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In this chapter, the author discussed the pathophysiology and diagnosis of pulmonary hypertension. The major classifications of pulmonary hypertension are reviewed as well as the current medical management options by pathway effected. The Electrocardiographic and echocardiographic findings in pulmonary hypertension are discussed in relation to severity of illness. The anesthetic considerations necessary in patients with severe pulmonary hypertension are presented.
A reduced protein intake causes a decrease in insulin-like growth factor 1 (IGF1) concentrations and modulates calcium (Ca) homeostasis in young goats. The IGF1 is synthesised by the liver in response to stimulation by growth hormone (GH). Due to rumino-hepatic circulation of urea, ruminants are suitable for investigating the effects of a protein reduction despite sufficient energy intake. The present study aimed to investigate the impact of a protein reduced diet on the expression of components of the somatotropic axis. Male young goats were divided into two feeding groups receiving either a control diet (20% crude protein (CP)) or a reduced protein diet (9% CP). Blood concentrations of IGF1 and GH were measured and a 24-h GH secretion profile was compiled. Moreover, ionised Ca and insulin concentrations as well as mRNA and protein expression levels of hepatic proteins involved in GH signalling were quantified. Due to the protein reduced diet, concentrations of ionised Ca, insulin and IGF1 decreased significantly, whereas GH concentrations remained unchanged. Expression levels of the hepatic GH receptor (GHR) decreased during a protein reduction. The GHR expression was downregulated due to diminished insulin concentrations as both parameters were positively correlated. Insulin itself might be reduced due to reduced blood Ca levels that are involved in insulin release. The protein reduced diet had an impact on the expression of components of the somatotropic axis as a disruption of the GH-IGF1 axis brought about by diminished GHR expression was shown in response to a protein reduced diet.
This study was carried out to delineate differences between MDD and healthy controls in dynorphin and kappa opioid receptor (KOR) levels in association with changes in the β-endorphin – mu opioid receptor (MOR) and immune-inflammatory system
The present study examines dynorphin, KOR, β-endorphin, MOR, interleukin (IL)-6 and IL-10 in 60 drug-free male participants with MDD and 30 age-matched healthy males.
Serum dynorphin, KOR, β-endorphin and MOR are significantly higher in MDD as compared to controls. The increases in the dynorphin/KOR system and β-endorphin/MOR system are significantly intercorrelated and are both strongly associated with increased IL-6 and IL-10 levels. Dynorphin, β-endorphin, KOR and both cytokines showed a good diagnostic performance for MDD versus controls with a bootstrapped (n=2000) area under the receiver operating curve of 0.972. The dynorphin/KOR system is significantly decreased in depression with comorbid nicotine dependence.
Our findings suggest that in MDD, immune activation is associated with a simultaneous activation of dynorphin/KOR and β-endorphin/MOR signaling and that these opioid systems may participate in the pathophysiology of depression by a) exerting immune regulatory activities attenuating the primary immune response; and b) modulating reward responses and mood as well as emotional and behavioral responses to stress.
Encephalitis due to anti-N-methyl-D-Aspartate receptor antibodies (ANMDARE) is the most frequent immune-mediated encephalitis. It is distinguished by the subacute onset of neuropsychiatric symptoms.
To evaluate the characteristic neuropsychiatric symptoms and their outcome in patients diagnosed with anti-NMDAR encephalitis.
This was a prospective, longitudinal study in patients with a diagnostic suspicion of ANMDARE that presented to the National Institute of Neurology from March 2018 to February 2019. A comparative analysis of two groups (positive NMDAR versus negative NMDAR antibodies in cerebrospinal fluid [CSF]) was done on admission and at discharge. Neuropsychiatric systematic assessments included the Neuropsychiatric Inventory Questionnaire, the Bush Francis Catatonia Rating Scale, the Confusion Assessment Method Severity, the Montreal Cognitive Assessment, and the Overt Agitation Severity Scale.
