Concentrations of retinol and tocopherols in the milk of cows supplemented with conjugated linoleic acid.

This study was performed to investigate the hypothesis that supplementation of conjugated linoleic acid (CLA) changes the concentrations of retinol and tocopherols in the milk of cows. To investigate this hypothesis, Holstein cows received daily from 3 weeks ante-partum to 14 weeks post-partum either 172 g of a CLA-free rumen-protected control fat (control group, n = 20) or the same amount of a rumen-protected CLA fat, supplying 4.3 g of cis-9, trans-11 CLA and 3.8 g of trans-10, cis-12 CLA per d (CLA group, n = 20). Milk samples (collected at weeks 1, 3, 5, 8 and 11 of lactation) were analysed for retinol, α- and γ-tocopherol concentrations. Milk of cows supplemented with CLA had higher concentrations of retinol (+34%), α-tocopherol (+44%) and γ-tocopherol (+21%) than milk of control cows (p < 0.05). The daily output of these vitamins via milk was also greater in cows of the CLA group than in cows of the control group (+36, 50 and 24% for retinol, α-tocopherol and γ-tocopherol, respectively, p < 0.05). In agreement with higher concentrations of tocopherols, concentrations of thiobarbituric acid-reactive substances, determined in milk of week 5, were lower in cows of the CLA group than in control cows, indicative of a lower susceptibility of milk lipids to peroxidation. Plasma concentrations of retinol and α-tocopherol, determined at 1 and 5 weeks post-partum, were not different between the two groups of cows. In conclusion, this study shows that supplementing dairy cows with a moderate amount of CLA causes an increase of the concentrations of vitamins A and E in the milk and results in an increased output of those vitamins via milk. These effects might be beneficial with respect to the nutritional value of dairy products and the susceptibility of milk fat to oxidative deterioration.

Expression of fibroblast growth factor 21 in the liver of dairy cows in the transition period and during lactation.

Fibroblast growth factor 21 (FGF21) has been identified as a novel hormonal factor involved in the regulation of metabolic adaptations during energy deprivation. The present study aimed to investigate the expression of the FGF21 gene in the liver of dairy cows during the transition from pregnancy to lactation. Therefore, the relative mRNA abundance of FGF21 in liver biopsy samples of 20 dairy cows in late pregnancy (3 weeks pre-partum) and early lactation (1, 5, 14 weeks post-partum) was determined. It was observed that hepatic mRNA abundance of FGF21 at 1 week post-partum was dramatically increased (110-fold) compared to 3 weeks pre-partum (p < 0.001). With progress of lactation, mRNA concentration of FGF21 was declining; nevertheless, mRNA abundance at 5 and 14 weeks post-partum remained 25- and 10-fold increased compared to 3 weeks pre-partum (p < 0.001). Using a gene array technique, it was found that many genes involved in fatty acid oxidation, gluconeogenesis and ketogenesis were up-regulated during early lactation compared to late pregnancy. Moreover, there were positive linear correlations between hepatic mRNA concentration of FGF21 and mRNA concentrations of genes involved in ketogenesis as well as carnitine synthesis and carnitine uptake at various time-points during lactation, indicating that FGF21 could play a role in ketogenesis and carnitine metabolism in the liver of dairy cows (p < 0.05). In overall, the present study shows that expression of the FGF21 gene is strongly up-regulated during the transition period. It is assumed that the up-regulation of FGF21 might play an important role in the adaptation of liver metabolism during early lactation in dairy cows such as in other species.

Expression of target genes of nuclear factor E2-related factor 2 in the liver of dairy cows in the transition period and at different stages of lactation.

