[Fetal programming of cardiovascular disease: new causes and underlying mechanisms]

There exists an association between pathologic events occurring during early life and the development of cardiovascular disease in adulthood. For example, transient perinatal hypoxemia predisposes to exaggerated hypoxic pulmonary hypertension and preeclampsia predisposes the offspring to pulmonary and systemic endothelial dysfunction later in life. The latter finding offers a scientific basis for observations demonstrating an increased risk for premature cardiovascular morbidity in this population. Very recently, we showed that offspring of assisted reproductive technologies also display generalized vascular dysfunction and early arteriosclerosis. Studies in animal models have provided evidence that oxidative stress and/or epigenetic alterations play an important pathophysiological role in the fetal programming of cardiovascular disease.

Xanthohumol ameliorates atherosclerotic plaque formation, hypercholesterolemia, and hepatic steatosis in ApoE-deficient mice

SCOPE: Xanthohumol (XN), a prenylated antioxidative and anti-inflammatory chalcone from hops, exhibits positive effects on lipid and glucose metabolism. Based on its favorable biological properties, we investigated whether XN attenuates atherosclerosis in western-type diet-fed apolipoprotein-E-deficient (ApoE(-/-) ) mice. METHODS AND RESULTS: XN supplementation markedly reduced plasma cholesterol concentrations, decreased atherosclerotic lesion area, and attenuated plasma concentrations of the proinflammatory cytokine monocyte chemoattractant protein 1. Decreased hepatic triglyceride and cholesterol content, activation of AMP-activated protein kinase, phosphorylation and inactivation of acetyl-CoA carboxylase, and reduced expression levels of mature sterol regulatory element-binding protein (SREBP)-2 and SREBP-1c mRNA indicate reduced lipogenesis in the liver of XN-fed ApoE(-/-) mice. Concomitant induction of hepatic mRNA expression of carnitine palmitoyltransferase-1a in ApoE(-/-) mice-administered XN suggests increased fatty acid beta-oxidation. Fecal cholesterol concentrations were also markedly increased in XN-fed ApoE(-/-) mice compared with mice fed western-type diet alone. CONCLUSION: The atheroprotective effects of XN might be attributed to combined beneficial effects on plasma cholesterol and monocyte chemoattractant protein 1 concentrations and hepatic lipid metabolism via activation of AMP-activated protein kinase.

Willy Loman and the "Soul of a New Machine": Technology and the Common Man

As Death of a Salesman opens, Willy Loman returns home “tired to the death” (p. 13). Lost in reveries about the beautiful countryside and the past, he's been driving off the road; and now he wants a cheese sandwich. But Linda's suggestion that he try a new American-type cheese — “It's whipped” (p. 16) — irritates Willy: “Why do you get American when I like Swiss?” (p. 17). His anger at being contradicted unleashes an indictment of modern industrialized America: The street is lined with cars. There's not a breath of fresh air in the neighborhood. The grass don't grow any more, you can't raise a carrot in the back yard. (p. 17). In the old days, “This time of year it was lilac and wisteria.” Now: “Smell the stink from that apartment house! And another one on the other side…” (pp. 17–18). But just as Willy defines the conflict between nature and industry, he pauses and simply wonders: “How can they whip cheese?” (p. 18). The clash between the old agrarian ideal and capitalistic enterprise is well documented in the literature on Death of a Salesman, as is the spiritual shift from Thomas Jefferson to Andrew Carnegie to Dale Carnegie that the play reflects. The son of a pioneer inventor and the slave to broken machines, Willy Loman seems to epitomize the victim of modern technology.

