ADmINIsTRATION Of EARly POsT-PARTum ORAl DRENCh IN DAIRy COws: EffECT ON mETAbOlIC PROfIlE

AbsTRACT 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 gammaglutamyltransferase -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 µmol/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. Key-words: beta-hydroxybutyrate, ketosis, neFa, prevention

A new role for the P2Y-like GPR17 receptor in the modulation of multipotency of oligodendrocyte precursor cells in vitro

Oligodendrocyte precursor cells (OPCs, also called NG2 cells) are scattered throughout brain parenchyma, where they function as a reservoir to replace lost or damaged oligodendrocytes, the myelin-forming cells. The hypothesis that, under some circumstances, OPCs can actually behave as multipotent cells, thus generating astrocytes and neurons as well, has arisen from some in vitro and in vivo evidence, but the molecular pathways controlling this alternative fate of OPCs are not fully understood. Their identification would open new opportunities for neuronal replace strategies, by fostering the intrinsic ability of the brain to regenerate. Here, we show that the anti-epileptic epigenetic modulator valproic acid (VPA) can promote the generation of new neurons from NG2+ OPCs under neurogenic protocols in vitro, through their initial de-differentiation to a stem cell-like phenotype that then evolves to \u201chybrid\u201d cell population, showing OPC morphology but expressing the neuronal marker \u3b2III-tubulin and the GPR17 receptor, a key determinant in driving OPC transition towards myelinating oligodendrocytes. Under these conditions, the pharmacological blockade of the P2Y-like receptor GPR17 by cangrelor, a drug recently approved for human use, partially mimics the effects mediated by VPA thus accelerating cells\u2019 neurogenic conversion. These data show a co-localization between neuronal markers and GPR17 in vitro, and suggest that, besides its involvement in oligodendrogenesis, GPR17 can drive the fate of neural precursor cells by instructing precursors towards the neuronal lineage. Being a membrane receptor, GPR17 represents an ideal \u201cdruggable\u201d target to be exploited for innovative regenerative approaches to acute and chronic brain diseases

A multi-element psychosocial intervention for early psychosis (GET UP PIANO TRIAL) conducted in a catchment area of 10 million inhabitants: study protocol for a pragmatic cluster randomized controlled trial

Multi-element interventions for first-episode psychosis (FEP) are promising, but have mostly been conducted in non-epidemiologically representative samples, thereby raising the risk of underestimating the complexities involved in treating FEP in 'real-world' services

pH-Driven Conformational Switching of Quinoxaline Cavitands in Polymer Matrices

While pH-driven interconversion of tetraquinoxaline cavitands (QxCav) from vase to kite conformation has been extensively studied both in solution and at interfaces, cavitands behavior in solid matrices is still unexplored. Therefore, the synthesis of a new class of quinoxaline cavitand based copolymers is here reported; a soluble linear poly(butyl methacrylate) (PBMA) and an insoluble cross-linked polydimethylsiloxane (PDMS), ensuring a convenient incorporation of the switchable unit, were chosen as polymer matrices. Conformational studies, performed both in solution and at the solid state, confirmed the retention of vase → kite switching behavior when moving from monomeric units to polymeric structures

Effects of a synbiotic formula on functional bowel disorders and gut microbiota profile during long-term home enteral nutrition (Lthen): A pilot study

Long-term enteral nutrition (LTEN) can induce gut microbiota (GM) dysbiosis and gastrointestinal related symptoms, such as constipation or diarrhoea. To date, the treatment of constipation is based on the use of laxatives and prebiotics. Only recently have probiotics and synbiotics been considered, the latter modulating the GM and regulating intestinal functions. This randomized open-label intervention study evaluated the effects of synbiotic treatment on the GM profile, its functional activity and on intestinal functions in long-term home EN (LTHEN) patients. Twenty LTHEN patients were recruited to take enteral formula plus one sachet/day of synbiotic (intervention group, IG) or enteral formula (control group, CG) for four months and evaluated for constipation, stool consistency, and GM and metabolite profiles. In IG patients, statistically significant reduction of constipation and increase of stool consistency were observed after four months (T1), compared to CG subjects. GM ecology analyses revealed a decrease in the microbial diversity of both IC and CG groups. Biodiversity increased at T1 for 5/11 IG patients and Methanobrevibacter was identified as the biomarker correlated to the richness increase. Moreover, the increase of short chain fatty acids and the reduction of harmful molecules have been correlated to synbiotic administration. Synbiotics improve constipation symptoms and influences Methanobrevibacter growth in LTHEN patients

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

BACKGROUND AND AIMS—The subtype and species related heterogeneity of β 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 (β(2) selective), CGP 12177 (β(3) selective, also β(1), β(2) antagonist), and SR 58611A (β(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 β(1) selective antagonist CGP 20712 (10(−7) mol/l), and less so by ICI 118551 (10(−7) mol/l, β(2) selective). CGP 20712 and ICI 118551 together (both 3×10(-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 β(1), β(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—β(1), β(2), and β(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 β(3) subtype.


Keywords: β adrenoceptor subtypes; human colon; smooth muscle; taenia col

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 β adrenergic agonist (−) 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