Taste of Fat: A Sixth Taste Modality?

An attraction for palatable foods rich in lipids is shared by rodents and humans. Over the last decade, the mechanisms responsible for this specific eating behavior have been actively studied, and compelling evidence implicates a taste component in the orosensory detection of dietary lipids [i.e., long-chain fatty acids (LCFA)], in addition to textural, olfactory, and postingestive cues. The interactions between LCFA and specific receptors in taste bud cells (TBC) elicit physiological changes that affect both food intake and digestive functions. After a short overview of the gustatory pathway, this review brings together the key findings consistent with the existence of a sixth taste modality devoted to the perception of lipids. The main steps leading to this new paradigm (i.e., chemoreception of LCFA in TBC, cell signaling cascade, transfer of lipid signals throughout the gustatory nervous pathway, and their physiological consequences) will be critically analyzed. The limitations to this concept will also be discussed in the light of our current knowledge of the sense of taste. Finally, we will analyze the recent literature on obesity-related dysfunctions in the orosensory detection of lipids ("fatty" taste?), in relation to the overconsumption of fat-rich foods and the associated health risks.

A new diversity index.

We introduce here a new index of diversity based on consideration of reasonable propositions that such an index should have in order to represent diversity. The behaviour of the index is compared with that of the Gini-Simpson diversity index, and is found to predict more realistic values of diversity for small communities, in particular when each species is equally represented and for small communities. The index correctly provides a measure of true diversity that is equal to the species richness across all values of species and organism numbers when all species are equally represented, as well as Hill's more stringent 'doubling' criterion when they are not. In addition, a new graphical interpretation is introduced that permits a straightforward visual comparison of pairs of indices across a wide range within a parameter space based on species and organism numbers.

Novel GPR120 agonist TUG891 modulates fat taste perception and preference and activates tongue-brain-gut axis in mice.

GPR120 is implicated as a lipid receptor in the oro-sensory detection of dietary fatty acids. However, the effects of GPR120 activation on dietary fat intake or obesity are not clearly understood. We investigated to determine whether the binding of TUG891, a novel GPR120 agonist, to lingual GPR120 modulates fat preference in mice. We explored the effects of TUG891 on obesity-related hormones and conducted behavioral choice tests on mice to better understand the physiologic relevance of the action of TUG891. In cultured mouse and human taste bud cells (TBCs), TUG891 induced a rapid increase in Ca2+ by acting on GPR120. A long-chain dietary fatty acid, linoleic acid (LA), also recruited Ca2+ via GPR120 in human and mouse TBCs. Both TUG891 and LA induced ERK1/2 phosphorylation and enhanced in vitro release of glucagon-like peptide-1 from cultured human and mouse TBCs. In situ application of TUG891 onto the tongue of anesthetized mice triggered the secretion of pancreatobiliary juice, probably via the tongue-brain-gut axis. Furthermore, lingual application of TUG891 altered circulating concentrations of cholecystokinin and adipokines, associated with decreased circulating LDL, in conscious mice. In behavioral tests, mice exhibited a spontaneous preference for solutions containing either TUG891 or LA instead of a control. However, addition of TUG891 to a solution containing LA significantly curtailed fatty acid preference. Our study demonstrates that TUG891 binds to lingual GPR120 receptors, activates the tongue-brain-gut axis, and modulates fat preference. These findings may support the development of new fat taste analogs that can change the approach to obesity prevention and treatment.

The rs1527483, but not rs3212018, CD36 polymorphism associates with linoleic acid detection and obesity in Czech young adults.

