Editorial: Probiotics, Gut Microbiota and Immunomodulation: Is this the Key to Counteract the Allergy Epidemics?

Allergic diseases have been described since the antiquities [1], but major advancements on understanding of their pathogenic mechanisms and clinical implications date to the end of the 19th and the first half of the 20th century [2, 3]. In the meantime, during the last decades, the prevalence of allergic diseases remarkably increased, paving the way to the definition of “allergy epidemics” [4]. But what happened in the second half of the 19th century that gave rise to this phenomenon? As far as we know, at least two major changes took place, which led to an increase of allergic diseases. The first one was a major change in life and social conditions, with decrease of family size, people progressively moving from the countryside to the cities, and consistent improvements in public hygiene, with widespread availability of clean water and use of antibiotics, just to name two [4]. The second one was the increasing concentration of airborne pollens, due to the diffusion of new grasses, such as Lolium perenne in England in the late 19th century, and to the increasing presence of infesting grasses due to changes in farming techniques and increase in arable farming. By the mid-forties, hay fever became such a severe health problem in the New York city area that a ragweed eradication campaign was initiated by the city council [5]. If the link between the increase of airborne pollens in the air and allergic diseases caused by the pollens themselves is clear, this is not the same for the first explanation. In 1989, David P. Strachan published on The Lancet the results of his epidemiologic investigation on 17414 British children who were followed-up until the age of 23 [6]. He aimed to investigate the relationship between the increase of hay fever and sixteen different perinatal, social and environmental factors. What he found was a striking association of hay fever with family size and position in the household during childhood [6]. In his evaluation, the single most influential variable was the number of older children in the household, and he hypothesized that allergies could be prevented – during childhood – by cross-infections among family members, facilitated by unhygienic contact with other siblings. This was the birth of the “hygiene hypothesis”, which is still today a milestone to explain the rise of allergic diseases [6, 7]. In the last decades of the 20th century, new information came from in vitro studies about CD4+ T-lymphocyte subpopulations [8]. T Helper-1 (Th1) cells were characterized as T lymphocytes capable of prevalent production, in response to microbial stimuli, of interleukin-2 (IL-2), interferon γ (IFN-γ), and transforming growth factor β (TGF-β), subsequently referred to as “Th1-cytokines”; these cytokines were recognized a prominent role in defense against most infectious agents [8]. Th2 cells, on the contrary, were characterized by the prevalent production of IL-4, IL-5, IL-9, and IL-13 (Th2-cytokines) who gave rise to an eosinophilic-rich immune response, primarily implicated in immunity against parasites and multicellular organisms but less crucial for immune responses in modern westernized countries [8]

House dust mite-related respiratory allergies and probiotics: a narrative review

Abstract The socio-economic burden of allergic respiratory conditions on continental Europe is even higher than that of mainstream diseases, such as diabetes and cardiovascular disease, as allergic rhinitis alone accounts for billions of Euros in healthcare expenses across Europe. House dust mites (HDM) are one of the most common triggers behind allergic rhinitis and asthma. The role of probiotics in the treatment and prevention of some allergic conditions, such as atopic dermatitis, is already well recognized, whereas evidence about their efficacy in patients with respiratory allergies—while increasing—is still limited. Here the current evidence for the use of probiotics in patients with allergic rhinitis and/or asthma is discussed

Lactose Maldigestion, Malabsorption, and Intolerance: A Comprehensive Review with a Focus on Current Management and Future Perspectives

Milk is a fundamental component of the diet of every mammal; nevertheless, not every individual can tolerate this kind of food, especially in adulthood. However, lactose intolerance has only been recognized in the last 50 years, and currently, lactose intolerance is defined as a clinical syndrome characterized by pain, abdominal distention, flatulence, and diarrhoea that occur after lactose consumption. Lactose is currently a common disaccharide in human nutrition, both in breastfed infants and in adults, but its digestion requires a specialized enzyme called lactase. The genetically programmed reduction in lactase activity during adulthood affects most of the world’s adult population and can cause troublesome digestive symptoms, which may also vary depending on the amount of residual lactase activity; the small bowel transit time; and, especially, the amount of ingested lactose. Several diagnostic tests are currently available for lactose intolerance, but the diagnosis remains challenging. The treatment for lactose intolerance mainly consists of reducing or eliminating the dietetic amount of lactose until the symptoms disappear, but this is hard to achieve, as lactose is present in dairy products and is even commonly used as a food additive. In addition to dietetic restriction of lactose-containing foods, lactase can be administered as an enzymatic food supplement, but its efficacy is still controversial. Recently, probiotics have been proposed for the management of lactose intolerance; certain probiotic strains have shown specific β-galactosidase activity, thus aiding in the digestion of lactose. The aim of this paper was to review the current knowledge about lactose intolerance and to discuss the potential for the use of specific probiotic strains such as dietary supplements in lactose-intolerant patients