In the liver of dairy cows, the production of cytokines is enhanced during the periparturient phase, which in turn leads to inflammation and an impairment of hepatic function. Nuclear factor E2-related factor 2 (Nrf2) is a redox-sensitive transcription factor that controls the transcription of genes encoding various antioxidative and cytoprotective proteins. In the present study, we investigated the hypothesis that Nrf2 is activated in the liver of dairy cows during the periparturient phase to protect the liver against the deleterious effects of cytokines and reactive oxygen species. Therefore, we determined relative mRNA abundances of TNF (encoding tumor necrosis factor-α), various acute phase proteins and several Nrf2 target genes in liver biopsy samples of 20 dairy cows at each time point from 3 wk antepartum to 1, 5, and 14 wk postpartum. We observed an increase in mRNA abundances of TNF and acute-phase proteins [serum amyloid A 3 (SAA3), haptoglobin (HP), and C-reactive protein (CRP)] from 3 wk antepartum to 1 wk postpartum, indicative of a proinflammatory condition. Messenger RNA abundances of various Nrf2 target genes with antioxidative or cytoprotective functions [glutathione peroxidase 3 (GPX3); microsomal glutathione S-transferase 3 (MGST3); superoxide dismutase (SOD1); catalase (CAT); metallothioneins 1A, 1E, and 2A (MT1A, MT1E, and MT2A, respectively); NAD(P)H dehydrogenase, quinone 1 (NQO1); heme oxygenase 2 (HMOX2); and UDP glucuronosyltransferase 1 family, polypeptide A1 (UGT1A1)] were also greatly increased from 3 wk antepartum to 1 wk postpartum. From 1 wk postpartum to later lactation, mRNA abundances of all the Nrf2-target genes considered declined but remained at levels that were higher than those in 3 wk antepartum. No correlations were found, however, between plasma concentrations of nonesterified fatty acids or ß-hydroxybutyrate and mRNA abundances of Nrf2 target genes, indicating that a negative energy balance might not have been the main factor responsible for upregulation of those genes in the liver during early lactation. In conclusion, this study provides additional evidence that the periparturient phase in dairy cows is associated with a proinflammatory condition in the liver. Moreover, it is shown for the first time that the transition from pregnancy to lactation leads to a strong upregulation of Nrf2 target genes with antioxidative or cytoprotective properties, which might be another physiologic means to prevent the liver against damage by the inflammation process and an increased generation of reactive oxygen species.

Changes in the expression of hepatic genes involved in cholesterol homeostasis in dairy cows in the transition period and at different stages of lactation.

This study was performed to investigate changes in expression level of genes involved in hepatic cholesterol metabolism in the transition from pregnancy to lactation and during different stages of lactation in dairy cows. Therefore, relative mRNA abundances of several genes involved in various pathways of cholesterol homeostasis in liver biopsy samples of 20 dairy cows, taken in late pregnancy (3 wk prepartum) and early lactation (1, 5, and 14 wk postpartum), were determined. At 1 wk postpartum, hepatic mRNA abundances of genes involved in cholesterol synthesis (3-hydroxy-3-methylglutaryl-coenzyme A reductase, mevalonate kinase, and farnesyl diphosphate synthase), cholesterol uptake from blood (low-density lipoprotein receptor), bile acid synthesis (cholesterol-7α-hydroxylase), cholesterol efflux [ATP-binding cassette (ABC) transporter A1 and ABCG1], esterification of cholesterol (acyl-coenzyme A:cholesterol acyltransferase), and proteins involved in assembly and secretion of very low-density lipoproteins (microsomal triglyceride transfer protein, ApoB100) were increased compared with 3 wk prepartum. The mRNA abundances of most of these genes decreased after 1 wk of lactation and reached levels in 5 and 14 wk of lactation similar to those at 3 wk prepartum. Only mRNA abundances of cholesterol-7α-hydroxylase, ABC transporters, and ApoB100 remained at 5 and 14 wk postpartum at levels higher than those at 3 wk prepartum. Hepatic cholesterol abundance was highest at 1 wk postpartum and was, thereafter, decreasing to values similar to that at 3 wk prepartum. Overall, this study shows that the onset of lactation is associated with an increased expression of various genes involved in cholesterol metabolism in the liver of dairy cows, suggesting that pronounced changes in hepatic cholesterol metabolism take place in the periparturient phase.

Effects of a rumen-protected mixture of conjugated linoleic acids on hepatic expression of genes involved in lipid metabolism in dairy cows.