Recent evidence has raised the possibility of the existence of a sixth taste modality - that is, taste for fat - which is mediated by lingual CD36 and plays a role in obesity. Consequently, the genetic polymorphism of CD36 has been shown to be associated with altered oro-sensory detection of dietary lipids. In the present study, we investigated the relationship between oro-sensory perception of linoleic acid (LA), two CD36 polymorphisms (rs1527483 and rs3212018), obesity parameters and craving habits for dietary lipids in young Czech adults. We also sequenced 5 and 6 exons of CD36 to trace out any new mutation that might be responsible for the difference in taste perception. We observed that craving for dietary lipids was correlated with anthropometric parameters (P<0·05) and LA detection threshold (P=0·033). The participants with the CC genotype of the rs1527483 polymorphism had lower BMI (P=0·011), waist circumference (P=0·005), waist:height ratio (P=0·010) and higher sensitivity for LA (P=0·037) than the participants with the CT and TT genotypes. Interestingly, we did not observe any association between the rs3212018 polymorphism and the studied parameters. Moreover, we did not observe any mutation in exons 5 and 6 of the CD36 gene in these subjects. Finally, we can state that rs1527483, but not rs3212018, is associated with high body weight in young Czech subjects.

Interventions for chronic kidney disease-associated restless legs syndrome.

BACKGROUND: Restless legs syndrome (RLS) is defined as the spontaneous movement of the limbs (mainly legs) associated with unpleasant, sometimes painful sensation which is relieved by moving the affected limb. Prevalence of RLS among people on dialysis has been estimated between 6.6% and 80%. RLS symptoms contribute to impaired quality of life and people with RLS are shown to have increased cardiovascular morbidity and mortality.Various pharmacological and non-pharmacological interventions have been used to treat primary RLS. However, the evidence for use of these interventions in people with chronic kidney disease (CKD) is not well established. The agents used in the treatment of primary RLS may be limited by the side effects in people with CKD due to increased comorbidity and altered drug pharmacokinetics. OBJECTIVES: The aim of this review was to critically look at the benefits, efficacy and safety of various treatment options used in the treatment of RLS in people with CKD and those undergoing renal replacement therapy (RRT). We aimed to define different group characteristics based on CKD stage to assess the applicability of a particular intervention to an individual patient. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Specialised Register to 12 January 2016 through contact with the Information Specialist using search terms relevant to this review. SELECTION CRITERIA: Randomised controlled trials (RCT) and quasi-RCTs that assessed the efficacy of an intervention for RLS in adults with CKD were eligible for inclusion. Studies investigating idiopathic RLS or RLS secondary to other causes were excluded. DATA COLLECTION AND ANALYSIS: Two authors independently assessed studies for eligibility and conducted risk of bias evaluation. Results were expressed as risk ratios (RR) and their 95% confidence intervals (CI) for dichotomous outcomes, and mean difference (MD) and 95% CI for continuous outcomes. MAIN RESULTS: We included nine studies enrolling 220 dialysis participants. Seven studies were deemed to have moderate to high risk of bias. All studies were small in size and had a short follow-up period (two to six months). Studies evaluated the effects of six different interventions against placebo or standard treatment. The interventions studied included aerobic resistance exercise, gabapentin, ropinirole, levodopa, iron dextran, and vitamins C and E (individually and in combination).Aerobic resistance exercise showed a significant reduction in severity of RLS compared to no exercise (2 studies, 48 participants: MD -7.56, 95% CI -14.20 to -0.93; I2 = 65%), and when compared to exercise with no resistance (1 study, 24 participants: MD -11.10, 95% CI -17.11 to -5.09), however there was no significant reduction when compared to ropinirole (1 study, 22 participants): MD -0.55, 95% CI -6.41 to 5.31). There were no significant differences between aerobic resistance exercise and either no exercise or ropinirole in the physical or mental component summary scores (using the SF-36 form). Improvement in sleep quality varied. There was no significant difference in subjective sleep quality between exercise and no exercise; however one study reported a significant improvement with ropinirole compared to resistance exercise (MD 3.71, 95% CI 0.89 to 6.53). Using the Epworth Sleepiness Scale there were no significant differences between resistance exercise and no exercise, ropinirole, or exercise with no resistance. Two studies reported there were no adverse events and one study did not mention if there were any adverse events. In one study, one patient in each group dropped out but the reason for dropout was not reported. Two studies reported no adverse events and one study did not report adverse events.Gabapentin was associated with reduced RLS severity when compared to placebo or levodopa, and there was a significant improvement in sleep quality, latency and disturbance reported in one study when compared to levodopa. Three patients dropped out due to lethargy (2 patients), and drowsiness, syncope and fatigue (1 patient).Because of a short duration of action, rebound and augmentation were noted with levodopa treatment even though it conferred some benefit in reducing the symptoms of RLS. Reported adverse events were severe vomiting, agitation after caffeine intake, headaches, dry mouth, and gastrointestinal symptoms.One study (25 participants) reported iron dextran reduced the severity of RLS at weeks one and two, but not at week four. Vitamins C, E and C plus E (1 study, 60 participants) helped the symptoms of RLS with minimal side effects (nausea and dyspepsia) but more evidence is needed before any conclusions can be drawn. AUTHORS' CONCLUSIONS: Given the small size of the studies and short follow-up, it can only be concluded that pharmacological interventions and intra-dialytic exercise programs have uncertain effects on RLS in haemodialysis patients. There have been no studies performed in non-dialysis CKD, peritoneal dialysis patients, or kidney transplant recipients. Further studies are warranted before any conclusions can be drawn. Aerobic resistance exercise and ropinirole may be suitable interventions for further evaluation.

