Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The influence of N-ethylmaleimide (NEM) on contractions due to exogenously applied noradrenaline and bethanechol and on the inhibitory effects of clonidine, of the enkephalin derivative, FK 33-824, and 2-chloroadenosine (2-CLA) on field stimulation-response curves and [3H]noradrenaline [( 3H]NA) release was studied in the isolated mouse vas deferens. Exposure to NEM (60 microM: 10 min) caused a 30% reduction of the maximal contraction due to NA but nearly abolished the response to bethanechol. NEM partially reversed the depression of the pulse width-response curves by clonidine and FK 33-824 but was without effect with 2-CLA. The contractions evoked by stimulation frequencies above 20 Hz were depressed by NEM both in presence and absence of the agonists. NEM diminished the inhibition of the stimulation-evoked release of [3H]NA by the three agonists. The prejunctional effect of NEM was markedly influenced by the stimulation parameters. These findings support the suggestion that the inhibition mediated by alpha 2-adrenoceptors, mu- and P1-receptors in the mouse vas deferens is NEM-sensitive and possibly transmitted by a pertussis toxin-sensitive G-protein.
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PMID:Pre- and postjunctional effects of N-ethylmaleimide in the isolated mouse vas deferens. 232 59

GPA1734, an inhibitor of BM collagen biosynthesis, was investigated in the CAM model system for its effect on angiogenesis. Evaluation of angiogenesis was performed by placing a thin plastic coverslip inscribed with concentric circles on the CAM and counting the number of vessels intercepting the circles. The rate of BM collagen biosynthesis was monitored using [U-14C] proline incorporation into CAM proteins and determining the collagenase-digestible protein fraction. A marked depression in the vascular density was observed in the CAM area under a plastic disc containing GPA1734 as compared to control discs placed on the CAM about 1 cm apart from days 9 to 12 of incubation. A concomitant decrease in collagenous protein biosynthesis was observed in the area under the discs containing GPA1734 and [U-14C]proline as compared to control discs containing only the radiolabeled proline. The forementioned effects of GPA1734 on CAM were specific because no similar effects were observed with a closely related compound, 9,10-dihydroxy-7-methyl-benzo[b]quinolizinium bromide or with GPA1734 plus Fe++, which did not affect the rate of BM collagen biosynthesis. These results suggest that inhibitors of BM collagen biosynthesis prevent angiogenesis by interfering with the formation of an essential component of the vessel wall. The search for such inhibitors may be a new approach in the development of antiangiogenic agents.
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PMID:Inhibition of basement membrane biosynthesis prevents angiogenesis. 245 Feb 2

Sections of 18 malaria-infected placentas were stained with haematoxylin and eosin, periodic acid and methenamine silver, and immunohistochemically with monoclonal antibodies against human common leukocyte antigen, CLA (CD 45), B cells (CD 20, L 26), T cells (CD 45RO, UCHL-1) and collagen IV. Parasitized erythrocytes accumulated in the maternal villous spaces, with none in the foetal circulation. These were found in association with inflammatory leukocytes and pigments. Fibrinoid necrosis was more prevalent in the heavily infected placentas. Thickening and reduplication of foetal capillary basement membranes, and a decrease in leukocytes, including B and T cells, were seen in the heavily infected placentas. These findings are in keeping with previously reported depression of cellular and humoral immunity in patients with heavy parasitaemia.
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PMID:A histological and immunohistological study of malarial placentas. 853 33

CLA refers to isomers of octadecadienoic acid with conjugated double bonds. The most abundant form of CLA (rumenic acid (RA): c9,t11-18:2) is found in milk and beef fat. Further, CLA supplements containing RA and t10,c12-18:2 are now available. Consumption of commercially produced CLA has been shown to decrease adipose accretion in growing laboratory and production animals and cause milk fat depression in cows. We tested the hypothesis that CLA supplementation would increase milk CLA concentration and decrease milk fat content in humans. Breastfeeding women (n = 9) participated in this double-blind, placebo-controlled, crossover study divided into three periods: intervention I (5 d), washout (7 d), and intervention II (5 d). Women were randomized to treatment order. During each intervention period, women consumed 1.5 g of CLA supplement or placebo (olive oil) daily; during the washout period, no supplements were consumed. Milk was collected by complete breast expression on the final day of each period; milk output was estimated by 24-h weighing on the penultimate day of each intervention period. Milk RA and t10,c12-18:2 concentrations were greater (P < 0.05) during the CLA treatment period as compared to the placebo period. Milk fat content was significantly lower during the CLA treatment, as compared to the placebo treatment (P < 0.05). Data indicate no effect of treatment on milk output. Therefore, it would be prudent that lactating women not consume commercially available CLA supplements at this time.
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PMID:Maternal supplementation with CLA decreases milk fat in humans. 1190 5

