Some observations on the effect of Daflon (micronized purified flavonoid fraction of Rutaceae aurantiae) in bancroftian filarial lymphoedema

BACKGROUND: Morbidity management is a core component of the global programme for the elimination of lymphatic filariasis. In a double-blind clinical trial, the tolerability and efficacy of Daflon (500 mg) + DEC (25 mg) or DEC (25 mg) alone, twice daily for 90 days, was studied in 26 patients with bancroftian filarial lymphoedema. RESULTS: None of the patients in either drug group reported any adverse reaction throughout the treatment period (90 days). Haematological and biochemical parameters were within normal limits and there was no significant difference between the pre-treatment (day 0) and post-treatment (day 90) values. The group receiving Daflon showed significant reduction in oedema volume from day 90 (140.6 PlusMinus; 18.8 ml) to day 360 (71.8 PlusMinus; 20.7 ml) compared to the pre-treatment (day 0, 198.4 PlusMinus; 16.5 ml) value. This accounted for a 63.8% reduction in oedema volume by day 360 (considering the pre-treatment (day 0) as 100%). In the DEC group, the changes in oedema volume (between day 1 and day 360) were not significant when compared to the pre-treatment (day 0) value. The percentage reduction at day 360 was only 9%, which was not significant (P > 0.05). CONCLUSION: This study has shown that Daflon (500 mg, twice a day for 90 days) is both safe and efficacious in reducing oedema volume in bancroftian filarial lymphoedema. Further clinical trials are essential for strengthening the evidence base on the role of this drug in the morbidity management of lymphatic filariasis.     

Direct intracardiac injection of umbilical cord-derived stromal cells and umbilical cord blood-derived endothelial cells for the treatment of ischemic cardiomyopathy

The development of new therapeutic strategies is necessary to reduce the worldwide social and economic impact of cardiovascular disease, which produces high rates of morbidity and mortality. A therapeutic option that has emerged in the last decade is cell therapy. The aim of this study was to compare the effect of transplanting human umbilical cord-derived stromal cells (UCSCs), human umbilical cord blood-derived endothelial cells (UCBECs) or a combination of these two cell types for the treatment of ischemic cardiomyopathy (IC) in a Wistar rat model. IC was induced by left coronary artery ligation, and baseline echocardiography was performed seven days later. Animals with a left ventricular ejection fraction (LVEF) of ≤40% were selected for the study. On the ninth day after IC was induced, the animals were randomized into the following experimental groups: UCSCs, UCBECs, UCSCs plus UCBECs, or vehicle (control). Thirty days after treatment, an echocardiographic analysis was performed, followed by euthanasia. The animals in all of the cell therapy groups, regardless of the cell type transplanted, had less collagen deposition in their heart tissue and demonstrated a significant improvement in myocardial function after IC. Furthermore, there was a trend of increasing numbers of blood vessels in the infarcted area. The median value of LVEF increased by 7.19% to 11.77%, whereas the control group decreased by 0.24%. These results suggest that UCSCs and UCBECs are promising cells for cellular cardiomyoplasty and can be an effective therapy for improving cardiac function following IC.     

A novel thermophilic pectate lyase containing two catalytic modules of Clostridium stercorarium

The Clostridium stercorarium F-9 pel9A gene encodes a pectate lyase Pel9A consisting of 1,240 amino acids with a molecular weight of 135,171. The mature form of Pel9A is a modular enzyme composed of two family-9 catalytic modules of polysaccharide lyases, CM9-1 and CM9-2, in order from the N terminus. Pel9A showed an overall sequence similarity to the hypothetical pectate lyase PelX of Bacillus halodurans (sequence identity 53%), and CM9-2 showed moderate sequence similarities to some pectate lyases of family 9. Sequence identity between CM9-1 and CM9-2 was 21.3%. The full-length Pel9A lacking the N-terminal signal peptide was expressed, purified, and characterized. The enzyme required Ca(2+) ion for its enzyme activity and showed high activity toward polygalacturonic acid but lower activity toward pectin, indicating that Pel9A is a pectate lyase. Immunological analysis using an antiserum raised against the purified enzyme indicated that Pel9A is constitutively synthesized by C. stercorarium F-9.     