Placental infiltration of inflammatory markers in gestational diabetic women.

Gestational diabetes mellitus (GDM) is pathology of glucose intolerance during pregnancy. It is influenced by maternal hyperglycemia and insulinemia through placental circulation. The study was undertaken to investigate the implication of pro-inflammatory factors in the placenta of GDM women. Thirty GDM women have delivered macrosomic babies, and 30 healthy age-matched pregnant women have delivered non macrosomic babies, were recruited in the study. The mRNAs encoding for IL-6, TLR4, TGF-ß, CD68, CD14, EMR-1, CCL2, TCR-α, T-bet, GATA-3, leptin and adiponectin were quantified in placental samples by using RT-qPCR. The mRNA expression of the pro-inflammatory factors, i.e., IL-6, TLR4 and TGF-ß, was increased in GDM placenta. The mRNA expression of markers of infiltration of macrophage, i.e., CD68, CD14 and EMR-1, was higher in the GDM placenta than the control placenta. The expression of mRNA of TCR-α, an indicator of T-cell infiltration, was significantly higher in the GDM placenta. Interestingly, the expression of mRNA of GATA-3, an indicator of Th2 phenotype differentiation, was unregulated in the GDM placenta. Leptin and adiponectin mRNAs were also significantly increased in the placenta of the GDM group. Our results revealed that there is an increase of inflammation in the GDM placenta which might be involved, in part, in the pathogenesis of macrosomia.

Detection of antibody-drug conjugate-induced interstitial lung disease using circulating cell-free DNA.

BACKGROUND: The increasing use and anticipated future adoption of antibody-drug conjugates (ADCs) present a significant challenge in identifying and monitoring patients for the development of potentially fatal drug-induced interstitial lung disease (ILD). We sought to apply a tissue-specific methylation analysis of circulating cell-free DNA (cfDNA) to measure lung damage in patients with trastuzumab deruxtecan (T-DXd)-related ILD. PATIENTS AND METHODS: We describe a patient with metastatic human epidermal growth factor receptor 2 (HER2)-positive endometrial cancer who developed ILD during T-DXd treatment. Blood samples collected at the time of ILD diagnosis, after recovery, and following rechallenge were studied for lung damage using lung-specific methylation markers in cfDNA. To validate the findings, we also tested plasma samples from an additional cohort of patients with HER2-positive metastatic breast cancer treated with T-DXd. RESULTS: In patients with HER2-positive metastatic cancer treated with T-DXd, the presence of an active ILD, as assessed clinically and using chest computed tomography, was associated with increased levels of lung-derived cfDNA. CONCLUSIONS: This proof-of-concept study demonstrates that liquid biopsy can be developed as a valuable tool for detecting and monitoring ADC-related ILD. Its low cost and simplicity make it a potential alternative to current imaging methods, warranting further clinical development.