24 individuals were analyzed: 14 had positive NMDAR antibodies, and 10 had negative NMDAR antibodies in CSF. On admission, agitation/aggression, euphoria/exaltation, and disinhibition were more common in patients with positive antibodies. Excited catatonia and delirium were diagnosed more frequently in patients with positive antibodies. At discharge, there was an important decrease in neuropsychiatric symptoms, but substantial cognitive impairment remained. The mean hospitalization length was 41.71 (SD 39.33) days for patients with definitive anti-NMDAR encephalitis (p 0.259).
Neuropsychiatric symptoms profile in ANMDARE was associated with the early onset of euphoria/exaltation and disinhibition, accompanied by marked psychomotor agitation. When ANMDARE was suspected, the presence of excited-type catatonia and delirium showed a tendency to predict definitive ANMDARE. At discharged, most patients recovered from catatonia, delirium, and psychosis, but marked cognitive symptoms, anxiety, and depression persisted at discharge.
Integrins are large heterodimeric type 1 membrane proteins expressed in all nucleated mammalian cells. Eighteen α-chains and eight β-chains can combine to form 24 different integrins. They are cell adhesion proteins, which bind to a large variety of cellular and extracellular ligands. Integrins are required for cell migration, hemostasis, translocation of cells out from the blood stream and further movement into tissues, but also for the immune response and tissue morphogenesis. Importantly, integrins are not usually active as such, but need activation to become adhesive. Integrins are activated by outside-in activation through integrin ligand binding, or by inside-out activation through intracellular signaling. An important question is how integrin activity is regulated, and this topic has recently drawn much attention. Changes in integrin affinity for ligand binding are due to allosteric structural alterations, but equally important are avidity changes due to integrin clustering in the plane of the plasma membrane. Recent studies have partially solved how integrin cell surface structures change during activation. The integrin cytoplasmic domains are relatively short, but by interacting with a variety of cytoplasmic proteins in a regulated manner, the integrins acquire a number of properties important not only for cell adhesion and movement, but also for cellular signaling. Recent work has shown that specific integrin phosphorylations play pivotal roles in the regulation of integrin activity. Our purpose in this review is to integrate the present knowledge to enable an understanding of how cell adhesion is dynamically regulated.
Mastitis, a major infectious disease in dairy cows, is characterized by an inflammatory response to pathogens such as Escherichia coli and Staphylococcus aureus. To better understand the immune and inflammatory response of the mammary gland, we stimulated bovine mammary gland epithelial cells (BMECs) with E. coli-derived lipopolysaccharide (LPS). Using transcriptomic and proteomic analyses, we identified 1019 differentially expressed genes (DEGs, fold change ≥2 and P-value < 0.05) and 340 differentially expressed proteins (DEPs, fold change ≥1.3 and P-value < 0.05), of which 536 genes and 162 proteins were upregulated and 483 genes and 178 proteins were downregulated following exposure to LPS. These differentially expressed genes were associated with 172 biological processes; 15 Gene Ontology terms associated with response to stimulus, 4 associated with immune processes, and 3 associated with inflammatory processes. The DEPs were associated with 51 biological processes; 2 Gene Ontology terms associated with response to stimulus, 1 associated with immune processes, and 2 associated with inflammatory processes. Meanwhile, several pathways involved in mammary inflammation, such as Toll-like receptor, NF-κB, and NOD-like receptor signaling pathways were also represented. NLRP3 depletion significantly inhibited the expression of IL-1β and PTGS2 by blocking caspase-1 activity in LPS-induced BMECs. These results suggest that NLR signaling pathways works in coordination with TLR4/NF-κB signaling pathways via NLRP3-inflammasome activation and pro-inflammatory cytokine secretion in LPS-induced mastitis. The study highlights the function of NLRP3 in an inflammatory microenvironment, making NLRP3 a promising therapeutic target in Escherichia coli mastitis.
Anti-N-methyl-D-aspartate receptor (NMDAr) encephalitis is a relatively recent autoimmune entity, as it was first described in 2007. Given that it is a condition with neuropsychiatric symptoms, its initial symptom is frequently psychiatric in nature. Hence, psychiatrists are often the first physicians to assess these patients and, as so, must recognize this type of encephalitis as a possible cause. Catatonia may be inaugural or develop throughout the course of the disease. Management of patients with anti-NMDAr encephalitis is based on etiologic treatment with immunotherapy and removal of the associated tumor, if any. However, these catatonic patients may have variable responses to etiologic treatment, sometimes with refractory catatonic symptoms, which attests to the necessary urgency to know how to manage these patients. In the clinical setting, physicians appear to be using guidelines originally created to the management of catatonia due to primary psychiatric conditions. In this literature review, catatonia was historically contextualized and anti-NMDAr encephalitis overall described. Finally, catatonia secondary to this type of encephalitis was discussed.