Supplementation of conjugated linoleic acids (CLA) reduces milk fat content in dairy cows and, thus, may be a useful dietary strategy to improve energy balance during early lactation. The present study was performed to investigate whether supplementation of CLA could have adverse effects on hepatic lipid metabolism such as observed in rodents. For this aim, 40 Holstein cows were allotted to 2 groups, which were fed daily 172 g of either a CLA-free, rumen-protected control fat (control group) or a rumen-protected CLA fat supplying 4.3g of cis-9,trans-11 CLA and 3.8 g of trans-10,cis-12 CLA per day (CLA group). To identify potential changes of lipid metabolism, expression of several genes involved in lipid metabolism was determined in liver biopsy samples taken at wk 5 of lactation, using a whole-genome gene chip. In the CLA group, milk fat content and daily milk fat yield were lower than in the control group. Milk yield was higher, whereas fat-corrected milk and energy-corrected milk were lower in the CLA group than in the control group. The CLA group, moreover, had an improved energy balance. To study potential effects of CLA on hepatic lipid metabolism, we considered 6 genes encoding fatty acid transporters, 7 genes involved in intracellular fatty acid transport, 21 and 7 genes, respectively, involved in mitochondrial and peroxisomal ß-oxidation, 6 genes of carnitine metabolism, 3 genes of ketogenesis, 21 genes involved in fatty acid and triacylglycerol synthesis, 17 genes involved in cholesterol metabolism, and 20 genes involved in lipoprotein metabolism. None of these genes was differentially regulated between the CLA group and the control group. Gene chip data were confirmed by quantitative PCR analysis, which revealed no difference in the expression of key enzymes of various pathways such as lipogenesis, ß-oxidation, and ketogenesis between the 2 groups of cows. In line with those findings, concentrations of triacylglycerols and cholesterol in liver and plasma were not different between the 2 groups of cows. In conclusion, the present study shows that CLA supplementation at a dose effective for milk fat depression does not induce adverse effects on hepatic lipid metabolism in dairy cows.

Influence of a rumen-protected conjugated linoleic acid mixture on carcass traits and meat quality in young Simmental heifers.

The aim of the present study was to investigate the influence of feeding rumen-protected CLA during the early growing period on physical and chemical beef properties in young Simmental heifers. A total of 36 heifers (5 mo old; initial BW 185 ± 21 kg) were fed 250 g of different rumen-protected fats daily for 16 wk in 1 of 3 treatment groups: 250 g of a CLA-free control fat; 100 g of a CLA fat containing 2.4% of cis-9,trans-11 CLA and 2.1% of trans-10,cis-12 CLA and 150 g control fat; or 250 g of the CLA fat. Heifer growth performance variables as well as carcass weight, classification (conformation and fatness), and weights of organs and fat depots were not affected (P > 0.05) by CLA supplementation. Concentration of trans-10,cis-12 CLA in tissues (LM and subcutaneous fat) was dose-dependently increased (P < 0.01) by CLA supplementation, whereas that of cis-9,trans-11 CLA in these tissues did not differ (P > 0.05) between groups. The ratio of SFA to MUFA was increased (P < 0.01) in tissues of CLA-fed heifers compared with control heifers. Concentration of α-tocopherol in LM was greater (P = 0.01) in heifers of the 2 CLA groups than in control heifers. Other quality characteristics such as drip loss during storage, cooking loss, intramuscular fat content, and color variables in LM did not differ (P > 0.05) between groups. In conclusion, the present study demonstrates that feeding rumen-protected CLA during the early growing period changes tissue fatty acid composition but does not influence beef quality variables. Performance variables and carcass traits in young heifers, unlike in pigs and laboratory animals, are not influenced by CLA feeding.

Effect of a rumen-protected conjugated linoleic acid mixture on hepatic lipid metabolism in heifers.