Distinct binding hotspots for natural and synthetic agonists of FFA4 from in silico approaches.

FFA4 has gained interest in recent years since its deorphanization in 2005 and the characterization of the Free Fatty Acids receptors family for their therapeutic potential in metabolic disorders. The expression of FFA4 (also known as GPR120) in numerous organs throughout the human body makes this receptor a highly potent target, particularly in fat sensing and diet preference. This offers an attractive approach to tackle obesity and related metabolic diseases. Recent cryo-EM structures of the receptor have provided valuable information for a potential active state although the previous studies of FFA4 presented diverging information. We performed molecular docking and molecular dynamics simulations of four agonist ligands, TUG-891, Linoleic acid, α-Linolenic acid, and Oleic acid, based on a homology model. Our simulations, which accumulated a total of 2 µs of simulation, highlighted two binding hotspots at Arg992.64 and Lys293 (ECL3). The results indicate that the residues are located in separate areas of the binding pocket and interact with various types of ligands, implying different potential active states of FFA4 and a highly adaptable binding intra-receptor pocket. This article proposes additional structural characteristics and mechanisms for agonist binding that complement the experimental structures.

Therapeutic potential of ramipril, losartan, and spironolactone against sepsis-associated liver tissue injury induced by cecal ligation and puncture in rats.

OBJECTIVE: Sepsis-associated liver injury is responsible for the high morbidity and mortality rates seen with septic shock. Activation of the renin-angiotensin-aldosterone system (RAAS) is an essential counteractive mechanism during the hypotensive phase of sepsis; however, excessive activation is associated with exaggerated pro-oxidant and inflammatory response, which aggravates organ damage. This study aimed to evaluate the effect of RAAS inhibition on sepsis-induced liver damage. MATERIALS AND METHODS: The cecal ligation and puncture (CLP) model was employed as a model of sepsis. Rats were divided into five groups: sham-operated, vehicle-treated septic rats, septic rats treated with ramipril in a dose of 10 mg/kg, septic rats treated with losartan in a dose of 20 mg/kg, and finally septic rats treated with spironolactone in a dose of 25 mg/kg. Rats received the treatment one hour after induction. Twenty-four hours later, rats were euthanized, and serum samples and liver tissue were collected to evaluate liver function and hepatic oxidative, anti-oxidative, inflammatory, and apoptotic markers. The microscopic integrity of the hepatic tissue was also assessed. RESULTS: The results of our study showed that all the treatments used ameliorated sepsis-induced liver injury. This was reflected by improved liver function parameters and histopathological appearance of liver tissue. Treatment with ramipril, losartan, or spironolactone reduced tissue malondialdehyde (MDA), nitric oxide, activated caspase-3, and TNF-α. Moreover, these drugs increased hepatic reduced-glutathione (GSH) levels, superoxide dismutase (SOD) activity, and proliferating cell nuclear antigen (PCNA) expression. CONCLUSIONS: Administration of ramipril, losartan, or spironolactone after CLP produced a hepatoprotective effect in rats, possibly by reducing oxidative stress, inflammation, and apoptosis.

Inflammation and impaired endothelium-dependant vasodilatation in non obese women with gestational diabetes mellitus: preliminary results.

