Adjuvant treatment with a symbiotic in patients with inflammatory non-allergic rhinitis.

Inflammatory non-allergic rhinitis (INAR) is characterized by the presence of an inflammatory infiltrate and a non-IgE-mediated pathogenesis. This retrospective, controlled, multicentre study investigated whether a symbiotic, containing Lactobacillus acidophilus NCFM, Bifidobacterium lactis, and fructo-oligosaccharides (Pollagen®, Allergy Therapeutics, Italy), prescribed as adjunctive therapy to a standard pharmacological treatment, was able to reduce symptom severity, endoscopic features, and nasal cytology in 93 patients (49 males and 44 females, mean age 36.3±7.1 years) with INAR. The patients were treated with nasal corticosteroid, oral antihistamine, and isotonic saline. At randomization, 52 patients were treated also with symbiotic as adjunctive therapy, whereas the remaining 41 patients served as controls. Treatment lasted for 4 weeks. Patients were visited at baseline, after treatment, and after 4-week follow-up. Adjunctive symbiotic treatment significantly reduced the percentages of patients with symptoms and endoscopic signs, and diminished inflammatory cells. In conclusion, the present study demonstrates that a symbiotic was able, as adjuvant treatment, to significantly improve symptoms, endoscopic feature, and cytology in patients with INAR, and its effect may be long lasting.

In vitro evidence for efficacy in food intolerance for the multispecies probiotic formulation Ecologic® Tolerance (Syngut™).

The beneficial effects of probiotics are currently the subject of extensive studies in health and medical research. The aim of this research was to specifically design a new probiotic formulation for supplementation in people suffering from food intolerance. The selection of strains was focussed on the capacity to influence mechanisms of action that are important in development of food intolerance with the following parameters measure: in vitro capacity to produce ß-galactosidase, in vitro strengthening of the epithelial barrier, in vitro stimulation of cytokines produced by regulatory T cells, in addition to assessing fundamental quality criteria (stability, gastrointestinal (GI)-survival, multispecies concept, allergen-free). Ecologic®Tolerance/Syngut™ was subsequently developed consisting of a multispecies concept using 4 different probiotic strains (Bifidobacterium lactis W51, Lactobacillus acidophilus W22, Lactobacillus plantarum W21 and Lactococcus lactis W19). Each of these strains demonstrated ability to survive the GI-tract and strain specific effects in producing ß-galactosidase, strengthening the gut barrier function after immunological-induced stress and inhibiting Th2 cytokines (IL-4, IL-5 and IL-13 (≥50%), in addition to stimulating interleukin-10 levels; thus, providing in vitro evidence for the efficacy of the selected strains to provide beneficial effects in patients suffering from food intolerance.

ADMINISTRATION OF EARLY POST-PARTUM ORLAN DRENCH IN DAIRY COWS: EFFECT ON METABOLIC PROFILE / ADMINISTRACIÓN ORAL DE DRENCH EN EL POSPARTO TEMPRANO EN VACAS LECHERAS: EFECTO SOBRE EL PERFIL METABÓLICO

Some prophylactic treatments have been proposed in high-yielding dairy cattle in order to minimize the effects of negative energy balance and some disturbances such as hypocalcaemia and ketosis. The objective of this study was to evaluate the effects of two doses of Drench within 24 h after calving on the metabolic profile and prevention of ketosis. A total of 48 cows from a herd in Rio Grande do Sul state (southern Brazil) was used in the study. The animals were randomly selected and treated orally with Drench (N= 32, propylene glycol, electrolytes and choline in 40 L of water) and water (N= 16) used as control. Blood samples were collected by blood coccygeal venipuncture through a vacutainer plain system tubes. Biochemical determinations were performed in serum (albumin, urea, cholesterol, triglycerides, non-esterified fatty acids -NEFA-, calcium, phosphorus, magnesium, aspartate transaminase -AST- and gammaglutamyl-transferase -GGT-) and a cow-side determination of beta-hydroxybutyrate (BHB) was performed using the Abbot blood Precision Xtra system. All cows in the experiment had their milk production controlled. The Drench treatment produces a tendency to a better milk yield (32.5 vs 29.6 L/cow/day) and helps to prevent subclinical ketosis, as indicated by a lesser prevalence of subclinical ketosis (29.7% vs 37.2%) and mean values of BHB (1.19 vs 1.27 mmol/L) as well as a lesser lipolysis as indicated by NEFA values (509 vs 1.560 pmol/L). The other components of the metabolic profile did not have substantial effects between treatments. In short, on the conditions of the present work, the Drench treatment is an effective management tool for prevention of subclinical ketosis and severe lipolysis.