This study was performed to assess the effects of rumen-protected conjugated linoleic acid (CLA) on hepatic lipid metabolism in heifers. In particular, it was of interest whether feeding CLA causes development of fatty liver as observed recently in mice. Thirty-six growing heifers with an initial body weight of 185 kg were allotted to three treatment groups and fed daily 250 g of different rumen-protected fats for 16 weeks: The control group received 250 g of a CLA-free control fat, the CLA100 group received 100 g of a CLA fat containing 2.4% of cis-9, trans-11 CLA and 2.1% of trans-10, cis-12 CLA and 150 g control fat and the CLA250 group received 250 g of the CLA fat. CLA supplementation had no effect on animal performance parameters, liver weight and hepatic triglyceride concentration. Moreover, mRNA expression of hepatic genes involved in lipogenesis, ß-oxidation and fatty acid transport was not influenced by dietary CLA. The fatty acid composition of hepatic total lipids, with particular consideration of ratios of fatty acids indicative of Δ9-, Δ6- and Δ5-desaturation, was also less influenced by dietary CLA. In conclusion, the study shows that dietary rumen-protected CLA has less effect on hepatic lipid metabolism in young heifers and does not induce the development of a fatty liver such as in mice.

Supply chain optimization: a practitioner's perspective on the next logistics breakthrough.

The objective of this paper is to profile a practitioner's perspective on supply chain optimization and highlight the critical elements of this potential new logistics breakthrough idea. The introduction will briefly describe the existing distribution network, and business environment. This will include operational statistics, manufacturing software, and hardware configurations. The first segment will cover the critical success factors or foundations elements that are prerequisites for success. The second segment will give you a glimpse of a "working game plan" for successful migration to supply chain optimization. The final segment will briefly profile "bottom-line" benefits to be derived from the use of supply chain optimization as a strategy, tactical tool, and competitive advantage.

Invalidez en el sistema privado de pensiones en Chile / Disability in the private allowances system in Chile

We analyzed 13,456 consecutive cases judged between August 1990 and April 1992. Mortality was registered up to 12 months after judgement. Total incapacity was determined in 4,158 cases (30.9 percent), parcial incapacity in 1,340 (9,9 percent) and minor incapacity in 7,958 (59,1 percent). Osteoarticular diseases were the main cause of disability in 4,460 patients (33,1 percent) and 77,8 percent of patients with malignant tumors were considered as having total incapacity. Mortality was 17 percent among subjects with total incapacity, 1,5 percent among those with partial disability and 1 percent among those with minor disability. The cause of death was related to the main disabling disease in 94 percent of subjects with total incapacity and 66,6 percent of those with partial incapacity. Osteoarticular diseases are the main cause of inability among workers ascribed to a private pension system

Comparison of transcutaneous incisions used for exposure of the infraorbital rim and orbital floor: a retrospective study.

One hundred and five patients were investigated for functional and aesthetic impairments following treatment of orbital trauma through subciliary, mid-lower eyelid, or infraorbital incisions. The progress of impairments with time was assessed, and the merits and shortcomings of each of the three approaches were established. The results showed that impairments persisting up to 6 months postoperatively have virtually not receded even after 6 years. The infraorbital incision showed the highest frequency of impairments, followed by the subciliary incision. The mid-lower eyelid incision showed the best results, with an impairment frequency well below those of the other two approaches. This approach seems to combine the advantages of the infraorbital incision with the unnoticeable scar formation associated with the subciliary incision.

Combined use of carcinoembryonic antigen and tissue polypeptide antigen in oncologic therapy and surveillance.

In the Radiology Clinic of our hospital at present more than 2000 patients have been under surveillance using carcinoembryonic antigen (CEA) and tissue polypeptide antigen (TPA) as markers. The available results have indicated that a combination of both parameters may be applicable in monitoring therapy and in the surveillance thereafter in a variety of cancer sites. It was advantageous to utilize a common index derived from the CEA and TPA serum values after natural logarithmic transformation. Hence, discrimination could be achieved between patients without evidence of disease, and those with progressive disease, eg, in breast cancer with a probability of 95%. The following probabilities were established in 10 other tumor sites: colorectum, 96%; seminoma, 94%; lung, 93%; prostate and bladder, 90%; hypernephroma, 87%; sarcoma, 86%; thyroid, 84%; melanoma, 83%; head and neck, 77%; female genitals, 76%. CEA alone was not applicable in some localized tumors, such as seminoma, melanoma, hypernephroma, and sarcoma. Also, in monitoring patients under chemotherapy, it was established in the follow-up of different cancer sites that TPA was superior to CEA. A concordance with the clinical efficacy of the chemotherapy was found for TPA in 94%, for CEA in 54%, and for both markers in 52%. Thus, as a typical proliferation antigen, TPA appeared to react with a greater sensitivity than CEA on the cytostatic effect of chemotherapy.

