Brain Glucose-Sensing Mechanism and Energy Homeostasis.

The metabolic and energy state of the organism depends largely on the availability of substrates, such as glucose for ATP production, necessary for maintaining physiological functions. Deregulation in glucose levels leads to the appearance of pathological signs that result in failures in the cardiovascular system and various diseases, such as diabetes, obesity, nephropathy, and neuropathy. Particularly, the brain relies on glucose as fuel for the normal development of neuronal activity. Regions adjacent to the cerebral ventricles, such as the hypothalamus and brainstem, exercise central control in energy homeostasis. These centers house nuclei of neurons whose excitatory activity is sensitive to changes in glucose levels. Determining the different detection mechanisms, the phenotype of neurosecretion, and neural connections involving glucose-sensitive neurons is essential to understanding the response to hypoglycemia through modulation of food intake, thermogenesis, and activation of sympathetic and parasympathetic branches, inducing glucagon and epinephrine secretion and other hypothalamic-pituitary axis-dependent counterregulatory hormones, such as glucocorticoids and growth hormone. The aim of this review focuses on integrating the current understanding of various glucose-sensing mechanisms described in the brain, thereby establishing a relationship between neuroanatomy and control of physiological processes involved in both metabolic and energy balance. This will advance the understanding of increasingly prevalent diseases in the modern world, especially diabetes, and emphasize patterns that regulate and stimulate intake, thermogenesis, and the overall synergistic effect of the neuroendocrine system.

Artificial sweetener saccharin disrupts intestinal epithelial cells' barrier function in vitro.

SCOPE: Consumption of non-nutritive sweeteners (NNS) is a dietary practice used by those who wish to lose weight or by patients on a sugar-restricted diet such as those with DM2. Although these substances are safe, possible biological interactions with the digestive tract, particularly in relation to intestinal permeability, have not been studied. Thus, the current work sought to investigate the action of different NNS on intestinal permeability using an in vitro Caco-2 cell model. METHODS AND RESULTS: Caco-2 cells were incubated with acesulfame K, aspartame, saccharin, or sucralose at equimolar concentrations. Acesulfame K, aspartame, and sucralose did not disrupt monolayer integrity in the cells. However, saccharin increased paracellular permeability and decreased transepithelial electrical resistance (TEER) via a non-cytotoxic mechanism. The levels of the tight junction protein claudin-1 were reduced in Caco-2 cells that had previously been exposed to saccharin. The inhibition of nuclear factor-κB (NF-κB) was able to prevent the reduction in TEER induced by saccharin treatment. Thalidomide, as an inhibitor of ubiquitin ligase, was able to prevent the decrease in claudin-1 protein expression and the TEER reduction in Caco-2 cells. CONCLUSIONS: Saccharin disrupts monolayer integrity and alters paracellular permeability in a Caco-2 cell monolayer model, via a mechanism involving NF-κB activation, resulting in the ubiquitination of the tight junction protein claudin-1. Saccharin consumption may potentially alter the intestinal integrity in humans.

Comparative effect of Phoneutria nigriventer spider venom and capsaicin on the rat paw oedema.

Capsaicin, the pungent component of hot peppers, and the venom of the spider Phoneutria nigriventer are able to activate sensory nerves resulting in cutaneous neurogenic plasma extravasation. This study was undertaken to compare the ability of these substances to evoke oedema in the rat hind-paw and mechanisms underlying this effect. Subplantar injection of either Phoneutria nigriventer venom (PNV; 1-100 microg/paw) or capsaicin (10-200 microg/paw) caused a significant paw oedema that was potentiated by CGRP (10 pmol/paw). In rats treated neonatally with capsaicin to deplete neuropeptides, the paw oedema induced by either PNV (100 microg/paw) or capsaicin (100 microg/paw) was partially reduced (P<0.05). The tachykinin NK1 receptor antagonist SR140333 (0.2 micromol/kg; i.v.) prevented the paw oedema induced by the tachykinin NK1 receptor agonist GR73632 (30 pmol/paw) and partially reduced paw oedema induced by PNV or capsaicin. Treatment of rats with compound 48/80 (5 mg/kg; s.c. 3 days) or with both H1 receptor antagonist (mepyramine; 1 nmol/paw) and 5-HT receptor antagonist (methysergide; 1 nmol/paw) significantly inhibited PNV- or capsaicin-induced paw oedema. The combined treatment with mepyramine and methysergide and SR140333 further reduced PNV- and capsaicin-induced paw oedema. The bradykinin B2 receptor antagonist Hoe 140 affected neither PNV- nor capsaicin-induced responses. Our results suggest that PNV and capsaicin each induce paw oedema that is partially mediated by activation of sensory fibers culminating in the release of substance P as well as by activation of mast cells which in turn release amines such as histamine and 5-HT.

Pharmacological antagonism of Anchietia salutaris extracts on the contraction induced by prostaglandin D2 and U46619 in guinea-pig lung parenchymal strips.

