Development of an efficient method for obtaining lactose and lactulose from whey

Taking into account a wide range of lactulose application in pharmaceutics, baby food production and other fields, along with the importance of technological solutions for its extraction from milk whey, the presented work was carried out to obtain lactulose in one cycle with simultaneous alkaline treatment and desalting of whey by the electromembrane method. Based on the data obtained, an effective method for obtaining a protein concentrate, lactose, and its isomer – lactulose from whey has been developed. The processes of pre-treatment and desalting of milk whey by the electromembrane method were studied and the optimal parameters for the processes implementation were determined. The curves of changes in the concentration of inorganic ions in whey in the desalination process, depending on the degree of demineralization, were plotted

May Measurement Month 2018: a pragmatic global screening campaign to raise awareness of blood pressure by the International Society of Hypertension

Aims Raised blood pressure (BP) is the biggest contributor to mortality and disease burden worldwide and fewer than half of those with hypertension are aware of it. May Measurement Month (MMM) is a global campaign set up in 2017, to raise awareness of high BP and as a pragmatic solution to a lack of formal screening worldwide. The 2018 campaign was expanded, aiming to include more participants and countries. Methods and results Eighty-nine countries participated in MMM 2018. Volunteers (≥18 years) were recruited through opportunistic sampling at a variety of screening sites. Each participant had three BP measurements and completed a questionnaire on demographic, lifestyle, and environmental factors. Hypertension was defined as a systolic BP ≥140 mmHg or diastolic BP ≥90 mmHg, or taking antihypertensive medication. In total, 74.9% of screenees provided three BP readings. Multiple imputation using chained equations was used to impute missing readings. 1 504 963 individuals (mean age 45.3 years; 52.4% female) were screened. After multiple imputation, 502 079 (33.4%) individuals had hypertension, of whom 59.5% were aware of their diagnosis and 55.3% were taking antihypertensive medication. Of those on medication, 60.0% were controlled and of all hypertensives, 33.2% were controlled. We detected 224 285 individuals with untreated hypertension and 111 214 individuals with inadequately treated (systolic BP ≥ 140 mmHg or diastolic BP ≥ 90 mmHg) hypertension. Conclusion May Measurement Month expanded significantly compared with 2017, including more participants in more countries. The campaign identified over 335 000 adults with untreated or inadequately treated hypertension. In the absence of systematic screening programmes, MMM was effective at raising awareness at least among these individuals at risk

Specific behavioral and cellular adaptations induced by chronic morphine are reduced by dietary omega-3 polyunsaturated fatty acids

Opiates, one of the oldest known drugs, are the benchmark for treating pain. Regular opioid exposure also induces euphoria making these compounds addictive and often misused, as shown by the current epidemic of opioid abuse and overdose mortalities. In addition to the effect of opioids on their cognate receptors and signaling cascades, these compounds also induce multiple adaptations at cellular and behavioral levels. As omega-3 polyunsaturated fatty acids (n-3 PUFAs) play a ubiquitous role in behavioral and cellular processes, we proposed that supplemental n-3 PUFAs, enriched in docosahexanoic acid (DHA), could offset these adaptations following chronic opioid exposure. We used an 8 week regimen of n-3 PUFA supplementation followed by 8 days of morphine in the presence of this diet. We first assessed the effect of morphine in different behavioral measures and found that morphine increased anxiety and reduced wheel-running behavior. These effects were reduced by dietary n-3 PUFAs without affecting morphine-induced analgesia or hyperlocomotion, known effects of this opiate acting at mu opioid receptors. At the cellular level we found that morphine reduced striatal DHA content and that this was reversed by supplemental n-3 PUFAs. Chronic morphine also increased glutamatergic plasticity and the proportion of Grin2B-NMDARs in striatal projection neurons. This effect was similarly reversed by supplemental n-3 PUFAs. Gene analysis showed that supplemental PUFAs offset the effect of morphine on genes found in neurons of the dopamine receptor 2 (D2)-enriched indirect pathway but not of genes found in dopamine receptor 1(D1)-enriched direct-pathway neurons. Analysis of the D2 striatal connectome by a retrogradely transported pseudorabies virus showed that n-3 PUFA supplementation reversed the effect of chronic morphine on the innervation of D2 neurons by the dorsomedial prefontal and piriform cortices. Together these changes outline specific behavioral and cellular effects of morphine that can be reduced or reversed by dietary n-3 PUFAs

Select G-Protein-Coupled Receptors Modulate Agonist-Induced Signaling via a ROCK, LIMK, and β-Arrestin 1 Pathway

G-protein-coupled receptors (GPCRs) are typically present in a basal, inactive state but, when bound to an agonist, activate downstream signaling cascades. In studying arrestin regulation of opioid receptors in dorsal root ganglia (DRG) neurons, we find that agonists of delta opioid receptors (δORs) activate cofilin through Rho-associated coiled-coil-containing protein kinase (ROCK), LIM domain kinase (LIMK), and β-arrestin 1 (β-arr1) to regulate actin polymerization. This controls receptor function, as assessed by agonist-induced inhibition of voltage-dependent Ca2+ channels in DRGs. Agonists of opioid-receptor-like receptors (ORL1) similarly influence the function of this receptor through ROCK, LIMK, and β-arr1. Functional evidence of this cascade was demonstrated in vivo, where the behavioral effects of δOR or ORL1 agonists were enhanced in the absence of β-arr1 or prevented by inhibiting ROCK. This pathway allows δOR and ORL1 agonists to rapidly regulate receptor function

Specific behavioral and cellular adaptations induced by chronic morphine are reduced by dietary omega-3 polyunsaturated fatty acids.