[Postoperative radiotherapy of astrocytomas grade 3 and 4 with the radiosensitizer misonidazole. -End results of a multicentric controlled German study]. / Die postoperative Strahlenbehandlung von Astrozytomen Grad 3 und 4 mit dem Strahlensensibilisator Misonidazol. Endergebnis einer multizentrischen und kontrollierten deutschen Studie.

102 patients entered a multicentric randomized study from May 1978 till December 1980. After an operative removal of a supratentorial astrocytoma grade 3 or 4 all patients were treated by radiotherapy of the whole brain with 40 Gy, and after a rest of 1 to 2 weeks with a boost dose of 20 Gy to the tumor region. By randomization the patients got misonidazole (400 mg/m2) to each of the 30 fractions or a placebo. The overall tolerance was good. A mild transient peripheral neuropathy was seen only in 2 patients. The median of survival time was not significantly different for both groups with 16 months (grade 3) and 10 months (grade 4). Thus a radiosensitizing effect of misonidazole was not proven.

[Perioperative behavior of prostaglandin E2 (PGE2) and 13,14-dihydro-15-keto-PGF2 alpha (DHK-PGF2 alpha) in the serum in bronchial cancer]. / Untersuchungen zum perioperativen Verhalten von Prostaglandin E2 (PGE2) und 13,14-dihydro-15-keto-PGF2 alpha (DHK-PGF2 alpha) im Serum beim Bronchialkarzinom.

The perioperative behaviour of PGE2 and DHK-PGF2 alpha was studied in peripheral blood of patients undergoing lung surgery. The measurement of prostaglandins was performed by RIA after an extraction procedure. Common control criteria were observed. In 39 patients blood sampling was performed preoperatively and 2 weeks postoperatively. PGE2 and DHK-PGF2 alpha were significantly elevated in 8 patients with lung cancer before the operation. Postoperatively the concentrations decreased; 2 weeks later, DHK-PGF2 alpha was still slightly increased, PGE2 had normalized. 9 patients suffering from tuberculosis had normal serum concentrations of PGE2 and DHK-PGF2 alpha before and after resection procedures. In 8 cases the resection of benign lung diseases did not cause any abnormal reactions. In 2 special groups blood sampling was performed the following way: in 4 cancer patients and 3 tuberculosis patients blood was collected preoperatively, 5 times in the first hour after lung resection and 1 day and 2 weeks after operation. It could be demonstrated that PGE2 and DHK-PGF2 alpha almost completely normalized within the first postoperative hour in cancer patients, whereas no significant alterations could be found in tuberculosis. After discussion of technical problems in the measurement of prostaglandins the alterations of PG concentrations after lung cancer resection are emphasized.

[Diagnostic value of radionuclide bone imaging in monitoring skeletal metastases (author's transl)]. / Der Informationswert der Knochenszintigraphie für Verlaufskontrollen bei Skeletmetastasen. Am Beispiel des Beckenskelets.

In typical cases with pelvic metastases a close relationship is demonstrated between nuclear medicine and radiologic findings depending on the kind of therapy. For this reason total body radionuclide studies should not only be recommended for screening but also for therapeutic monitoring. Positive radionuclide findings should be supplemented by roentgenologic studies of the areas selected in that way.

[Radioimmunologic determination of immunoglobulin E in neoplasms]. / Radioimmunologische Bestimmung des Immunglobulins E bei Neoplasmen

3000 IgE serum concentrations were determine d radioimmunologically in a large group of 1616 tumor patients and a group of 308 controls. Because of a wide scattering the individual IgE levels do not give a diagnostic indication. On the other hand we have found a highly significant difference (p less than 0.001) between the IgE levels of male and female tumor patient-groups, which does not exist among the controls. Female patients tend to lower, male patients to higher levels. In patients with carcinoma of the testis three times higher IgE levels were found. Their relation to a coincidence with high HCG levels is discussed. Furthermore IgE follow up-studies are described. They correlate close by with the clinical picture. Consequently IgE follow up-studies are applicable to tumor prognosis and possibly to tumor therapy.