Malnutrition and acute kidney injury (AKI) are common complications in hospitalized patients, and both increase mortality; however, the relationship between them is unknown. This is a retrospective propensity score matching study enrolling 46,549 inpatients, aimed to investigate the association between Nutritional Risk Screening 2002 (NRS-2002) and AKI, and to assess the ability of NRS-2002 and AKI in predicting prognosis. In total, 37,190 (80%) and 9,359 (20%) patients had NRS-2002 scores < 3 and ≥ 3, respectively. Patients with NRS-2002 scores ≥ 3 had longer lengths of stay (12.6±7.8 days vs. 10.4±6.2 days, P < 0.05), higher mortality rates (9.6% vs. 2.5%, P<0.05), and higher incidence of AKI (28% vs. 16%, P < 0.05) than normal nutritional patients. The NRS-2002 showed a strong association with AKI, that is, the risk of AKI changed in parallel with the score of the NRS-2002. In short- and long-term survival, patients with a lower NRS-2002 score or who did not have AKI achieved a significantly lower risk of mortality than those with a high NRS-2002 score or AKI. Univariate Cox regression analyses indicated that both the NRS-2002 and AKI were strongly related to long-term survival (area under the curve (AUC) 0.79 and 0.71) and that the combination of the two showed better accuracy (AUC 0.80) than the individual variables. In conclusion, malnutrition can increase the risk of AKI, and both AKI and malnutrition can worsen the prognosis, that the undernourished patients who develop AKI yield far worse prognosis than normal nutritional patients.
Small intestinal epithelium homeostasis involves four principal cell types: enterocytes, goblet, enteroendocrine and Paneth cells. Epidermal growth factor (EGF) has been shown to affect enterocyte differentiation. This study determined the effect of dietary EGF on goblet, enteroendocrine and Paneth cell differentiation in piglet small intestine and potential mechanisms. Forty-two weaned piglets were used in a 2 × 3 factorial design; the major factors were time post-weaning (days 7 and 14) and dietary treatment (0, 200 or 400 µg/kg EGF supplementation). The numbers of goblet and enteroendocrine cells were generally greater with the increase in time post-weaning. Moreover, the supplementation of 200 µg/kg EGF increased (P < 0.01) the number of goblet and enteroendocrine cells in villus and crypt of the piglet small intestine as compared with the control. Dietary supplementation with 200 µg/kg EGF enhanced (P < 0.05) abundances of differentiation-related genes atonal homologue 1, mucin 2 and intestinal trefoil factor 3 messenger RNA (mRNA) as compared with the control. Piglets fed 200 or 400 µg/kg EGF diet had increased (P < 0.05) abundances of growth factor-independent 1, SAM pointed domain containing ETS transcription factor and pancreatic and duodenal homeobox 1 mRNA, but decreased the abundance (P < 0.01) of E74 like ETS transcription factor 3 mRNA as compared with the control. Animals receiving 400 µg/kg EGF diets had enhanced (P < 0.05) abundances of neurogenin3 and SRY-box containing gene 9 mRNA as compared with the control. The mRNA abundance and protein expression of lysozyme, a marker of Paneth cell, were also increased (P < 0.05) in those animals. As compared with the control, dietary supplementation with 200 µg/kg EGF increased the abundance of EGF receptor mRNA and the ratio of non-phospho(p)-β-catenin/β-catenin (P < 0.05) in villus epithelial cells at days 7 and 14. This ratio in crypt epithelial cells was higher (P < 0.05) on the both 200 and 400 µg/kg EGF groups during the same period. Our results demonstrated that dietary EGF stimulated goblet, enteroendocrine and Paneth cell differentiation in piglets during the post-weaning period, partly through EGFR and Wnt/β-catenin signalling.