BACKGROUND: To evaluate whether abnormal endothelial function, a common finding in gestational diabetes mellitus (GDM) pregnancies, can be explained by inflammatory cytokines. METHODS: Forearm skin blood flow (FSBF), into response to acetylcholine (Ach) (endothelium-dependent vasodilatation), were measured in 24 pregnant control subjects and 28 gestational diabetes mellitus (GDM) women, in the third trimester of gestation. A fasting glycemic and lipidic panel was obtained, and inflammatory cytokines (TNF-α and IL-6) and adiponectin were also determined. RESULTS: FSBF is significantly reduced in GDM group compared with control subjects (344.59 ± 57.791 vs.176.38 ± 108.52, P < 0.05). Among all subjects, FSBF showed a strong negative correlation with TNF-α and IL-6 (r = -0.426, P < 0.0001 and r = -0.564, P < 0.0001, respectively) and positive correlation with adiponectin (r = 0.468, P < 0.0001). CONCLUSIONS: Endothelial function, an early marker of macrovascular disease, is present in non-obese pregnancies complicated by GDM. This alteration seems to be directly related to inflammatory status, which may represent a patho-physiological link between GDM and type 2 diabetes and, later on, metabolic syndrome.

Anti-hyperglycemic effects of three medicinal plants in diabetic pregnancy: modulation of T cell proliferation.

BACKGROUND: Populations in Africa mostly rely on herbal concoctions for their primarily health care, but so far scientific studies supporting the use of plants in traditional medicine remain poor. The present study was undertaken to evaluate the anti-hyperglycemic effects of Picralima nitida (seeds), Nauclea latifolia (root and stem) and Oxytenanthera abyssinica (leaves) commonly used, in diabetic pregnancy. METHODS: Pregnant wistar rats, rendered diabetic by multiple low injections of streptozotocin, were treated with selected plant extracts based on their antioxidant activities. Vitamin C concentrations, fatty acid compositions and phytochemical analysis of plants extracts were determined. Effect of selected plant extracts on human T cell proliferation was also analysed. RESULTS: All analysed plant extracts exhibited substantial antioxidant activities probably related to their content in polyphenols. Picralima nitida exhibited the highest antioxidant capacity. Ethanolic and butanolic extracts of Picralima nitida, butanolic extract of Nauclea latifolia and ethanolic extract of Oxytenanthera abyssinica significantly decreased hyperglycemia in the diabetic pregnant rats. Butanolic extract of Picralima, also appeared to be the most potent immunosuppressor although all of the analysed extracts exerted an immunosuppressive effect on T cell proliferation probably due to their linolenic acid (C18:3n-3) and/or alkaloids content. Nevertheless, all analysed plants seemed to be good source of saturated and monounsaturated fatty acids. CONCLUSION: By having antioxidant, anti-hyperglycemic and immunosuppressive activities, these plants could be good candidates in the treatment of diabetes and diabetic pregnancy.

New Insights Into the Anticancer Effects of p-Coumaric Acid: Focus on Colorectal Cancer.

Colorectal cancer is considered the second most deadly cancer in the world. Studies have indicated that diet can prevent the risk of developing colorectal cancer. Recently, there has been an increasing interest in polyphenols due to their plausible effect on cancer prevention and treatment. p-Coumaric acid (p-CouA), a phenolic compound, is a cinnamic acid derivative found in several fruits, vegetables, and herbs. A growing body of evidence suggests that p-CouA may be an effective agent for preventing and managing colorectal cancer. In this current review, we briefly highlight the bioavailability of p-CouA. We also provide an up-to-date overview of molecular mechanisms underlying its anticancer effects, focusing on anti-inflammatory and antioxidant potentials, apoptosis induction, and cell cycle blockade. Finally, we discuss the impact of p-CouA on clonogenicity and multidrug resistance of colorectal cancer cells.

A METHOD TO IDENTIFY AND LOCALIZE A SINGLE HOT PARTICLE IN THE LUNGS USING AN ARRAY OF HIGH-PURITY GERMANIUM DETECTORS FOR IMPROVED ESTIMATE OF THE DEPOSITED ACTIVITY.