Alguns tratamentos profiláticos têm sido propostos em vacas leiteiras de alta produção a fim de minimizar os efeitos do balanço energético negativo e alguns distúrbios como hipocalcemia e cetose. Os objetivos desse estudo foram avaliar os efeitos da administração de duas doses de Drench em até 24 h depois do parto sobre o perfil metabólico e a prevenção da cetose. Um grupo de 48 vacas de um rebanho no Rio Grande do Sul foi usado no estudo. Os animais foram selecionados aleatoriamente e tratado oralmente com Drench (N= 32, propileno-glicol, eletrólitos e colina em 40 L de água) e água (N= 16) usado como controle. Amostras de sangue foram coletadas por punção venosa coccígea, através do sistema vacutainer, em tubos sem anticoagulante. Foram realizadas determinações bioquímicas no soro (albumina, ureia, colesterol, triglicerídeos, ácidos graxos não esterificados -NEFA-, cálcio, fósforo, magnésio, aspartato aminotransferase -AST- e gama-glutamil-transferase -GGT-), e na propriedade, ao pé da vaca, foi feita a determinação do beta-hidroxibutirato (BHB) no sangue com o sistema Abbot Precision Xtra. Todas as vacas do experimento tiveram sua produção leiteira controlada. O tratamento com Drench causou tendência a uma melhor produção de leite (32.5 vs 29.6 L/vaca/dia) e ajudou a prevenir a cetose subclínica, como indicou a menor prevalência (29.7% vs 37.2%) e menores médias de BHB (1.19 vs 1.27 mmol/L) bem como menor lipólise, indicado pelos valores de NE FA (509 vs 1.560 μmol/L). Os demais componentes do perfil metabólico não tiveram efeitos substanciais entre os tratamentos. Em suma, nas condições do presente trabalho, o tratamento com Drench pode ser considerado eficaz como ferramenta para a prevenção de cetose subclínica e da lipólise severa.

Low progesterone concentration during the development of the first follicular wave reduces pregnancy per insemination of lactating dairy cows.

Objectives were to determine the effect of progesterone (P4) concentration on fertility of lactating dairy cows induced to ovulate follicles of the first follicular wave. Lactating dairy cows (n=989) at 38±3d postpartum were balanced by parity and body condition score and randomly assigned to 3 treatments: first follicular wave (FFW), first follicular wave with exogenous P4 (FFWP), or second follicular wave (SFW). All cows had their estrous cycle presynchronized with 2 injections of prostaglandin (PG) F(2α) given 14 d apart. Cows in the FFW and FFWP treatments started the ovulation synchronization protocol 3 d after the last PGF(2α) of the presynchronization protocol, whereas SFW cows received a GnRH injection (100 µg of gonadorelin diacetate; Cystorelin, Merial Ltd., Duluth, GA) 3 d after the last PGF(2α) of the presynchronization protocol and started the synchronization protocol 7 d later. The synchronization protocol consisted of GnRH on d -10, PGF(2α) on d -3, and GnRH concurrent with timed artificial insemination (AI) on d 0. Cows in the FFWP treatment received 2 controlled internal drug release inserts containing 1.38 g of P4 from d -8 to -3. Progesterone concentration was determined on d -10, -8, -6, -3, and 0 from all cows and at 7, 14, and 21 d after AI from a subsample of cows (n=170). Cows (n=715) had their ovaries scanned by ultrasound on d -10, -3, and 7 d. Pregnancy was diagnosed at 38 and 66 d after AI. Concentration of P4 from study d -8 to -3 was lowest for FFW cows (1.4±0.1 ng/mL) and similar between SFW (3.7±0.2 ng/mL) and FFWP (3.7±0.1 ng/mL) cows. Diameter of the dominant follicle on study d -3 was greater for FFW cows (16.5±0.3 mm) than for SFW cows (15.4±0.3 mm), but diameter of the dominant follicle of FFWP cows was not different (15.9±0.3 mm) compared with that of SFW and FFW cows. The incidence of multiple ovulation was largest for FFW cows (SFW=19.5, FFW=33.6, FFWP=19.0%), but pregnancy per AI (P/AI) at 66 d was smallest for FFW cows (SFW=38.9, FFW=22.3, FFWP=32.0%). Anovular cows in the SFW (19.4 vs. 42.8%) and FFWP (22.1 vs. 37.2%) treatments had reduced P/AI compared with cyclic cows, despite having similar or greater P4 concentration from study d -8 to -3, respectively. Estrus and ovulation synchronization protocols for lactating dairy cows must result in growth of ovulatory follicle under P4 concentration >2 ng/mL to ensure high P/AI.