Anchietia salutaris tea is traditionally used in Brazil to treat allergies, suggesting it contains compounds with antagonistic activity on the allergic mediators. We have evaluated extracts and semi-purified fractions of Anchietia salutaris as a source of compounds having this type of antagonism on the contraction induced in guinea-pig lung parenchymal strips and on platelet aggregation and shape change. After 10 min pre-incubation dichloromethane extracts containing 30 or 100 microg mL(-1) inhibited the contraction induced by prostaglandin D2 (PGD2) in guinea-pig lung parenchymal strips with dose ratios (DR) of 0.76+/-0.14 and 0.93+/-0.19, respectively; the amount of inhibition depended both on the concentration and on the time of pre-incubation (DR after 30 min pre-incubation was 1.21+/-0.51). The dichloromethane extract and its semi-purified fractions also inhibited the contractions induced by U46619, a more potent, stable, synthetic agonist of thromboxane A2 (TxA2) prostanoid (TP) receptors, the receptors acted upon by PGD2 to produce lung contractions. The dichloromethane extract did not inhibit the lung parenchymal contractions induced by histamine, leukotriene D4 (LTD4) or platelet-activating factor (PAF). Platelet aggregation induced by U46619, adenosine 5'-diphosphate (ADP) or PAF was not inhibited by the dichloromethane extract. Indeed, the extract potentiated platelet aggregation induced by low concentrations of these agonists and also potentiated the shape change induced by U46619. These results imply that the dichloromethane extract of Anchietia salutaris and its semi-purified fractions contain an active principle that competitively inhibits TxA2 TP receptors, the stimulation of which causes lung parenchymal contraction. The inhibition seems to be selective for this receptor subtype, because the extract fails to inhibit platelet aggregation or shape change. This provides additional support of earlier reports suggesting the occurrence of TP receptor subtypes.

Chemopreventive potential of the tannase-mediated biotransformation of green tea.

Green tea (Camellia sinensis) is one of the most widely consumed beverages in the world. The cancer chemopreventive qualities of green tea have been well documented. Epigallocatechin gallate (EGCG) is often described as the most potently chemopreventive green tea catechin; however, the low bioavailability of EGCG is a limiting factor for its biological effect. Thus, the aim of this work was to test the chemopreventive potential of green tea extract and EGCG after tannase-mediated hydrolysis. The results showed that the biotransformed compounds retained most of the beneficial properties of the original compounds, and some beneficial properties were improved in the biotransformed compounds. Biotransformation of EGCG decreased its toxicity without affecting its antiproliferative effects. Furthermore, human cells gene expression profiling showed that the biotransformed compounds modulated the expression of several genes related to carcinogenesis. These results demonstrate the benefits of the biotechnological modification of natural food molecules, allowing the improvement of the nutraceutical potential of a beverage as green tea.

The inhibitory effects of H+ K+ ATPase inhibitors on human neutrophils in vitro: restoration by a K+ ionophore.

OBJECTIVE: This study investigated the ability of proton pump inhibitors (PPI), such as omeprazole and pantoprazole, to inhibit neutrophil migration, calcium mobilization and the mechanisms involved in this inhibition. METHODS: Neutrophils were incubated with different concentrations of omeprazole and pantoprazole for 30 min and stimulated to migrate with fMLP and IL-8. Treatment toxicity was assessed by MTT assay. The intracellular calcium levels were analyzed in neutrophils pre-treated with omeprazole and pre-loaded with FURA-2AM, when stimulated with fMLP. The activity of p38 MAP Kinase was evaluated by Western blot after treatment with omeprazole. RESULTS: Omeprazole is able to inhibit neutrophil chemotaxis to fMLP and IL-8. Pantoprazole demonstrated the same ability. This inhibitory effect was not due to a toxic effect of the proton pump inhibitors. Inhibition of v-ATPase by bafilomycin did not modify the ability of fMLP or IL-8 to induce neutrophil migration. Omeprazole was also able to decrease intracellular calcium availability. The addition of a potassium ionophore, nigericin, restored the migratory ability, as well as the intracellular calcium levels. The activity of p38 MAP Kinase was decreased in neutrophils pretreated with omeprazole. CONCLUSION: Proton pump inhibitors promote inhibition of H+ K+ ATPase in neutrophils, resulting in cationic flow disturbances through the cellular membrane that, consequently, inhibit migratory and intracellular events such as calcium influx and p38 MAP Kinase activation.

Study of the Adsorption of Some Amino Acids by Silica Chemically Modified with Aminobenzenesulfonic and Phosphate Groups

Two silica gels, one modified with aminobenzenesulfonic (SABS) groups and the other with phosphate (SZP) groups, were prepared to adsorb some amino acids. Chemical analysis of the modified silica gave 0.65 mmol g-1 aminobenzenesulfonic groups and 0.56 mmol g-1 phosphate groups. The maximum adsorption capacities for amino acids determined by batch experiments for SABS were 1.37, 0.67, 0.76, and 0.59 mmol g-1 for glycine, lysine, histidine, and leucine, respectively, and those for SZP were 0.75, 0.58, 0.44, and 0.75 mmol g-1 for glycine, lysine, histidine, and leucine, respectively. The adsorption capacity of SABS was significantly affected by the solution pH, showing a higher selectivity than SZP. The materials were very stable, allowing their use several times without changes in adsorption capacity.

Use of Chemically Modified Silica with beta-Diketoamine Groups for Separation of alpha-Lactoalbumin from Bovine Milk Whey by Affinity Chromatography

Silica gel surface was chemically modified with beta-diketoamine groups by reacting the silanol from the silica surface with 3-aminopropyl-triethoxysilane and 3-bromopentanedione. With this material, copper ions were adsorbed from aqueous solutions. The chemical analysis of the silica-gel-immobilized acetylacetone provided a quantity of 0.67 mmol g-1 of organic groups attached to the support and 0.63 mmol g-1 of copper. This material was used as a stationary phase in IMAC (immobilized metal affinity chromatography), to separate alpha-lactoalbumin from bovine milk whey. The results showed an efficient separation in the chromatographic column. The possibility of reutilization of the stationary phase was also investigated.