New orthoquinones from the roots of Salvia lanigera

A chloroform extract of the roots of the Egyptian Salvia lanigera Poir. afforded two new orthoquinones, lanigerone (8-hydroxy-3-isopropyl-7-methyl-1,2-naphthoquinone) and salvigerone (methyl 1,10-seco-5(10),6,8,13-abietatetraene-11,12-dion-1-oate) together with two known diterpenoids, arucadiol and pisiferal. Structural assignments of the new compounds were based on spectroscopic methods (UV, IR, MS, ID- and 2D-NMR).     

Optimisation of the biology of soft tissue repair

As identified in this review, over the past twenty years there have been a number of very exciting new developments in the quest to optimise soft tissue repair. Comparing fetal soft tissue injuries, which heal by regeneration, to the adult processes of healing by inflammation-induced scar formation has led to a number of insights into how the latter may be improved. Seeding wounds with embryonic stem cells, bridging gaps with cell-derived "engineered tissues", addition of exogenous hyaluronic acid and modification of wounds to either enhance the growth factors which have been implicated in regeneration (e.g. TGF-B3) or block those implicated in scar formation (eg. TGF-B1) have all shown promise. Our group has quantified numerous cellular, molecular, biomechanical and matrix abnormalities of scar in a rabbit model of ligament healing. Based on these studies which we review here, three matrix deficiencies have been identified which appear to have specific implications to scar weakness: organisational "flaws", abnormal hydroxypyridinoline collagen cross-link densities and abnormally small, slow-maturing collagen fibrils. In tests aimed at finding therapeutic solutions in this model, the addition of a 7ug bolus of TGF-B1 at day 21 or 2.5ng/day of TGF-B1 being pumped into a wound x 21 days increased the size of ligament scars but did not improve their material strength. It also did not alter any of the above-noted matrix deficiencies. A liposome-mediated anti-sense gene therapy approach aimed at decreasing the expression of the proteoglycan decorin in 21-day scars, however, has significantly increased the size of scar collagen fibrils as well as improved these scars mechanically. Based on these positive results from a single dose of only one targeted molecule, we believe that this gene therapy approach has great potential for further scar improvement. If combined with some of the other biological strategies reviewed above, a repair which is closer to true regenerative healing of ligaments, and all soft tissues, may eventually be achieved.     

Gene therapy for ischemic brain diseases

We discuss possible gene therapies for the treatment of ischemic diseases in the central nervous system (CNS). These therapies aim at the prevention of carotid artery restenosis, stimulation of angiogenesis for ischemic brain, protection of neurons against ischemia, and prevention of vasospasm due to subarachnoid hemorrhage (SAH). Carotid artery restenosis can perhaps be approached by preventing vascular smooth muscle cell proliferation via gene therapy in addition to surgical treatment. Cerebral angiogenesis therapy might be applicable to moyamoya disease. Gene therapies with VEGF and HGF to stimulate angiogenesis have been successful in muscle; however, efficacy in the CNS is unknown. Gene transfection efficiency of viral vectors has been poor in the CNS, and the safety of such vectors is questionable. Therefore, development of gene therapy is for neural protection and prevention of vasospasm due to SAH has been limited. Infusion of HVJ-AVE liposomes into monkey cerebrospinal fluid (CSF) space yielded wide-spread gene transfection. HVJ-AVE liposomes may be a promising vector for use in the human CNS. Few currently available gene therapies appear to be options for clinical treatment of cerebral ischemia despite many experimental designs. In addition to the inherent difficulties of treating the CNS, vectors and methods for introducing vectors into the CNS must be improved.     

Development of ELISPOT assay for thyroid autoantibody-producing cells

A new assay system for detection of thyroid-autoantibody-producing cells was developed. This assay is based on the ELISPOT method with antigen-coated nitrocellulose membranes in 96-well microfilter plates. This was more sensitive than conventional methods such as a radioimmunoassay and a passive agglutination method for detection of thyroid-autoantibody production. The coefficients of inter- and intra-assay variations for antibody-producing cells were less than 6.5%. Thus, this assay system can be used to analyse the thyroid-specific immunological abnormalities as a routine test.     