5-HT4 receptor stimulation has pro-cognitive and antidepressant-like effects in animal experimental studies; however, this pharmacological approach has not yet been tested in humans. Here we used the 5-HT4 receptor partial agonist prucalopride to assess the translatability of these effects and characterise, for the first time, the consequences of 5-HT4 receptor activation on human cognition and emotion.
Forty one healthy volunteers were randomised, double-blind, to a single dose of prucalopride (1 mg) or placebo in a parallel group design. They completed a battery of cognitive tests measuring learning and memory, emotional processing and reward sensitivity.
Prucalopride increased recall of words in a verbal learning task, increased the accuracy of recall and recognition of words in an incidental emotional memory task and increased the probability of choosing a symbol associated with a high likelihood of reward or absence of loss in a probabilistic instrumental learning task. Thus acute prucalopride produced pro-cognitive effects in healthy volunteers across three separate tasks.
These findings are a translation of the memory enhancing effects of 5-HT4 receptor agonism seen in animal studies, and lend weight to the idea that the 5-HT4 receptor could be an innovative target for the treatment of cognitive deficits associated with depression and other neuropsychiatric disorders. Contrary to the effects reported in animal models, prucalopride did not reveal an antidepressant profile in human measures of emotional processing.
Mixed presentations, defined by simultaneous occurrence of depressive and manic symptoms, are difficult to treat. Antidepressants, although commonly used, have weak evidence of efficacy and may increase risk of mood destabilization. The aim of this pooled post hoc analysis was to evaluate the efficacy of cariprazine in the treatment of bipolar depression with or without concurrent manic symptoms.
Patients from 3 randomized, double-blind, placebo-controlled studies who met DSM-IV-TR or DSM-5 criteria for bipolar I disorder with a current major depressive episode were identified to have concurrent manic symptoms by baseline Young Mania Rating Scale total score ≥4. Efficacy was assessed in cariprazine 1.5 and 3 mg/day dose groups versus placebo; analyses included the least squares mean change from baseline to week 6 in Montgomery-Åsberg Depression Rating Scale (MADRS) total score.
Of 1383 patients randomized to treatment, 808 (58.4%) had concurrent manic symptoms. For patients with manic symptoms, mean reduction in MADRS total score from baseline to week 6 was significantly greater for both cariprazine 1.5 and 3 mg/day compared with placebo, with least squares mean differences (LSMDs) versus placebo of −2.5 (p = .0033) and −2.9 (p = .0010), respectively; for patients without manic symptoms, the LSMD was significant for 1.5 mg/day (−3.3; p = .0008), but not for 3 mg/day (−1.9; p = .0562).
The results of this post hoc analysis suggest that cariprazine may be an appropriate treatment option for patients with bipolar I depression with or without manic symptoms, with higher doses potentially more effective in patients with manic symptoms.
Breast cancer (BC) is a growing public health concern in most developed and developing countries. Since an increasing number of patients with BC are diagnosed before the menopause and premenopausal women show a more aggressive phenotype, there is consistent interest in promoting prevention strategies in order to reduce the incidence of BC in the premenopause. The Mediterranean diet (MD) has been reported to have beneficial effect in terms of cancer prevention. This healthy dietary pattern consists primarily of foods having important antioxidant properties along with a favourable fatty acid profile, all associated with a reduced risk of cancer. Due to the large variability in study subject characteristics, the protective role of the MD on BC still remains controversial and studies that have investigated the association between adherence to the MD and risk of BC in premenopausal women are fewer than those in postmenopausal women. In addition, the possibility that the beneficial effects of the MD are due to a single component or might more probably derive from the synergic effects of all components of the MD remains a scantly explored field. Considering the increased risk of recurrence and mortality rate of BC in premenopausal women as compared with postmenopausal women, the aim of the present report is to provide a general overview of the current evidence on the relationship between BC and the MD specifically in premenopausal women, and to emphasise the potential role of the MD as an effective measure to reduce the risk of developing BC in premenopausal women.
The diagnosis of anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis relies on the detection of NMDAR IgG autoantibodies in the serum or cerebrospinal fluid (CSF) of symptomatic patients. Commercial kits are available that allow NMDAR IgG autoantibodies to be measured in local laboratories. However, the performance of these tests outside of reference laboratories is unknown.