Outcome studies examining the efficacy of CAM among people living with HIV-AIDS are often conducted among small sample sizes with very little follow-up data or time points. Generalizability of many of the study findings is further limited by participant attrition. It is difficult to conduct clinical studies on chronically ill patients without participants dropping out, typically because the study demands coupled with their illness become too burdensome. Several studies have been conducted that include control groups, double-blind designs, and randomization. These scientifically sound studies have demonstrated promising results that strongly indicate a need for further research with larger samples in a prospective research design so that safety and efficacy can be determined over time. Many of the studies with small sample sizes reported trends, but did not find statistical significance. Increasing sample sizes in future studies is necessary to evaluate the scientific merit of these trends. Moreover, researchers need to evaluate the clinical and statistical significance in CAM use. The psychologic benefits of taking CAM should not be underestimated. For the purposes of this article, the authors did not include psychologic outcomes; however, there is evidence suggesting that decreasing depression can decrease HIV-related somatic complaints [69]. Studies need also to examine the effectiveness of CAM on psychologic outcomes and physical outcomes. This article and the authors' own research (Gore-Felton C et al, unpublished data) have revealed a high prevalence of alternative supplement use in conjunction with HIV medication, indicating an urgent need to understand the health benefits and the health risks of alternative supplements among patients with HIV and AIDS. Patients and physicians need more empirically based research to examine the toxicities, interactions, and health benefits of CAM. Many patients do not report the use of CAM to their physicians and very few physicians record treatments in the clinical record [70]. This will likely change as CAM becomes more widely recognized as a legitimate medical intervention; however, controlled outcome studies among large, diverse samples of people living with HIV-AIDS are needed. Health care providers need to assess the use of herbal and alternative therapy practices by their patients. Some patients may not be aware that they are taking a supplement or plant-based herb. Furthermore, some patients may believe that they are using something innocuous and even healthy simply because it came from a health food store. Understanding the contraindications of alternative therapies is necessary to prevent deleterious outcomes and to facilitate the safe and efficacious use of CAM in the management of HIV disease and related symptoms. As the epidemic in the United States continues to rise among women and minority populations, clinical research trials must include ethnically diverse patient populations that are gender balanced. Current available studies indicate that many CAM interventions may improve the quality of life of people living with HIV-AIDS; however, further studies using longitudinal, controlled designs are needed to accurately assess the safety of such interventions.
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PMID:HIV: effectiveness of complementary and alternative medicine. 1239 16

CLA is a potent inhibitor of milk fat synthesis, as shown by investigations using mixtures of CLA isomers in FFA form. However, methyl esters of CLA can be initially formed in commercial synthesis, and their use in a supplement has certain manufacturing and cost advantages. Our objective was to compare abomasal infusion of methyl esters of CLA (ME-CLA) and FFA of CLA (FFA-CLA) on milk fat synthesis. Data were also combined with previous investigations to examine broader relationships between trans-10,cis-12 CLA and the reduction in milk fat. Three mid-lactation, rumen-fistulated Holstein cows were used in a 3 x 3 Latin square design. Treatments were (i) control, (ii) ME-CLA, and (iii) FFA-CLA. The ME-CLA and FFA-CLA treatments (4.2 g/d trans-10,cis-12 CLA) resulted in a comparable reduction in milk fat yield (38 and 39%, respectively) and pattern of reduction in individual FA. In contrast, milk yield, milk protein, and feed intake were unaltered by CLA treatment. Combining data across studies revealed strong correlations relating the reduction in milk fat yield to abomasal dose of trans-10,cis-12 CLA (R2 = 0.86), milk fat content of trans-10,cis-12 CLA (R2 = 0.93), and milk fat secretion of trans-10,cis-12 CLA (R2 = 0.82). Across studies, transfer efficiency of abomasally infused trans-10,cis-12 CLA into milk fat was relatively constant (22%; R2 = 0.94). Overall, ME-CLA and FFA-CLA were equally potent in reducing milk fat, and either form could be used to formulate a dietary supplement that would induce milk fat depression.
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PMID:Effect of CLA on milk fat synthesis in dairy cows: comparison of inhibition by methyl esters and free fatty acids, and relationships among studies. 1535 24