Matrix metalloproteinase inhibition lowers mortality and brain injury in experimental pneumococcal meningitis

Pneumococcal meningitis (PM) results in high mortality rates and long-lasting neurological deficits. Hippocampal apoptosis and cortical necrosis are histopathological correlates of neurofunctional sequelae in rodent models and are frequently observed in autopsy studies of patients who die of PM. In experimental PM, inhibition of matrix metalloproteinases (MMPs) and/or tumor necrosis factor (TNF)-converting enzyme (TACE) has been shown to reduce brain injury and the associated impairment of neurocognitive function. However, none of the compounds evaluated in these studies entered clinical development. Here, we evaluated two second-generation MMP and TACE inhibitors with higher selectivity and improved oral availability. Ro 32-3555 (Trocade, cipemastat) preferentially inhibits collagenases (MMP-1, -8, and -13) and gelatinase B (MMP-9), while Ro 32-7315 is an efficient inhibitor of TACE. PM was induced in infant rats by the intracisternal injection of live Streptococcus pneumoniae. Ro 32-3555 and Ro 32-7315 were injected intraperitoneally, starting at 3 h postinfection. Antibiotic (ceftriaxone) therapy was initiated at 18 h postinfection, and clinical parameters (weight, clinical score, mortality rate) were recorded. Myeloperoxidase activities, concentrations of cytokines and chemokines, concentrations of MMP-2 and MMP-9, and collagen concentrations were measured in the cerebrospinal fluid. Animals were sacrificed at 42 h postinfection, and their brains were assessed by histomorphometry for hippocampal apoptosis and cortical necrosis. Both compounds, while exhibiting disparate MMP and TACE inhibitory profiles, decreased hippocampal apoptosis and cortical injury. Ro 32-3555 reduced mortality rates and cerebrospinal fluid TNF, interleukin-1β (IL-1β) and collagen levels, while Ro 32-7315 reduced weight loss and cerebrospinal fluid TNF and IL-6 levels.

Halakhot shevuʿot ha-Yehudim : kurtze Information, was einem Juden, der einen Eyd schwören solle, vorzuhalten, und wie er selbigen zu praestiren, zur Nachricht ertheilt

von Philipp Ernst Christfelß

Prophylaxis of infectious complications with colony-stimulating factors in adult cancer patients undergoing chemotherapy-evidence-based guidelines from the Infectious Diseases Working Party AGIHO of the German Society for Haematology and Medical Oncology (DGHO).

BACKGROUND Current evidence on myelopoietic growth factors is difficult to overview for the practicing haematologist/oncologist. International guidelines are sometimes conflicting, exclude certain patient groups, or cannot directly be applied to the German health system. This guideline by the Infectious Diseases Working Party (AGIHO) of the German Society of Haematology and Medical Oncology (DGHO) gives evidence-based recommendations for the use of G-CSF, pegylated G-CSF, and biosimilars to prevent infectious complications in cancer patients undergoing chemotherapy, including those with haematological malignancies. METHODS We systematically searched and evaluated current evidence. An expert panel discussed the results and recommendations. We then compared our recommendations to current international guidelines. RESULTS We summarised the data from eligible studies in evidence tables, developed recommendations for different entities and risk groups. CONCLUSION Comprehensive literature search and expert panel consensus confirmed many key recommendations given by international guidelines. Evidence for growth factors during acute myeloid leukaemia induction chemotherapy and pegfilgrastim use in haematological malignancies was rated lower compared with other guidelines.

Henr. Bened. Starki Lux Ebraea ex nouissimis Principiis cum perpetuis Notis Criticis atque Rationibus Accensa

Erscheinungsjahr lt. "Katalog der Judaica und Hebraica, Frankfurt am Main, 1932". - Teilw. in hebr. Schr.

Sēfer yedîʿat ʿôlām : un dizuś bšraibung iz niṭ oiz gṭrachṭ als ein isṭorje zonder alein iz oiz gšribn ... un haṭ ein sifrei metik gwezin fun l ošn ʿarābî oif lošn hakoideš ... un fun lošn hakoideš oif ṭaiṭš gešṭelṭ ...

Digitalisat der Ausg. [S.l.], 1718/19

Sēder qînôt miṭ ṭaiṭš : ke-minhag q"q aškenazzîm weil ich hob gizehn doś di (qines) di mir an (Tišaʿ be-Av) ṭun zogn zain ... šwer tzu fur šṭin ...

Digitalisat der Ausg. Amśṭrdm, [1717/18]