A new method has been developed to identify and localize a single hot particle in the lungs using an array of four high-purity germanium detectors. The method is based upon calculating a set of three count rate ratios (generated by each individual detector in the array) that are evaluated in sequence to designate whether the measured deposition can be associated with a hot particle rather than the default assumption of a uniform activity distribution. Identification and localization of the hot particle are determined from a single in vivo measurement in which detectors are positioned above and below the thorax. The method was tested using an anthropomorphic thorax phantom in which point sources of 241Am, 137Cs and 60Co were individually inserted in the lungs at 15 different locations and were measured using a scanning bed whole-body counter. Depending upon source location and photon energy, a bias of -35% up to +76% could be introduced by falsely assuming a uniform activity distribution in the lungs. This bias would directly translate to an erroneous dose estimate to the lungs. It was demonstrated that by using the appropriate detector efficiencies for the single hot particle, the bias associated with the activity determination is reduced to <10% and ~2% in average.

Anti-inflammatory effects of the chloroform extract of Pulicaria guestii ameliorated the neutrophil infiltration and nitric oxide generation in rats.

Pulicaria guestii Rech.f. & Rawi is a fragrant, perennial herb, which grows wild, west of Al-Madinah, Saudi Arabia. Several reports were published on the anti-inflammatory activity of the sesquiterpene lactones, phenolics and flavonoids, which constitute the main active constituents of the members of the genus Pulicaria. The present study was designed to explore the potential anti-inflammatory effect of P. guestii in several experimental models. The methanol extract of the dried aerial parts of P. guestii was extracted with petroleum ether, chloroform and n-butanol. The chloroform extract was analysed on TLC and examined under UV and visible light in presence of AlCl(3) spray. The free radical scavenging activity and the total phenolic content in the CHCl(3) extract were estimated. The crude methanol extract and the CHCl(3) fraction were examined against carrageenin-induced paw edema and ear edema induced by croton oil application. The crude methanolic extract significantly reduced carrageenin-induced rat paw edema. After fractionation, the chloroform fraction caused significant reduction in carrageenin-induced rat paw edema in addition to diminishing prostaglandin E(2) (PGE(2)) in the inflammatory exudates. Topical application of chloroform fraction significantly reduced rat ear edema induced by croton oil application. In the same model, chloroform fraction reduced neutrophil infiltration, as indicated by the significant decrease in myeloperoxidase activity, and ameliorated histopathological changes induced by croton oil application. In lipopolysaccharide-induced inflammation in rat air pouch, chloroform fraction significantly reduced the nitric oxide level and tumor necrosis factor-α release. In conclusion, the chloroform fraction of P. guestii extract possesses anti-inflammatory activity in several experimental models. Further investigations are needed to identify the active constituents responsible for this anti-inflammatory activity.

Implication of TRPC3 channel in gustatory perception of dietary lipids.

AIM: The pathogenesis of obesity has been associated with high intake of dietary fat, and some recent studies have explored the cellular mechanisms of oro-sensory detection of dietary fatty acids. We further assessed the role of transient receptor potential canonical (TRPC) channels in oro-sensory perception of dietary lipids. METHODS: We determined by RT-qPCR and western blotting the expression of TRPC3/6/7 channels in mouse fungiform taste bud cells (mTBC). Immunocytochemistry was used to explore whether TRPC3 channels were co-expressed with fatty acid receptors. We employed wild-type (WT) mTBC, and those transfected with small interfering RNAs (siRNAs) against TRPC3 or STIM1. Ca2+ signalling was studied in TBC from TRPC3-/- mice and their WT littermates. RESULTS: We demonstrate that mouse fungiform taste bud cells (mTBC) express TRPC3, but not TRPC6 or TRPC7 channels, and their inactivation by siRNA or experiments on TBC from TRPC3-/- mice brought about a decrease in fatty acid-induced gustatory Ca2+ signalling, coupled with taste bud CD36 lipid sensor. TRPC3 channel activation was found to be under the control of STIM1 in lingual mTBC. Behavioural studies showed that spontaneous preference for a dietary long-chain fatty acid was abolished in TRPC3-/- mice, and in mice wherein lingual TRPC3 expression was silenced by employing siRNA. CONCLUSION: We report that lingual TRPC3 channels are critically involved in fat taste perception.

Growth factor concentrations and their placental mRNA expression are modulated in gestational diabetes mellitus: possible interactions with macrosomia.