The trans-10, cis-12 CLA isomer has been causally related to milk fat depression in dairy cows, although no molecular mechanism has been established. Sterol response element-binding protein (SREBP)-1 is a transcription factor synthesized and retained as a membrane-bound precursor in the endoplasmic reticulum and proteolytically cleaved to release an active fragment that migrates to the nucleus to stimulate lipogenic gene transcription. Certain lipid molecules (i.e., PUFA) were shown to inhibit the proteolytic activation of SREBP-1 in rodent liver models, although there has been no previous demonstration of its presence in bovine tissues or in mammary tissue of any species. We used a bovine mammary cell line (MAC-T) to assess the involvement of SREBP-1 in the regulation of lipid synthesis in bovine mammary cells by trans-10, cis-12 CLA. Treatment with 75 micromol/L trans-10, cis-12 CLA for 48 h resulted in an approximately 50% reduction of (14)C-acetate incorporation into total lipid and corresponding reductions in mRNA abundance for acetyl CoA carboxylase, fatty acid synthase, and stearoyl CoA desaturase, whereas cis-9, trans-11 CLA had no effect on these genes. There was no reduction in SREBP-1 mRNA or precursor protein, but the abundance of the activated nuclear fragment of the protein was significantly reduced by treatment with 75 micromol/L trans-10, cis-12 CLA. These results indicate that trans-10, cis-12 CLA reduces lipid synthesis in the bovine mammary gland through inhibition of the proteolytic activation of SREBP-1 and subsequent reduction in transcriptional activation of lipogenic genes.
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PMID:The inhibitory effect of trans-10, cis-12 CLA on lipid synthesis in bovine mammary epithelial cells involves reduced proteolytic activation of the transcription factor SREBP-1. 1546 41

Milk fat was investigated in lactating dairy cows fed diets supplemented with Ca salts of trans fatty acids (Ca-tFA) or Ca salts of conjugated linoleic acids (Ca-CLA). Forty-five Holstein cows (115 days in milk) were fed a control diet (51% forage; dry matter basis) supplemented with 400 g of EnerG II (Ca salts of palm oil fatty acids) for 2 wk; subsequently, 5 groups of 9 cows each were assigned for 4 wk to the control diet or diets containing 100 g of Ca-CLA or 100, 200, or 400 g of Ca-tFA in a randomized block design. Treatments had no effect on dry matter intake, milk production, protein, lactose, or somatic cell count. Milk fat percentage was reduced from 3.39% in controls to 3.30, 3.04, and 2.98%, respectively, by the Ca-tFA diets and to 2.54% by the Ca-CLA diet. Milk fat yield (1.24 kg/d in controls) was decreased by 60, 130, and 190 g/d with increasing dose of Ca-tFA and by 290 g/d with the Ca-CLA supplement. Consistent with increased endogenous synthesis of cis-9-containing CLA from precursors provided by the Ca-tFA diets, total CLA were similar in milk of cows fed Ca-CLA or Ca-tFA. Compared with controls, the Ca-CLA diet increased trans-10, cis-12-18:2 yield in milk, without altering levels of trans-18:1 isomers. In contrast, yields of most trans-18:1 isomers were elevated in milk of cows fed Ca-tFA diets, whereas yields of trans-10, cis-12-18:2 remained similar to control values. We conclude that milk fat depression can occur without an increase in trans-10, cis-12-18:2 in milk and that other components, perhaps the trans-10-18:1 isomer, may be involved.
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PMID:Changes in milk fat in response to dietary supplementation with calcium salts of trans-18:1 or conjugated linoleic fatty acids in lactating dairy cows. 1548 68

