28 mg/kg) regarding apoptosis, glia reactivity and neurogenesis in mouse brain. KA administration significantly modified the levels of pAkt1, Bcl2, pGSK3β, p25/p35, increased the glial cell markers and reduced the neurogenesis process. We also observed that pre‐treatment with HX significantly reduced the p25/p35 ratio and increased synaptophysin levels, which suggests a protective effect against apoptosis and an improvement of neuroplasticity. The increase in GFAP (88%) and Iba‐1 (72%) induced by KA was totally prevented by HX pre‐treatment, underlying a relevant anti‐inflammatory action of the anticholinesterasic drug. Our findings highlight the potential of HX, in particular, and of AChEIs, in general, to treat a number of diseases that course with both cognitive deficits and chronic inflammatory processes.     

Cholecystectomy Concomitant with Bariatric Surgery: Safety and Metabolic Effects

Obesity Surgery - Obesity and fast weight loss in the postoperative period of bariatric surgery increase significantly the risk of cholelithiasis. Moreover, emerging evidence has pointed out the...     

Use of prebiotic carbohydrate as wall material on lime essential oil microparticles

The aim of this work was to study the use of different prebiotic biopolymers in lime essential oil microencapsulation. Whey protein isolate, inulin and oligofructose biopolymers were used. The addition of prebiotic biopolymers reduced emulsion viscosity, although it produced larger droplet sizes (0.31–0.32?µm). Moisture values (2.94–3.13?g/100?g dry solids) and water activity (0.152–0.185) were satisfactory, being within the appropriate range for powdered food quality. Total oil content, limonene retention values and antioxidant activity of the microparticles containing essential oil decreased in the presence of the carbohydrates. The addition of prebiotic biopolymers reduced the microparticle thermal stability. X-ray diffraction confirmed the amorphous characteristic of the microparticles and the interaction of the essential oil with the wall material. The presence of prebiotic biopolymers can be a good alternative for lime essential oil microparticles, mainly using fibre that has a functional food appeal and can improve consumer health.     

Salmonella type III-mediated heterologous antigen delivery: a versatile oral vaccination strategy to induce cellular immunity against infectious agents and tumors

Salmonella type III secretion system (T3SS)-mediated translocation can be used for efficient delivery of heterologous antigens to the cytosol of antigen-presenting cells leading to prominent CD8 T-cell priming in orally immunized mice. The time point and duration of hybrid protein translocation during the Salmonella infection cycle can be modulated by employing various type III carrier molecules. The p60 protein of Listeria monocytogenes was used as model antigen to construct chimeric SspH2/p60. SspH2 is a “Salmonella pathogenicity island 2” (SPI2) protein that is known to be translocated by Salmonella during intracellular survival and replication in macrophages. This SPI2 carrier molecule is sufficient to induce a concomitant p60-specific CD4 and CD8 T-cell response in Salmonella-vaccinated mice. Moreover, T3SS-mediated antigen delivery results in an efficient priming of central and effector memory CD8 T cells in spleens of these animals. This vaccination strategy can also be employed to efficiently protect mice from an aggressive fibrosarcoma transfected with p60 in a prophylactic setting.     

Nutritional implications on treatment and recovery of adult patients with chronic diarrhea]

The nutritional assessment by 24 hour-dietary recall, anthropometry and blood-components measurements was undertaken in 23 adult patients, 17 males and 6 females suffering of chronic diarrhea from pancreatitis (30%), inflammatory bowel disease (22%), short intestine syndrome (9%) and unknown diarrhea (35%). The nutritional assessment was done at the entry and repeated at the discharge of the hospitalization that averaged 35 days, during which the patients received specific medical treatment along with obstipating diets. The hospitalization resulted in overall improvement of the patients either clinically by reducing their defecation rate or nutritionally by increasing their protein-energy intake and the values of anthropometry and blood components (albumin, free-tryptophan and lymphocytes). When the patients where divided into two groups based on their fecal-fat output one could note the better nutritional response of the group showing steatorrhea than the non-steatorrhea group, with the serum albumin and the arm-muscle circumference being discriminatory between groups. However even in the better recovered patients the indicative values of a satisfactory nutritional status were not accomplished. Thus, these data suggest that besides the overall nutritional improvement seen in the studied chronic diarrhea patients the full-nutrition recovering would demand either or both a longer hospitalization and/or an early-aggressive nutritional support.     

Binding of 13-amidohuprines to acetylcholinesterase: exploring the ligand-induced conformational change of the gly117-gly118 peptide bond in the oxyanion hole

The acetylcholinesterase (AChE) inhibitory activity of a series of 13-amido derivatives of huprine Y, designed to enlarge the occupancy of the catalytic binding site by mimicking the piridone moiety present in (-)-huperzine A, has been assessed. Although both 13-formamido and 13-methanesulfonamido derivatives are more potent human AChE inhibitors than tacrine and (-)-huperzine A, none of them equals the potency of huprine Y. Molecular modeling studies show that the two derivatives effectively trigger the Gly117-Gly118 conformational flip induced upon binding of (-)-huperzine A, leading to a similar pattern of interactions as that formed by the pyridone amido group of (-)-huperzine A. The detrimental effect on the binding affinity relative to the 13-unsubstituted huprine could be ascribed to a sizable deformation cost associated with the ligand-induced peptide flip. This finding can be interpreted as a mechanism selected by evolution to ensure the preorganization of the functionally relevant oxyanion hole in the binding site of AChE, where residues Gly117 and Gly118 play a relevant role in mediating substrate recognition.     

Use of proteic metabolism (15N-glycine) in the early detection of disease exacerbation in patients with non-specific ulcerative colitis

Disease activity was assessed in 10 (five males and five females) ulcerative colitis patients through the following parameters: clinical, laboratory, sigmoidoscopic and histological. Protein metabolism was also assessed with 15N-glycine and urinary ammonia as end product. Only one patient had exacerbation of the disease two months after the study started. This patient presented in the beginning of the study protein synthesis and breakdown of 4.51 and 3.47 g protein/kg/day, respectively, values higher than all other patients, showing an hypermetabolic state, suggesting an increase of the disease activity. However, this increase was not detected by others indicators and indexes utilized. These data allow to suggest the hypothesis that protein metabolism predicts precociously the exacerbation of disease activity in ulcerative colitis patients.