BACKGROUND: Gestational diabetes mellitus (GDM) is a form of diabetes that occurs during pregnancy. GDM is a well known risk factor for foetal overgrowth, termed macrosomia which is influenced by maternal hypergycemia and endocrine status through placental circulation. The study was undertaken to investigate the implication of growth factors and their receptors in GDM and macrosomia, and to discuss the role of the materno-foeto-placental axis in the in-utero regulation of foetal growth. METHODS: 30 women with GDM and their 30 macrosomic babies (4.75 +/- 0.15 kg), and 30 healthy age-matched pregnant women and their 30 newborns (3.50 +/- 0.10 kg) were recruited in the present study. Serum concentrations of GH and growth factors, i.e., IGF-I, IGF-BP3, FGF-2, EGF and PDGF-B were determined by ELISA. The expression of mRNA encoding for GH, IGF-I, IGF-BP3, FGF-2, PDGF-B and EGF, and their receptors, i.e., GHR, IGF-IR, FGF-2R, EGFR and PDGFR-beta were quantified by using RT-qPCR. RESULTS: The serum concentrations of IGF-I, IGF-BP3, EGF, FGF-2 and PDGF-B were higher in GDM women and their macrosomic babies as compared to their respective controls. The placental mRNA expression of the growth factors was either upregulated (FGF-2 or PDGF-B) or remained unaltered (IGF-I and EGF) in the placenta of GDM women. The mRNA expression of three growth factor receptors, i.e., IGF-IR, EGFR and PDGFR-beta, was upregulated in the placenta of GDM women. Interestingly, serum concentrations of GH were downregulated in the GDM women and their macrosomic offspring. Besides, the expression of mRNAs encoding for GHR was higher, but that encoding for GH was lower, in the placenta of GDM women than control women. CONCLUSIONS: Our results demonstrate that growth factors might be implicated in GDM and, in part, in the pathology of macrosomia via materno-foeto-placental axis.

Effects of pentoxifylline on coagulation profile and disseminated intravascular coagulation incidence in Egyptian septic neonates.

BACKGROUND AND OBJECTIVES: Neonatal sepsis is frequently associated with pathological activation of the coagulation system, leading to microcirculatory derangement and multiple organ dysfunction syndrome (MODS). The key role in the pathogenesis of sepsis has been attributed to proinflammatory cytokines. These trigger the development of disseminated intravascular coagulation (DIC) via the tissue factor-dependent pathway of coagulation. Pentoxifylline (PTX), a methylxanthine derivative that is used in peripheral vascular disease, has the potential to modify inflammatory response. The current work was designed to evaluate the potential protective effects of PTX against sepsis-induced microcirculatory derangement in Egyptian neonates. METHODS: A double-blind placebo-controlled quasi-randomized design was used. Thirty-seven neonates with sepsis were randomly allocated into two groups. Seventeen patients were given PTX (5 mg/kg/h for 6 h; for 6 successive days). Twenty patients received equivalent volume of normal saline and represented the placebo group. Prothrombin time (PT), Activated partial thromboplastin time (APTT), fibrinogen, d-dimer, C-reactive protein (CRP), complete blood count (CBC), also hemodynamic parameters comprising arterial blood pressure, heart rate, capillary refill and urinary output were assessed in both groups before and after treatment. RESULTS: Coagulation parameters in the two groups showed no significant differences. However, a higher incidence of DIC was observed in the placebo group neonates. PTX significantly lowered the percentage of bleeding (P = 0.0128) and less frequent use of FFP was observed in the PTX group (35.53% in PTX group vs. 80% in placebo group, P = 0.003). Incidence of MODS was significantly lower (P = 0.037) and hospital stay duration of survivors was significantly shorter (P = 0.044) in the PTX treated-infants. CONCLUSION: Pentoxifylline protects against sepsis-induced microcirculatory derangement in neonates. It significantly lowered the incidence of bleeding and MODS and shortened the length of hospital stay.