All politics is local: the case of Macrocephalon maleo conservation on Sulawesi, Indonesia

The rich biodiversity of the Indonesian island of Sulawesi is subject to a high rate of deforestation and other pressures. Its plight is symbolized by the deteriorating conservation status of the maleo, an iconic galliform bird that is both striking in appearance and intimately bound up with local traditions. After a series of international-led projects during the 1980s and early 1990s conservation efforts petered out until recently when there has been an upsurge in local-led concern and action. To capitalize on this a workshop was held in 2010 to share local perceptions, lessons and concerns about the species and these conservation efforts. The workshop was dominated by members of local communities and their elected or traditional representatives, although there was also a wide variety of other stakeholders present, including from national species conservation and local government agencies. Whilst there is a need for more information to underpin the actions necessary to ensure the survival of this species, the overwhelming perception of participants was that continued decentralization of policy making and budgetary responsibility would enhance the conservation efforts for this species (and other elements of biodiversity) considerably. This would allow the upsurge in locally-led conservation activities to be continued and expanded.     

Sentulic acid: a cytotoxic ring A-seco triterpenoid from Sandoricum koetjape Merr

A new ring A-seco triterpenoid, sentulic acid, along with a known oleanane-type triterpenoid, 3-oxoolean-12-en-27-oic acid, were isolated from the Indonesian plant Sandoricum koetjape Merr. Their chemical structures were elucidated by spectroscopic analysis. In addition, the cytotoxic effects of these compounds on human promyelocytic leukemia HL-60 cells were studied. The results of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays and trypan blue dye exclusion tests showed that sentulic acid and 3-oxoolean-12-en-27-oic acid were able to induce cytotoxicity in these cells. Furthermore, morphological examination and DNA fragmentation analysis indicated that these cytotoxic effects were mediated by apoptosis.     

Structural analysis of protein tyrosine phosphatase 1B reveals potentially druggable allosteric binding sites

Catalytic proteins such as human protein tyrosine phosphatase 1B (PTP1B), with conserved and highly polar active sites, warrant the discovery of druggable nonactive sites, such as allosteric sites, and potentially, therapeutic small molecules that can bind to these sites. Catalyzing the dephosphorylation of numerous substrates, PTP1B is physiologically important in intracellular signal transduction pathways in diverse cell types and tissues. Aberrant PTP1B is associated with obesity, diabetes, cancers, and neurodegenerative disorders. Utilizing clustering methods (based on root mean square deviation, principal component analysis, nonnegative matrix factorization, and independent component analysis), we have examined multiple PTP1B structures. Using the resulting representative structures in different conformational states, we determined consensus clustroids and used them to identify both known and novel binding sites, some of which are potentially allosteric. We report several lead compounds that could potentially bind to the novel PTP1B binding sites and can be further optimized. Considering the possibility for drug repurposing, we discovered homologous binding sites in other proteins, with ligands that could potentially bind to the novel PTP1B binding sites.     

Cloning, sequencing, and expression of the gene encoding the Clostridium stercorarium alpha-galactosidase Aga36A in Escherichia coli

The alpha-galactosidase gene aga36A of Clostridium stercorarium F-9 was cloned, sequenced, and expressed in Escherichia coli. The aga36A gene consists of 2,208 nucleotides encoding a protein of 736 amino acids with a predicted molecular weight of 84,786. Aga36A is an enzyme classified in family 36 of the glycoside hydrolases and showed sequence similarity with some enzymes of family 36 such as Geobacillus (formerly Bacillus) stearothermophilus GalA (57%) and AgaN (52%). The enzyme purified from a recombinant E. coli is optimally active at 70 degrees C and pH 6.0. The enzyme hydrolyzed raffinose and guar gum with specific activities of 3.0 U/mg and 0.46 U/mg for the respective substrates.     

Shamanism, Psychosis and Autonomous Imagination

This paper focuses on traditional healers (balian)in Bali, Indonesia, to raise new argumentsconcerning the nature of the initiatory sufferingsreportedly experienced by shamans in many cultures.Our evidence suggests that a) contrary to ourexpectations, an initiatory madness or illness isexperienced by a minority rather than the majority ofbalian, and b) whether or not a balian undergoesinitiatory sufferings seems to be linked to gender andto the methods of healing employed – thus womenhealers who employ trance possession are those mostlikely to report an initiatory madness or illness.This leads to the central argument of the paper: c)the nature of the initiatory sufferings, where they dooccur, can be clearly distinguished on several groundsfrom the onset of mental illness among Balinese, bothemically in terms of cultural understandings, andetically in terms of objective criteria. Finally wediscuss the concept of ``autonomous imagination,'suggesting that the key to becoming a balian is notovercoming an initiatory madness but gaining controlover this special mode of imagery thought. We furthersuggest that Western ideas concerning the self andself healing, the superficial resemblance of theinitiatory sufferings to schizophrenia, and thedramatic nature of the initiatory sufferings when theyoccur, have combined to give a misleading prominenceto the role of an initiatory madness in shamanism.