Resynchronization strategies to improve fertility in lactating dairy cows utilizing a presynchronization injection of GnRH or supplemental progesterone: I. Pregnancy rates and ovarian responses.

Objectives were to evaluate 3 resynchronization protocols for lactating dairy cows. At 32+/-3 d after pre-enrollment artificial insemination (AI; study d -7), 1 wk before pregnancy diagnosis, cows from 2 farms were enrolled and randomly assigned to 1 of 3 resynchronization protocols after balancing for parity, days in milk, and number of previous AI. All cows were examined for pregnancy at 39+/-3 d after pre-enrollment AI (study d 0). Cows enrolled as controls (n=386) diagnosed not pregnant were submitted to a resynchronization protocol (d 0-GnRH, d 7-PGF2alpha, and d 10-GnRH and AI) on the same day. Cows enrolled in the GGPG (GnRH-GnRH-PGF2alpha-GnRH) treatment (n=357) received a GnRH injection at enrollment (d -7) and if diagnosed not pregnant were submitted to the resynchronization protocol for control cows on d 0. Cows enrolled in CIDR treatment (n=316) diagnosed not pregnant received the resynchronization protocol described for control cows with addition of a controlled internal drug release (CIDR) insert containing progesterone (P4) from d 0 to 7. In a subgroup of cows, ovaries were scanned and blood was sampled for P4 concentration on d 0 and 7. After resynchronized AI, cows were diagnosed for pregnancy at 39+/-3 and 67+/-3 d (California herds) or 120+/-3 d (Arizona herds). Cows in the GGPG treatment had more corpora lutea than CIDR and control cows on d 0 (1.30+/-0.11, 1.05+/-0.11, and 1.05+/-0.11, respectively) and d 7 (1.41+/-0.14, 0.97+/-0.13, and 1.03+/-0.14, respectively). A greater percentage of GGPG cows ovulated to GnRH given on d 0 compared with CIDR and control cows (48.4, 29.6, and 36.6%, respectively), but CIDR and control did not differ. At 39+/-3 d after resynchronized AI, pregnancy per AI (P/AI) was increased in GGPG (33.6%) and CIDR (31.3%) cows compared with control (24.6%) cows. At 67 or 120+/-3 d after resynchronized AI, P/AI of GGPG and CIDR cows was increased compared with control cows (31.2, 29.5, and 22.1%, respectively). Presynchronizing the estrous cycle of lactating dairy cows with a GnRH 7 d before the start of the resynchronization protocol or use of a CIDR insert within the resynchronization protocol resulted in greater P/AI after resynchronized AI compared with control cows.

Sex-sorted semen for dairy heifers: effects on reproductive and lactational performances.

The objectives of this study were to evaluate the effects of using sex-sorted semen for first AI of heifers on health and productivity during first lactation. Holstein heifers (herd A=227 and herd B=1,144) received first artificial insemination (AI) with sex-sorted semen (SX; n=343) or conventional semen (CS; n=1,028), and all heifers that displayed estrus after first AI were reinseminated with conventional semen up to 11 times before being culled. Age at first AI was 13.1+/-0.1 and 13.8+/-0.1 mo for SX and CS heifers, respectively, in herd A and 12.9+/-0.1 mo for both SX and CS heifers in herd B. Pregnancy per AI after first AI was greater for CS heifers than for SX heifers (51.8 vs. 40.2%). From heifers initially enrolled, 70.2% calved in herds A (n=188) or B (n=774) and first-lactation data were collected. Interval from first AI to calving was greater for SX heifers than for CS heifers (10.2+/-0.1 vs. 9.9+/-0.1 mo). Among heifers conceiving to first AI, SX heifers were more likely than CS heifers to deliver a female calf (85.7 vs. 47.7%), but because SX heifers were more likely to deliver a dead calf (8.8 vs. 3.4%), the difference in proportion of SX and CS heifers delivering a live female calf was smaller than expected (SX=79.1%; CS=47.2%). Rearing cost from first AI to calving was greater for SX heifers than for CS heifers ($775.3+/-6.7 vs. $750.0+/-5.9), but calf revenue tended to be greater for SX heifers ($142.0+/-7.2 vs. $126.7+/-6.4) and cost per female calf produced was smaller for SX heifers than for CS heifers ($-809.4+/-10.8 vs. $-1,249.7+/-10.9). Treatment did not affect calving difficulty, proportion of heifers needing assistance, and incidence of retained fetal membranes or metritis. Among heifers that conceived to first AI, however, SX heifers were more likely to be culled within 30 DIM (3.3 vs. 1.6%) and tended to be more likely to be culled within 60 DIM (5.5 vs. 3.4%) than CS heifers, but overall replacement cost was not different ($136.8+/-13.4). Total milk yield (9,245.5+/-84.7 kg) and income over feed cost ($554.7+/-5.1) were not different. Overall economic return was greater for SX heifers than CS heifers ($-83.7+/-36.7 vs. -175.3+/-33.4). Use of sex-sorted semen for first insemination of virgin heifers reduced the cost per female calf produced and increased the economic return during the first lactation.