To report an unexpectedly low rate of NMDAR autoantibody detection in serum from patients with anti-NMDAR encephalitis tested using a commercially available diagnostic kit in an exemplar clinical laboratory.
Paired CSF and serum samples from seven patients with definite anti-NMDAR encephalitis were tested for NMDAR IgG autoantibodies using commercially available cell-based assays run according to manufacturer’s recommendations. Rates of autoantibody detection in serum tested at our center were compared with those derived from systematic review and meta-analyses incorporating studies published during or before March 2019.
NMDAR IgG autoantibodies were detected in the CSF of all patients tested at our clinical laboratory but not in paired serum samples. Rates of the detection were lower than those previously reported. A similar association was recognized through meta-analyses, with lower odds of NMDAR IgG autoantibody detection associated with serum testing performed in nonreference laboratories.
Commercial kits may yield lower-than-expected rates of NMDAR IgG autoantibody detection in serum when run in exemplar clinical (nonreference) laboratories. Additional studies are needed to decipher the factors that contribute to lower-than-expected rates of serum positivity. CSF testing is recommended in patients with suspected anti-NMDAR encephalitis.
Maternal high-fat diet (HFD) alters hypothalamic programming and disrupts offspring energy homeostasis in rodents. We previously reported that the loss of ERα signaling partially blocks the effects of maternal HFD in female offspring fed a standard chow diet. In a companion study, we determined if the effects of maternal HFD were magnified by an adult obesogenic diet in our transgenic mouse models. Heterozygous ERα knockout (wild-type (WT)/KO) dams were fed a control breeder chow diet (25% fat) or a semipurified HFD (45% fat) 4 weeks prior to mating with heterozygous males (WT/KO or WT/ knockin) to produce WT, ERα KO, or ERα knockin/knockout (KIKO) (no estrogen response element (ERE) binding) female offspring, which were fed HFD for 20 weeks. Maternal HFD potentiated the effects of adult HFD on KIKO and KO body weight due to increased adiposity and decreased activity. Maternal HFD also produced KIKO females that exhibit KO-like insulin intolerance and impaired glucose homeostasis. Maternal HFD increased plasma interleukin 6 and monocyte chemoattractant protein 1 levels and G6pc and Pepck liver expression only in WT mice. Insulin and tumor necrosis factor α levels were higher in KO offspring from HFD-fed dams. Arcuate and liver expression of Esr1 was altered in KIKO and WT, respectively. These data suggest that loss of ERE-dependent ERα signaling, and not total ERα signaling, sensitizes females to the deleterious influence of maternal HFD on offspring energy and glucose potentially through the control of peripheral inflammation and hypothalamic and liver gene expression. Future studies will interrogate the tissue-specific mechanisms of maternal HFD programming through ERα signaling.
Flaxseed oil is rich in ɑ-linolenic acid (ALA), which is the metabolic precursor of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). This study investigated the effect of flaxseed oil supplementation on lipopolysaccharide (LPS)-induced muscle atrophy and carbohydrate oxidation impairment in a piglet model. Twenty-four weaned pigs were used in a 2 × 2 factorial experiment including dietary treatment (5% corn oil vs. 5% flaxseed oil) and LPS challenge (saline vs. LPS). On day 21 of treatment, the pigs were injected intraperitoneally with 100 μg/kg BW LPS, or sterile saline. At 4 h after injection, blood, gastrocnemius muscle and longissimus dorsi (LD) muscle were collected. Flaxseed oil supplementation increased ALA, EPA, total n-3 polyunsaturated fatty acids contents, protein/DNA ratio, and pyruvate dehydrogenase complex (PDC) quantity in muscles (p<0.05). In addition, flaxseed oil reduced mRNA expression of toll-like receptor (TLR) 4 and nucleotide-binding oligomerization domain protein (NOD) 2 and their downstream signaling molecules in muscles, and decreased plasma concentrations of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-8, and mRNA expression of TNF-α, IL-1β and IL-6 (p<0.05). Moreover, flaxseed oil inclusion increased the ratios of phosphorylated Akt 1/ total Akt 1 and phosphorylated forkhead Box O (FOXO) 1/ total FOXO1, and reduced mRNA expression of FOXO1, muscle RING finger (MuRF) 1, and pyruvate dehydrogenase kinase (PDK) 4 in muscles (p<0.05). These results suggest that flaxseed oil might have a positive effect on alleviating muscle protein loss and carbohydrates oxidation impairment induced by LPS challenge through regulation of TLR4/NOD and Akt/FOXO signaling pathway.
