Evaluation of hyperforin analogues for inhibition of 5-lipoxygenase

The acylphloroglucinol hyperforin, a constituent of the herb Hypericum perforatum (St. John's wort), was recently identified as potent and direct inhibitor of 5-lipoxygenase (5-LO), the key enzyme in the biosynthesis of proinflammatory leukotrienes. In this study, naturally occurring analogues of hyperforin, isolated from H. perforatum, as well as a series of synthetic derivatives obtained by chemical modification of hyperforin by acylation, alkylation or oxidation, were analysed for the inhibition of 5-LO. The efficacies of these compounds were evaluated in intact human polymorphonuclear leukocytes, but also the inhibitory effects on isolated recombinant human 5-LO were investigated. Our data show that some of the oxidised hyperforin derivatives possess even improved efficacy, whereas alkylation and acylation have detrimental effects.     

Neural connections between the hypothalamus and the liver

After receiving information from afferent nerves, the hypothalamus sends signals to peripheral organs, including the liver, to keep homeostasis. There are two ways for the hypothalamus to signal to the peripheral organs: by stimulating the autonomic nerves and by releasing hormones from the pituitary gland. In order to reveal the involvement of the autonomic nervous system in liver function, we focus in this study on autonomic nerves and neuroendocrine connections between the hypothalamus and the liver. The hypothalamus consists of three major areas: lateral, medial, and periventricular. Each area has some nuclei. There are two important nuclei and one area in the hypothalamus that send out the neural autonomic information to the peripheral organs: the ventromedial hypothalamic nucleus (VMH) in the medial area, the lateral hypothalamic area (LHA), and the periventricular hypothalamic nucleus (PVN) in the periventricular area. VMH sends sympathetic signals to the liver via the celiac ganglia, the LHA sends parasympathetic signals to the liver via the vagal nerve, and the PVN integrates information from other areas of the hypothalamus and sends both autonomic signals to the liver. As for the afferent nerves, there are two pathways: a vagal afferent and a dorsal afferent nerve pathway. Vagal afferent nerves are thought to play a role as sensors in the peripheral organs and to send signals to the brain, including the hypothalamus, via nodosa ganglia of the vagal nerve. On the other hand, dorsal afferent nerves are primary sensory nerves that send signals to the brain via lower thoracic dorsal root ganglia. In the liver, many nerves contain classical neurotransmitters (noradrenaline and acetylcholine) and neuropeptides (substance P, calcitonin gene-related peptide, neuropeptide Y, vasoactive intestinal polypeptide, somatostatin, glucagon, glucagon-like peptide, neurotensin, serotonin, and galanin). Their distribution in the liver is species-dependent. Some of these nerves are thought to be involved in the regulation of hepatic function as well as of hemodynamics. In addition to direct neural connections, the hypothalamus can affect metabolic functions by neuroendocrine connections: the hypothalamus-pancreas axis, the hypothalamus-adrenal axis, and the hypothalamus-pituitary axis. In the hypothalamus-pancreas axis, autonomic nerves release glucagon and insulin, which directly enter the liver and affect liver metabolism. In the hypothalamus-adrenal axis, autonomic nerves release catecholamines such as adrenaline and noradrenaline from the adrenal medulla, which also affects liver metabolism. In the hypothalamus-pituitary axis, release of glucocorticoids and thyroid hormones is stimulated by pituitary hormones. Both groups of hormones modulate hepatic metabolism. Taken together, the hypothalamus controls liver functions by neural and neuroendocrine connections.     

Characterization of Aeromonas caviae antigens which cross-react with Shigella boydii 5.

Live and boiled cells of 16 strains of Aeromonas caviae, isolated from patients with diarrhea, agglutinated with Shigella boydii 5 antiserum in a slide test. Further studies with seven selected strains showed agglutination with boiled cells in a tube test. Lipopolysaccharide antigen extracted from one of these strains cross-reacted with S. boydii 5 in enzyme-linked immunosorbent assay and immunoblot studies. Either all or the majority of the seven strains possessed properties deemed to be diarrheagenic.     

Metachronous and multiple aneurysmal bone cysts: a rare variant of primary aneurysmal bone cysts

In 1942, Jaffe and Lichtenstein introduced the term aneurysmal bone cyst (ABC). Primary ABC is characterized by the presence of spongy or multi-cameral cystic tissue filled with blood. The process is benign, but it is locally destructive and has a high propensity for recurrence. In this paper, we present the third case of multiple metachronous primary ABCs as a rare variant of ABC. We describe the 10-year history of a 12-year-old boy with metachronous multiple primary ABCs at five different sites (right proximal humerus, right ulna, bilateral distal radius and right lateral clavicle). Furthermore, our patient suffered from vascular malformations, such as aortic isthmus stenosis, hypoplastic thoraco-abdominal aorta and bilateral renal artery stenosis. To date, in contrast to solitary ABC, the multiple lesions have been found more frequently in male individuals. Using interphase cytogenetics, we analyzed three of five of the patients ABCs and one of these was also analyzed by GTG-banding. No chromosomal abnormalities were found. Significantly, we excluded the missense mutation of codon 201 in guanine nucleotide-binding protein 1 gene consistently found in McCune-Albright syndrome (MAS) and in non-MAS cases of polyostotic fibrous dysplasia of bone with or without secondary ABC.     