Neural contractions in colonic strips from patients with diverticular disease: role of endocannabinoids and substance P.

BACKGROUND AND AIMS: Diverticulosis is a common disease of not completely defined pathogenesis. Motor abnormalities of the intestinal wall have been frequently described but very little is known about their mechanisms. We investigated in vitro the neural response of colonic longitudinal muscle strips from patients undergoing surgery for complicated diverticular disease (diverticulitis). METHODS: The neural contractile response to electrical field stimulation of longitudinal muscle strips from the colon of patients undergoing surgery for colonic cancer or diverticulitis was challenged by different receptor agonists and antagonists. RESULTS: Contractions of colonic strips from healthy controls and diverticulitis specimens were abolished by atropine. The beta adrenergic agonist (-) isoprenaline and the tachykinin NK1 receptor antagonist SR140333 had similar potency in reducing the electrical twitch response in controls and diseased tissues, while the cannabinoid receptor agonist (+)WIN 55,212-2 was 100 times more potent in inhibiting contractions in controls (IC50 42 nmol/l) than in diverticulitis strips. SR141716, a selective antagonist of the cannabinoid CB1 receptor, had no intrinsic activity in control preparations but potentiated the neural twitch in diseased tissues by up to 196% in a concentration dependent manner. SR141716 inhibited (+)WIN 55,212-2 induced relaxation in control strips but had no efficacy on (+)WIN 55,212-2 responses in strips from diverticular disease patients. Colonic levels of the endogenous ligand of cannabinoid and vanilloid TRPV1 receptors anandamide were more than twice those of control tissues (54 v 27 pmol/g tissue). The axonal conduction blocker tetrodotoxin had opposite effects in the two preparations, completely inhibiting the contractions of control strips but potentiating those in diverticular preparations, an effect selectively inhibited by SR140333. CONCLUSIONS: Neural control of colon motility is profoundly altered in patients with diverticulitis. Their raised levels of anandamide, apparent desensitisation of the presynaptic neural cannabinoid CB1 receptor, and the SR141716 induced intrinsic response, suggest that endocannabinoids may be involved in the pathophysiology of complications of colonic diverticular disease.

Functional assessment of neuronal cannabinoid receptors in the muscular layers of human ileum and colon.

BACKGROUND & AIMS: The notion that specific receptors account for the ability of natural and synthetic cannabinoids to alter physiological functions, prompted this study aimed at assessing their functional presence in the human gut. METHODS: The effects have been studied of cannabinoids and selective antagonists of their receptors on chemically or electrically evoked contractions in preparations of human intestinal smooth muscle in vitro. RESULTS: Atropine prevented the contractions of longitudinal and circular muscle strips of ileum and colon induced by carbachol or electrical field stimulation; tetrodotoxin abolished only the latter which suggests they do involve activation of cholinergic neurons. The synthetic cannabinoid (+)WIN 55,212-2 had no effect on carbachol contractions, but in a concentration-dependent fashion prevented those elicited by electrical field stimulation - which were insensitive to the putative endogenous cannabinoid anandamide - more potently in longitudinal than in circular strips. The selective CB1 receptor antagonist SR141716, which had no effect in the absence of (+)WIN 55,212-2, competitively antagonised its inhibition of electrical field stimulation contractions, unlike the selective CB2 antagonist SR144528. CONCLUSIONS: Cannabinoid CB1 receptors are functionally present in the human ileum and colon; their pharmacological activation apparently results in inhibition of excitatory cholinergic pathways subserving smooth muscle contraction.

Functional assessment of beta adrenoceptor subtypes in human colonic circular and longitudinal (taenia coli) smooth muscle.