Prevention of post-contrast kidney injury in patients with cancer

Post-contrast acute kidney injury is defined as a nephropathy with an increase in serum creatinine of >0.3 mg/dL (or >26.5 μmol/L) or >1.5-times the baseline within 48–72 h of intravascular administration of a contrast medium. Patients with cancer have an increased risk of post-contrast acute kidney injury not only related to the frequent use of contrast medium for computed tomography scans but also to other factors, including the type of tumour, age, oncological therapies, use of other nephrotoxic agents and dehydration. Preventive strategies were developed and may be applied to different risk profiles. Patients at risk may be detected by recently published risk scores

Tolerance to cannabinoid response on the myenteric plexus of guinea-pig ileum and human small intestinal strips

1. We studied tolerance to cannabinoid agonist action by comparing the in vitro inhibition of electrically evoked contractions of longitudinal muscle from small intestine of human and guinea-pig (myenteric plexus preparations) after 48-h incubation with the synthetic agonist (+) WIN 55,212-2. We also investigated the intrinsic response to the selective cannabinoid CB(1) receptor antagonist rimonabant in control and tolerant strips. 2. (+) WIN 55,212-2 inhibited guinea-pig (IC(50) 4.8 nM) and human small intestine (56 nM) contractions with similar potency before or after 48-h incubation in drug-free conditions; this effect was competitively antagonized by rimonabant (pA(2), 8.4, 8.2). A 48-h preincubation with (+) WIN 55,212-2, but not with (−) WIN 55,212-3, completely abolished the acute agonist response in both tissue preparations. The opiate K-receptor agonist U69593 inhibited human small intestine contractions with a similar potency in control and strips tolerant to (+) WIN 55,212-2, IC(50) 39 and 43 nM. 3. Unlike human tissue, in guinea-pig small intestine, which has a high level of endocannabinoids, rimonabant alone increased the twitches induced by the electrical field stimulation (EC(50) 100 nM) with a maximal effect of 123%. 4. In strips tolerant to (+) WIN 55,212-2, rimonabant markedly increased (155%) the electrical twitches in human ileum and in guinea-pig myenteric plexus smooth muscle (133%). 5. This study shows tolerance can be induced to the cannabinoids' action in intestinal strips of human and guinea-pig by long in vitro incubation with the agonist (+) WIN 55,212-2

In vitro and in vivo pharmacological characterization of ethyl-4-[trans-4-[((2S)-2-hydroxy-3-[4-hydroxy-3[(methylsulfonyl)amino]-phenoxy]propyl) amino]cyclohexyl]benzoate hydrochloride (SAR150640), a new potent and selective human beta3-adrenoceptor agonist for the treatment of preterm labor.

International audienceEthyl-4-[trans-4-[((2S)-2-hydroxy-3-[4-hydroxy-3[(methylsulfonyl)amino] phenoxy]propyl) amino]cyclohexyl]benzoate hydrochloride (SAR150640) was characterized as a new potent and selective beta(3)-adrenoceptor agonist for the treatment of preterm labor. SAR150640 and its major metabolite, the corresponding acid 4-[trans-4-[((2S)-2-hydroxy-3-[4-hydroxy-3[(methylsulfonyl) amino] phenoxy]propyl)amino]cyclohexyl]benzoic acid (SSR500400), showed high affinity for beta(3)-adrenoceptors (K(i) = 73 and 358 nM) and greater potency than (-)-isoproterenol in increasing cAMP production in membrane preparations from human neuroblastoma cells (SKNMC), which express native beta(3)-adrenoceptors (pEC(50) = 6.5, 6.2, and 5.1, respectively). SAR150640 and SSR500400 also increased cAMP production in membrane preparations from human uterine smooth muscle cells (UtSMC), which also express native beta(3)-adrenoceptors (pEC(50) = 7.7 and 7.7, respectively). In these cells, SAR150640 dose-dependently inhibited oxytocin-induced intracellular Ca(2+) mobilization and extracellular signal-regulated kinase 1/2 phosphorylation. SAR150640 and SSR500400 had no beta(1)- or beta(2)-agonist or antagonist activity in guinea pig atrium and trachea, or in human isolated atrium and bronchus preparations. Both compounds concentration-dependently inhibited spontaneous contractions in human near-term myometrial strips, with greater potency than salbutamol and 4-[3-[(1,1-dimethylethyl)-amino]-2-hydroxypropoxy]-1,3-dihydro-2H-benzimidazol-2-one hydrochloride (CGP12177) (pIC(50) = 6.4, 6.8, 5.9, and 5.8, respectively), but with similar potency to (-)-isoproterenol and atosiban (oxytocin/vasopressin V(1)a receptor antagonist). SAR150640 also inhibited the contractions induced by oxytocin and prostaglandin F(2alpha). In vivo, after intravenous administration, SAR150640 (1 and 6 mg/kg), but not atosiban (6 mg/kg), dose-dependently inhibited myometrial contractions in conscious unrestrained female cynomolgus monkeys, with no significant effects on heart rate or blood pressure. In contrast, salbutamol (50 and 250 microg/kg) had no inhibitory effect on uterine contractions, but it dose-dependently increased heart rate. These findings indicate a potential for the therapeutic use of SAR150640 in mammals during preterm labor