Fatty acid taste (FAT) perception is involved in the regulation of dietary fat intake, where impaired FAT is associated with increased fatty food intake. There are a number of FAT receptors identified on human taste cells that are potentially responsible for FAT perception. Manipulating dietary fat intake, and in turn FAT perception, would elucidate the receptors that are associated with long-term regulation of FAT perception. The present study aimed to assess associations between diet-mediated changes to FAT receptors and FAT perception in humans. A co-twin randomised controlled trial was conducted, where each matching twin within a pair were randomly allocated to either an 8-week low-fat (LF; <20 % energy fat) or an 8-week high-fat (HF; >35 % energy fat) diet. At baseline and week 8, fungiform papillae were biopsied in the fasted state and FAT receptor gene expressions (cluster of differentiation 36 (CD36), free fatty acid receptor 2 (FFAR2), FFAR4, G protein-coupled receptor 84 (GPR84) and a delayed rectifying K+ channel (K+ voltage-gated channel subfamily A member 2; KCNA2)) were measured using RT-PCR; and FAT threshold (FATT) was assessed using three-alternate forced choice methodology. Linear mixed models were fitted, adjusting for correlation between co-twins. Intake was compliant with the study design, with the LF and HF groups consuming 14·8 and 39·9 % energy from fat, respectively. Expression of FFAR4 increased by 38 % in the LF group (P = 0·023; time–diet interaction P = 0·063). ΔFFAR4 (Δ, week 8–baseline) was associated with Δfat intake (g) ( = −159·4; P < 0·001) and ΔFATT ( = −8·8; P = 0·016). In summary, FFAR4 is involved in long-term diet-mediated changes to FAT perception. Manipulating dietary fat intake, and therefore FFAR4 expression, might aid in reducing taste-mediated passive overconsumption of fatty foods.
Psychiatric and neurodegenerative illnesses are characterized by cognitive impairments, in particular deficits in working memory, decision-making, and executive functions including cognitive flexibility. However, the neuropharmacology of these cognitive functions is poorly understood. The serotonin (5-HT) 2A receptor might be a promising candidate for the modulation of cognitive processes. However, pharmacological studies investigating the role of this receptor system in humans are rare. Recent evidence demonstrates that the effects of Lysergic acid diethylamide (LSD) are mediated via agonistic action at the 5-HT2A receptor. Yet, the effects of LSD on specific cognitive domains using standardized neuropsychological test have not been studied.
We examined the acute effects of LSD (100 µg) alone and in combination with the 5-HT2A antagonist ketanserin (40 mg) on cognition, employing a double-blind, randomized, placebo-controlled, within-subject design in 25 healthy participants. Executive functions, cognitive flexibility, spatial working memory, and risk-based decision-making were examined by the Intra/Extra-Dimensional shift task (IED), Spatial Working Memory task (SWM), and Cambridge Gambling Task (CGT) of the Cambridge Neuropsychological Test Automated Battery.
Compared to placebo, LSD significantly impaired executive functions, cognitive flexibility, and working memory on the IED and SWM, but did not influence the quality of decision-making and risk taking on the CGT. Pretreatment with the 5-HT2A antagonist ketanserin normalized all LSD-induced cognitive deficits.
The present findings highlight the role of the 5-HT2A receptor system in executive functions and working memory and suggest that specific 5-HT2A antagonists may be relevant for improving cognitive dysfunctions in psychiatric disorders.