Zizyphus lotus L. (Desf.) modulates antioxidant activity and human T-cell proliferation.

BACKGROUND: Zizyphus lotus L. (Desf.) also known as Jujube, is a deciduous shrub which belongs to Rhamnaceae family. This plant is used in Algerian traditional medicine for its anti-diabetic, sedative, analgesic, anti-inflammatory and hypoglycaemic activities. In the present study, we determined the concentrations of different vitamins (vitamin A, C and E) and fatty acids in root, stem, leaves, fruit pulp and seed of Zizyphus lotus L. (Desf.) and assessed the effects of their aqueous extracts on antioxidant status and human T-cell proliferation. METHODS: Aqueous filtrates from different parts, i.e, root, leaf, stem, fruit pulp and seed, of Zizyphus lotus L. (Desf.) were prepared. Vitamin C levels were determined by precipitating with 10% trichloroacetic acid and vitamin A and E were assessed by HPLC. Lipid composition of these extracts was determined by gas-liquid chromatography. Anti-oxidant capacity was evaluated by using anti-radical resistance kit [Kit Radicaux Libres (KRL@; Kirial International SA, Couternon, France)]. T-cell blastogenesis was assessed by the incorporation of 3H-thymidine. IL-2 gene expression was evaluated by RT-qPCR. RESULTS: Our results show that fruit pulp contained higher vitamin A and C contents than other parts of the plant. Furthermore, the fruit pulp was the richest source of linoleic acid (18:2n-6), a precursor of n-6 fatty acids. Fruit seeds possessed higher vitamin C levels than leaves, roots and stem. The leaves were the richest source of vitamin E and linolenic acid (18:3n-3), a precursor of n-3 fatty acids. The antioxidant capacity of the different extracts, measured by KRL@ test, was as follows: pulp < seed < leaf < root < stem. As far as T-cell proliferation is concerned, we observed that the different extracts of Zizyphus lotus L. (Desf.) exerted immunosuppressive effects. CONCLUSION: Seed extracts exerted the most potent immunosuppressive effects on T cell proliferation and IL-2 mRNA expression. The results of the present study are discussed in the light of their use to modulate the immune-mediated diseases.

Preference for dietary fat: From detection to disease.

Recent advances in the field of taste physiology have clarified the role of different basic taste modalities and their implications in health and disease and proposed emphatically that there might be a distinct cue for oro-sensory detection of dietary long-chain fatty acids (LCFAs). Hence, fat taste can be categorized as a taste modality. During mastication, LCFAs activate tongue lipid sensors like CD36 and GPR120 triggering identical signaling pathways as the basic taste qualities do; however, the physico-chemical perception of fat is not as distinct as sweet or bitter or other taste sensations. The question arises whether "fat taste" is a basic or "alimentary" taste. There is compelling evidence that fat-rich dietary intervention modulates fat taste perception where an increase or a decrease in lipid contents in the diet results, respectively, in downregulation or upregulation of fat taste sensitivity. Evidently, a decrease in oro-sensory detection of LCFAs leads to high fat intake and, consequently, to obesity. In this article, we discuss recent relevant advances made in the field of fat taste physiology with regard to dietary fat preference and lipid sensors that can be the target of anti-obesity strategies.

Galaxies, human eyes, and artificial neural networks.

The quantitative morphological classification of galaxies is important for understanding the origin of type frequency and correlations with environment. However, galaxy morphological classification is still mainly done visually by dedicated individuals, in the spirit of Hubble's original scheme and its modifications. The rapid increase in data on galaxy images at low and high redshift calls for a re-examination of the classification schemes and for automatic methods. Here are shown results from a systematic comparison of the dispersion among human experts classifying a uniformly selected sample of more than 800 digitized galaxy images. These galaxy images were then classified by six of the authors independently. The human classifications are compared with each other and with an automatic classification by an artificial neural network, which replicates the classification by a human expert to the same degree of agreement as that between two human experts.