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.

We investigated the eect of the cannabinoid agonist (+)WIN-55212-2 on human ileum longitudinal smooth muscle preparations, either electrically stimulated or contracted by carbachol. Electrical ®eld stimulation mostly activated cholinergic neurons, since atropine and tetrodotoxin (TTX), alone or coincubated, reduced twitch responses to a similar degree (85%). (+)WIN-55212-2 concentrationdependently inhibited twitch responses (IC 50 73 nM), but had no additive eect with atropine or TTX. The cannabinoid CB 1 receptor antagonist SR 141716 (pA 2 8.2), but not the CB 2 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 CB 1 -receptors in the human ileum longitudinal smooth muscle. Agonist activation of these receptors prevents responses to electrical ®eld stimulation, presumably by inhibiting acetylcholine release. SR 141716 is a potent and competitive antagonist of cannabinoid CB 1 receptors naturally expressed in the human gut.

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.

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.

The biochemical and pharmacological properties of a novel non-peptide antagonist of the bradykinin (BK) B 1 receptor, SSR240612 [(2R)-2-[((3R)The compound selectivity for B 1 versus B 2 receptors was in the range of 500-to 1000-fold. SSR240612 inhibited Lys 0 -desAr 9 -BK (10 nM)-induced inositol monophosphate formation in human fibroblast MRC5, with an IC 50 of 1.9 nM. It also antagonized des-Arg 9 -BK-induced contractions of isolated rabbit aorta and mesenteric plexus of rat ileum with a pA 2 of 8.9and 9.4, respectively. Antagonistic properties of SSR240612 were also demonstrated in vivo. SSR240612 inhibited desArg 9 -BK-induced paw edema in mice (3 and 10 mg/kg p.o. and 0.3 and 1 mg/kg i.p.). Moreover, SSR240612 reduced capsaicin-induced ear edema in mice (0.3, 3 and 30 mg/kg p.o.) and tissue destruction and neutrophil accumulation in the rat intestine following splanchnic artery occlusion/reperfusion (0.3 mg/kg i.v.). The compound also inhibited thermal hyperalgesia induced by UV irradiation (1 and 3 mg/kg p.o.) and the late phase of nociceptive response to formalin in rats (10 and 30 mg/kg p.o.). Finally, SSR240612 (20 and 30 mg/kg p.o.) prevented neuropathic thermal pain induced by sciatic nerve constriction in the rat. In conclusion, SSR240612 is a new, potent, and orally active specific non-peptide bradykinin B 1 receptor antagonist.Kinins are 9 to 11 amino acid peptides known to be important mediators of pain, inflammation, and cardiovascular homeostasis. They are released in injured tissues from kininogen by activation of plasma or tissue kallikreins (Bhoola et al., 1992). Kinins exert their biological activities via the activation of two subtypes of G-protein coupled receptors, denoted B 1 and B 2 receptors (Regoli and Barabe, 1980;Regoli et al., 1998). Bradykinin (BK) and Lys 0 -BK are natural endogenous agonists of bradykinin B 2 receptors, whereas their kininase I-hydrolyzed metabolites des-Arg 9 -BK and Lys 0 -des-Arg 9 -BK are specific agonists of bradykinin B 1 receptors. B 1 peptide antagonists were obtained by replacing the C-terminal Phe residue of agonists by Leu. Human and rabbit B 1 receptors have a higher affinity for Lys 0 -desArticle, publication date, and citation information can be found at

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.

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 b adrenergic agonist (2) isoprenaline and the tachykinin NK 1 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 CB 1 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 CB 1 receptor, and the SR141716 induced intrinsic response, suggest that endocannabinoids may be involved in the pathophysiology of complications of colonic diverticular disease.

No abstract