Schistosomiasis: an unusual cause of tubal infertility

A case report of a Nigerian woman having an unusual cause oftubal infertility is presented. On histological examinationof the Fallopian tube, ova of Schistosoma haematobium enclosingliving miracidia were found in the smooth muscle layer of theFallopian tube and its mesosalpinx. Mechanisms of tubal involvementare analysed. The case indicates the need to consider schisto-somiasisas a possible aetiological factor in patients with tubal infertilitycoming from areas where the disease is endemic.     

Adapting industry-style business model to academia in a system of Performance-based Incentive Compensation.

Performance-Based Incentive Compensation (PBIC) plans currently prevail throughout industry and have repeatedly demonstrated effectiveness as powerful motivational tools for attracting and retaining top talent, enhancing key indicators, increasing employee productivity, and, ultimately, enhancing mission-based parameters. The University of Arkansas for Medical Sciences (UAMS) College of Medicine introduced its PBIC plan to further the transition of the college to a high-performing academic and clinical enterprise. A forward-thinking compensation plan was progressively implemented during a three-year period.After the introduction of an aggressive five-year vision plan in 2002, the college introduced a PBIC plan designed to ensure the retention and recruitment of high-quality faculty through the use of uncapped salaries that reflect each faculty member's clinical, research, and education duties. The PBIC plan was introduced with broad, schoolwide principles adaptable to each department and purposely flexible to allow for tailor-made algorithms to fit the specific approaches required by individual departments.As of July 2006, the college had begun to reap a variety of short-term benefits from Phase I of its PBIC program, including increases in revenue and faculty salaries, and increased faculty morale and satisfaction.Successful implementation of a PBIC plan depends on a host of factors, including the development of a process for evaluating performance that is considered fair and reliable to the entire faculty. The college has become more efficient and effective by adopting such a program, which has helped it to increase overall productivity. The PBIC program continues to challenge our faculty members to attain their highest potential while rewarding them accordingly.     

Reproducibility of Immunological Tests Used To Assess Multiple Chemical Sensitivity Syndrome

Whether persons with multiple chemical sensitivity syndrome (MCS) have immunological abnormalities is unknown. To assess the reliability of selected immunological tests that have been hypothesized to be associated with MCS, replicate blood samples from 19 healthy volunteers, 15 persons diagnosed with MCS, and 11 persons diagnosed with autoimmune disease were analyzed in five laboratories for expression of four T-cell surface activation markers (CD25, CD26, CD38, and HLA-DR) and in four laboratories for autoantibodies (to smooth muscle, thyroid antigens, and myelin). For T-cell activation markers, the intralaboratory reproducibility was very good, with 90% of the replicates analyzed in the same laboratory differing by ≤3%. Interlaboratory differences were statistically significant for all T-cell subsets except CD4⁺ cells, ranging from minor to eightfold for CD25⁺ subsets. Within laboratories, the date of analysis was significantly associated with the values for all cellular activation markers. Although reproducibility of autoantibodies could not be precisely assessed due to the rarity of abnormal results, there were inconsistencies across laboratories. The effect of shipping on all measurements, while sometimes statistically significant, was very small. These results support the reliability of fresh and shipped samples for detecting large (but perhaps not small) differences between groups of donors in the T-cell subsets tested. When comparing markers that are not well standardized, it may be important to distribute samples from different study groups evenly over time.     

Züchtung des Variolavirus in der infantilen Maus

Zusammenfassung Das Variolavirus konnte aus menschlichem Pustel- und Krustenmaterial intraperitoneal in infantilen Mäusen angezüchtet und in fortlaufenden Passagen weitergeführt werden. Es blieb innerhalb von 20 Passagen in bezug auf seine biologischen Eigenschaften im Hühnerembryo stabil. Eintägige Mäuse waren empfänglicher als dreitägige Tiere. Innerhalb verschiedener Mäusefamilien bestand eine unterschiedliche Resistenz gegenüber der Variolainfektion. Bei resistenteren Tieren vermehrte sich das Virus, ohne klinische Erscheinungen zu verursachen.Ein besonders bevorzugtes Organ für die Vermehrung des Variolavirus war die Lunge.Bei infizierten, klinisch aber gesunden Mäusen ließ sich aus den Lungen der Tiere in einem Zeitraum von 45 Tagen p. i. infektiöses Variolavirus züchten.     

Mouse macrophage development in the absence of the common γ chain: defining receptor complexes responsible for IL-4 and IL-13 signaling

The common γ chain (γ_c) forms a critical component of the receptors for interleukins (IL)-2, IL-4, IL-7, IL-9, and IL-15. We analyzed γ_c-deficient mice to define a role for γ_c signaling in the development and function of the macrophage lineage. No major differences in absolute cell numbers, cell surface phenotype, or in vitro function of γ^?_c compared to γ⁺_c macrophages were observed. We therefore conclude that signaling through the γ_c chain is not essential for the differentiation of mouse macrophages. Although B and T cells require γ_c for IL-4 responses, IL-4 up-regulated major histocompatibility class II molecules and inhibited nitric oxide production from γ^?_c macrophages following stimulation with lipopolysaccharide and interferon-γ. γ^?_c macrophages could also respond to IL-13, consistent with the model of a type II IL-4 receptor α/IL-13R which can function in the absence of γ_c. Both IL-4 and IL-13 responses could be completely inhibited with the mouse IL-4 antagonist QY, suggesting that all of the observed IL-13 responses pass through the type II receptor, making it the primary signaling receptor complex for IL-13 in mouse macrophages.