As the precursor to NAD+ and NADP+, niacin is important for catabolic and anabolic redox reactions. In addition, niacin is known for its anti-lipolytic action via a hydroxycarboxylic acid-2-receptor-dependent mechanism. The anti-lipolytic effects of traditional free niacin supplementation during transition periods had been studied extensively, but the reported effects are ambiguous. In the past decade, a series of studies were conducted to evaluate the effects of rumen-protected niacin (RPN) on production performance and metabolic status in early lactation and on heat stress in dairy cows. Feeding RPN seems more effective than free niacin regarding increasing circulating niacin concentration. The rebound of plasma NEFA was found after termination of niacin abomasal infusion. Feeding RPN or infusion of niacin via the abomasum could suppress lipolysis and reduce insulin resistance in early lactation. Additionally, RPN supplementation could possibly relieve heat stress through vasodilation during moderate to severe heat stress condition. However, these beneficial effects of niacin supplementation have not always been observed. The inconsistent results across studies may be related to dosages of niacin supplementation, rebound of plasma NEFA concentration, stage of lactation or severity of heat stress. Overall, the current review is to present updated information on niacin nutrition in dairy cows and the recommendations are given for future research.
Atlantic salmon (Salmo salar) possess enzymes required for the endogenous biosynthesis of n-3 long-chain PUFA (LC-PUFA), EPA and DHA, from α-linolenic acid (ALA). Linoleic acid (LA) competes with ALA for LC-PUFA biosynthesis enzymes leading to the production of n-6 LC-PUFA, including arachidonic acid (ARA). We aimed to quantify the endogenous production of EPA and DHA from ALA in salmon fed from first feeding on diets that contain no EPA and DHA and to determine the influence of dietary LA and ALA:LA ratio on LC-PUFA production. Salmon were fed from first feeding for 22 weeks with three diets formulated with linseed and sunflower oils to provide ALA:LA ratios of approximately 3:1, 1:1 and 1:3. Endogenous production of n-3 LC-PUFA was 5·9, 4·4 and 2·8 mg per g fish and that of n-6 LC-PUFA was 0·2, 0·5 and 1·4 mg per g fish in salmon fed diets with ALA:LA ratios of 3:1, 1:1 and 1:3, respectively. The ratio of n-3:n-6 LC-PUFA production decreased from 27·4 to 2·0, and DHA:EPA ratio increased and EPA:ARA and DHA:ARA ratios decreased, as dietary ALA:LA ratio decreased. In conclusion, with a dietary ALA:LA ratio of 1, salmon fry/parr produced about 28 μg n-3 LC-PUFA per g fish per d, with a DHA:EPA ratio of 3·4. Production of n-3 LC-PUFA exceeded that of n-6 LC-PUFA by almost 9-fold. Reducing the dietary ALA:LA ratio reduced n-3 LC-PUFA production and EPA:ARA and DHA:ARA ratios but increased n-6 LC-PUFA production and DHA:EPA ratio.
The long-term cholesterol-lowering effect of replacing intake of SFA with PUFA is well established, but has not been fully explained mechanistically. We examined the postprandial response of meals with different fat quality on expression of lipid genes in peripheral blood mononuclear cells (PBMC) in subjects with and without familial hypercholesterolaemia (FH). Thirteen subjects with FH (who had discontinued lipid-lowering treatment ≥4 weeks prior to both test days) and fourteen normolipidaemic controls were included in a randomised controlled double-blind crossover study with two meals, each with 60 g of fat either mainly SFA (about 40% energy) or n-6 PUFA (about 40% energy). PBMC were isolated in fasting, and 4 and 6 h postprandial blood samples. Expression of thirty-three lipid genes was analysed by reverse transcription quantitative PCR. A linear mixed model was used to assess postprandial effects between meals and groups. There was a significant interaction between meal and group for MSR1 (P = 0·03), where intake of SFA compared with n-6 PUFA induced a larger reduction in gene expression in controls only (P = 0·01). Intake of SFA compared with n-6 PUFA induced larger reductions in gene expression levels of LDLR and FADS1/2, smaller increases of INSIG1 and FASN, and larger increases of ABCA1 and ABCG1 (P = 0·01 for all, no group interaction). Intake of SFA compared with n-6 PUFA induced changes in gene expression of cholesterol influx and efflux mediators in PBMC including lower LDLR and higher ABCA1/G1, potentially explaining the long-term cholesterol-raising effect of a high SFA intake.