Opiates, one of the oldest known drugs, are the benchmark for treating pain. Regular opioid exposure also induces euphoria making these compounds addictive and often misused, as shown by the current epidemic of opioid abuse and overdose mortalities. In addition to the effect of opioids on their cognate receptors and signaling cascades, these compounds also induce multiple adaptations at cellular and behavioral levels. As omega-3 polyunsaturated fatty acids (n-3 PUFAs) play a ubiquitous role in behavioral and cellular processes, we proposed that supplemental n-3 PUFAs, enriched in docosahexanoic acid (DHA), could offset these adaptations following chronic opioid exposure. We used an 8 week regimen of n-3 PUFA supplementation followed by 8 days of morphine in the presence of this diet. We first assessed the effect of morphine in different behavioral measures and found that morphine increased anxiety and reduced wheel-running behavior. These effects were reduced by dietary n-3 PUFAs without affecting morphine-induced analgesia or hyperlocomotion, known effects of this opiate acting at mu opioid receptors. At the cellular level we found that morphine reduced striatal DHA content and that this was reversed by supplemental n-3 PUFAs. Chronic morphine also increased glutamatergic plasticity and the proportion of Grin2B-NMDARs in striatal projection neurons. This effect was similarly reversed by supplemental n-3 PUFAs. Gene analysis showed that supplemental PUFAs offset the effect of morphine on genes found in neurons of the dopamine receptor 2 (D2)-enriched indirect pathway but not of genes found in dopamine receptor 1(D1)-enriched direct-pathway neurons. Analysis of the D2 striatal connectome by a retrogradely transported pseudorabies virus showed that n-3 PUFA supplementation reversed the effect of chronic morphine on the innervation of D2 neurons by the dorsomedial prefontal and piriform cortices. Together these changes outline specific behavioral and cellular effects of morphine that can be reduced or reversed by dietary n-3 PUFAs

Specific behavioral and cellular adaptations induced by chronic morphine are reduced by dietary omega-3 polyunsaturated fatty acids

<div><p>Opiates, one of the oldest known drugs, are the benchmark for treating pain. Regular opioid exposure also induces euphoria making these compounds addictive and often misused, as shown by the current epidemic of opioid abuse and overdose mortalities. In addition to the effect of opioids on their cognate receptors and signaling cascades, these compounds also induce multiple adaptations at cellular and behavioral levels. As omega-3 polyunsaturated fatty acids (n-3 PUFAs) play a ubiquitous role in behavioral and cellular processes, we proposed that supplemental n-3 PUFAs, enriched in docosahexanoic acid (DHA), could offset these adaptations following chronic opioid exposure. We used an 8 week regimen of n-3 PUFA supplementation followed by 8 days of morphine in the presence of this diet. We first assessed the effect of morphine in different behavioral measures and found that morphine increased anxiety and reduced wheel-running behavior. These effects were reduced by dietary n-3 PUFAs without affecting morphine-induced analgesia or hyperlocomotion, known effects of this opiate acting at mu opioid receptors. At the cellular level we found that morphine reduced striatal DHA content and that this was reversed by supplemental n-3 PUFAs. Chronic morphine also increased glutamatergic plasticity and the proportion of Grin2B-NMDARs in striatal projection neurons. This effect was similarly reversed by supplemental n-3 PUFAs. Gene analysis showed that supplemental PUFAs offset the effect of morphine on genes found in neurons of the dopamine receptor 2 (D2)-enriched indirect pathway but not of genes found in dopamine receptor 1(D1)-enriched direct-pathway neurons. Analysis of the D2 striatal connectome by a retrogradely transported pseudorabies virus showed that n-3 PUFA supplementation reversed the effect of chronic morphine on the innervation of D2 neurons by the dorsomedial prefontal and piriform cortices. Together these changes outline specific behavioral and cellular effects of morphine that can be reduced or reversed by dietary n-3 PUFAs.</p></div

Beta-arrestin 1 regulation of reward-motivated behaviors and glutamatergic function

<div><p>The two highly homologous non-visual arrestins, beta-arrestin 1 and 2, are ubiquitously expressed in the central nervous system, yet knowledge of their disparate roles is limited. While beta-arrestin 2 (βarr2) has been implicated in several aspects of reward-related learning and behavior, very little is known about the behavioral function of beta-arrestin 1 (βarr1). Using mice lacking βarr1, we focused on the role of this scaffolding and signal transduction protein in reward-motivated behaviors and in striatal glutamatergic function. We found that βarr1 KO mice were both slower in acquiring cocaine self-administration and in extinguishing this behavior. They also showed deficits in learning tasks supported by a natural food reward, suggesting a general alteration in reward processing. We then examined glutamatergic synaptic strength in WT and KO medium spiny neurons (MSNs) of the Nucleus Accumbens (NAc) shell in naïve animals, and from those that underwent cocaine self-administration. An increase in the AMPA/NMDA (A/N) ratio and a relative lack of GluN2B-enriched NMDARs was found in naïve KO vs WT MSNs. Applying Lim Domain Kinase (LIMK1), the kinase that phosphorylates and inactivates cofilin, to these cells, showed that both βarr1 and LIMK regulate the A/N ratio and GluN2B-NMDARs. Cocaine self-administration increased the A/N ratio and GluN2B-NMDARs in WT MSNs and, although the A/N ratio also increased in KO MSNs, this was accompanied by fewer GluN2B-NMDARs and an appearance of calcium-permeable AMPARs. Finally, to examine the consequences of reduced basal GluN2B-NMDARs in reward-processing seen in KO mice, we chronically infused ifenprodil, a GluN2B antagonist, into the NAc shell of WT mice. This intervention substantially reduced food-motivated behavior. Together these findings identify a previously unknown role of βarr1 in regulating specific reward-motivated behaviors and glutamatergic function.</p></div