BACKGROUND AND AIMS: The subtype and species related heterogeneity of beta adrenoceptors prompted a functional reappraisal of these molecular targets of motility inhibition in the human colon. METHODS: Relaxation of muscle strips was measured in vitro. RESULTS: The following agonists had decreasing relaxing potency (effective concentration range 10(-8)-10(-4) mol/l): (-)isoprenaline (non-selective), terbutaline (beta(2) selective), CGP 12177 (beta(3) selective, also beta(1), beta(2) antagonist), and SR 58611A (beta(3) selective). Isoprenaline and terbutaline were more potent on circular than taenia strips; CGP 12177 and SR 58611A weakly and partially relaxed taenia but had little effect on circular strips. The potency of isoprenaline on circular strips was greatly reduced by the beta(1) selective antagonist CGP 20712 (10(-7) mol/l), and less so by ICI 118551 (10(-7) mol/l, beta(2) selective). CGP 20712 and ICI 118551 together (both 3 x 10(-6) mol/l) had no effect on taenia relaxation by SR 58611A and rendered isoprenaline and terbutaline virtually inactive on circular strips, although not on taenia, which was relaxed at higher than control concentrations and maximally by isoprenaline. Propranolol, a beta(1), beta(2) non-selective antagonist, at high concentrations (10(-5) mol/l) prevented taenia relaxation by CGP 12177 and SR 58611A; its quantitative antagonism of isoprenaline (in common with that of CGP 12177 used as an antagonist) was competitive in circular strips but not on taenia. CONCLUSIONS: beta(1), beta(2), and beta(3) adrenoceptors are functionally detectable in the human colon; agonist stimulation of any one type relaxed taenia but only isoprenaline was fully effective at the beta(3) subtype.

In vitro functional evidence of different neurotensin-receptors modulating the motor response of human colonic muscle strips.

1. The newly developed non-peptide neurotensin (NT)-receptor antagonists SR 48692 and SR 142948 were used to challenge NT responses of human colonic circular smooth muscle strips in vitro. The presence of NT1 and NT2 receptor transcripts in this tissue was tested by reverse transcriptase polymerase chain reaction (RT - PCR) analysis. 2. NT potently and dose-dependently contracted muscle strips, with significant regional differences in potency and efficacy between the transverse and distal colon: EC50, 3.6 and 7.5 nM; the maximal effect was 70 and 55% of 0.1 mM carbachol. Colonic responses to NT in both segments were virtually the same in the presence of atropine (1 microm), levocabastine (10 microM) or tetrodotoxin (1 microM). 3. SR 142948 (10 nM - 1 microM) competitively antagonized NT responses in the transverse and distal colon with similar affinities: pA2 values 8.71 and 8.45, slopes 0.98 and 0.99. SR 48692 (10 nM - 10 microM) antagonized the NT response competitively in the distal colon (pA2 6.55, slope 0.79) and non-competitively in the transverse colon (pA2 8.0, slope 0.51). Neither compound had any agonist effect. 4. The fact that the specific antagonists prevented NT-evoked atropine- and tetrodotoxin-insensitive mechanical responses of colonic muscle strips is highly consistent with the presence in these tissues of non-neuronal NT receptors, whose heterogeneity in the transverse segment is supported by the non-competitive antagonism of SR 48692. The finding of NT1 receptor transcript in both transverse and distal colon suggests its identity with the lower affinity site disclosed functionally by SR 48692 in these segments.

In vitro functional evidence of neuronal cannabinoid CB1 receptors in human ileum.

We investigated the effect of the cannabinoid agonist (+)WIN-55212-2 on human ileum longitudinal smooth muscle preparations, either electrically stimulated or contracted by carbachol. Electrical field stimulation mostly activated cholinergic neurons, since atropine and tetrodotoxin (TTX), alone or coincubated, reduced twitch responses to a similar degree (85%). (+)WIN-55212-2 concentration-dependently inhibited twitch responses (IC50 73 nM), but had no additive effect with atropine or TTX. The cannabinoid CB1 receptor antagonist SR 141716 (pA2 8.2), but not the CB2 receptor antagonist, SR 144528, competitively antagonized twitch inhibition by (+)WIN-55212-2. Atropine but not (+)WIN-55212-2 or TTX prevented carbachol-induced tonic contraction. These results provide functional evidence of the existence of prejunctional cannabinoid CB1-receptors in the human ileum longitudinal smooth muscle. Agonist activation of these receptors prevents responses to electrical field stimulation, presumably by inhibiting acetylcholine release. SR 141716 is a potent and competitive antagonist of cannabinoid CB1 receptors naturally expressed in the human gut.