Myocardial sarcoidosis--pathological studies on 7 autopsy cases with particular reference to histological variations]

The present report consists of seven autopsy cases of myocardial sarcoidosis terminating in death 1 month to 5 years after the onset of symptoms. Histologically, they were classified into the following 4 types: a) diffuse nonspecific granulation, b) specific granuloma with giant cells, c) diffuse fibrosis with giant cells, and d) nonspecific fibrosis. Types a) and b) demonstrate active changes, while c) and d) are sequelae of active inflammation. Morphological changes of sarcoidosis were found not only in myocardium but also in both pericardium and endocardium. Although no final conclusions could be obtained as to whether the giant cells appearing in myocardium were of mesenchymal or myogenic origin, the authors favor the latter concept. Changes compatible to sarcoidosis found in other organs in acute cases were scarce and old. On the contrary, more active and variable changes were encountered in protracted cases. The authors consider giant cell myocarditis to be one type of sarcoidosis occurring in the heart.     

Bisindole alkaloids from Voacanga grandifolia leaves

Journal of Natural Medicines - Two new bisindole alkaloids, 12′-O-demethyl-vobtusine-5-lactam and isovobtusine-N-oxide (1 and 2), were isolated from the leaves of Voacanga grandifolia,...     

Expression of SPARC by activated hepatic stellate cells and its correlation with the stages of fibrogenesis in human chronic hepatitis

Secreted protein, acidic and rich in cysteine (SPARC), which functions in tissue remodeling, has been reported to be expressed by myofibroblasts in liver cirrhosis and hepatocellular carcinoma. This study aimed to reveal its expression in chronic hepatitis. Immuno-light and electron microscopy demonstrated that SPARC was expressed by nerve fibers and hepatic stellate cells (HSCs) in the liver parenchyma and myofibroblasts in the fibrous septa. Reaction products were localized in the rough endoplasmic reticulum and nuclear envelope. Serial section analysis demonstrated that SPARC, platelet-derived growth factor receptor-beta, and alpha-smooth muscle actin were co-expressed by HSCs. Quantitative analysis demonstrated that, while SPARC-positive HSCs were sparse in control livers, they significantly increased in number in the livers with chronic hepatitis. There were, however, no significant differences in number among the grades of activity, the stages of fibrosis, or etiology (virus-infected or autoimmune, hepatitis B virus or hepatitis C virus). In liver cirrhosis, however, they significantly decreased in number. The present results indicate that SPARC is expressed by activated HSCs in chronic hepatitis, suggesting the involvement of SPARC in hepatic fibrogenesis after chronic injuries.     

Water may cure patients with Meniere disease

OBJECTIVES/HYPOTHESIS: We examined whether sufficient water intake is effective in the long-term control of vertigo and hearing activity in patients with Meniere disease (MD) for whom conventional therapy has proven unsuccessful. STUDY DESIGN: The authors conducted a time-series study with historical control. METHODS: Eighteen patients with MD in group 1 drank 35 mL/kg per day of water for 2 years. Twenty-nine patients with MD treated with the conventional dietary and diuretic therapy for more than 2 years during 1992 to 1999 at the same hospital were enrolled in a historical control of group 2. RESULTS: Patients in group 1 dramatically relieved vertigo and significantly improved in the hearing of the worst pure-tone average of three frequencies (0.125, 0.25, and 0.5 kHz) (low PTA) during the last 6 months of the study period. In contrast, patients in group 2 became worse in both the four- (0.5, 1, 2, and 4 kHz) frequency PTA and the low PTA, although their vertigo did improve. The number of patients whose hearing were improved, unchanged, and worse were 4, 12, and 2 in group 1 and 2, 11, and 16 in group 2, respectively. CONCLUSION: Deliberate modulation of the intake of water may be the simplest and most cost-effective medical treatment for patients with MD. Larger studies will be needed to confirm these results in a larger patient cohort.