Heat-stressed dairy cattle are bioenergetically similar to early-lactation cows in that dietary energy may be inadequate to support maximum milk and milk component synthesis. Study objectives were to evaluate whether conjugated linoleic acids- (CLA-) induced milk fat depression (MFD) during heat stress would allow for increased milk and milk component synthesis. In addition, CLA effects on production variables and its ability to induce MFD were compared between Holstein and Brown Swiss cows. Multiparous cows (n = 8, Holstein; n = 5, Brown Swiss) averaging 97 +/- 17 d in milk were used in a crossover design during the summer (mean temperature-humidity index = 75.7). Treatment periods were 21 d with a 7-d adaptation period before and between periods. During adaptation periods, all cows received a supplement of palm fatty acid distillate (242 g/d). Dietary treatment consisted of 250 g/d of CLA supplement (78.9 g/d of CLA) or 242 g/d of palm fatty acid distillate to provide equal amounts of fatty acids. The CLA supplement contained a variety of CLA isomers (3.0% trans-8, cis-10; 3.4% cis-9, trans-11; 4.5% trans-10, cis-12; and 4.8% cis-11, trans-13 CLA). Treatments were applied 2 x/d with half of the supplement top-dressed at 0600 h and the remainder top-dressed at 1800 h. There was no overall treatment effect on dry matter intake (23.9 kg/d), milk yield (40.0 kg/d), somatic cell count (305,000), protein (2.86%), or lactose content (4.51%) or yields of these milk components. Supplementation with CLA decreased overall milk fat content and yield by 26 and 30%, irrespective of breed. The reduction of milk fat content and yield was greatest on d 21 (28 and 37%, respectively). Energy availability predicted by energy balance was improved with CLA supplementation compared with controls (3.7 vs. 7.1 Mcal/d, respectively). Respiration rate (78 breaths/min) and skin temperature (35.4 degrees C) during maximum heat load were not affected by treatment. The group receiving CLA had higher total milk fat CLA concentration (9.3 vs. 4.9 mg/g). Supplementation with CLA induced MFD and altered milk fat composition similarly between breeds and improved calculated energy balance during heat stress, but had no effect on production measures under these conditions.
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PMID:Effect of supplemental conjugated linoleic acids on heat-stressed brown swiss and holstein cows. 1582 65

The influence of grass-only diets either from rye-grass-dominated lowland pastures (400 m above sea level) or botanically diverse alpine pastures (2000 m) on the FA profile of milk was investigated using three groups of six Brown Swiss cows each. Two groups were fed grass-only on pasture (P) or freshly harvested in barn (B), both for two experimental periods in the lowlands and, consecutively, two periods on the alp. Group C served as the control, receiving a silage-concentrate diet and permanently staying in the lowlands. Effects of vegetation stage or pasture vs. barn feeding on milk fat composition were negligible. Compared with the control, alpha-linolenic acid (18:3n-3) consumption was elevated in groups P and B (79%; P< 0.001) during the lowland periods but decreased on the alp to the level of C owing to feed intake depression and lower 18:3n-3 concentration in the alpine forage. Average 18:3n-3 contents of milk fat were higher in groups P and B than in C by 33% (P< 0.01) at low and by 96% (P < 0.001) at high altitude, indicating that 18:3n-3 levels in milk were to some extent independent of 18:3n-3 consumption. The cis-9, trans-11 CLA content in milk of grass-fed cows was higher compared with C but lower for the alpine vs. lowland periods whereas the trans-11, cis-13 isomer further increased with altitude. Long-chain n-3 FA and phytanic acid increased while arachidonic acid decreased with grass-only feeding, but none of them responded to altitude. Grass-only feeding increased milk alpha-tocopherol concentration by 86 and 134% at low and high altitude (P < 0.001), respectively. Changes in the ruminal ecosystem due to energy shortage or specific secondary plant metabolites are discussed as possible causes for the high 18:3n-3 concentrations in alpine milk.
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PMID:A study on the causes for the elevated n-3 fatty acids in cows' milk of alpine origin. 1588 68


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