Preceding standard therapy is the likely cause of MDS after autotransplants for multiple myeloma

Myelodysplastic syndromes (MDS) and acute myeloid leukaemia (AML) have been reported after autologous transplantation (AT) for lymphoma. It is not clear whether myeloablative therapy used in conjunction with autologous transplantation contributes to the development of MDS/AML or whether the conventional chemotherapy preceding the transplant, and administered over a prolonged period, causes these secondary malignancies. To address this issue, we examined 188 patients with multiple myeloma (MM) who had received AT. 71 patients with no more than one cycle of standard chemotherapy were enrolled in our Total Therapy program, designed to avoid exposure to alkylating agents prior to peripheral blood stem cell mobilization (group 1). The median duration of pre-transplant therapy in group 1 was 7.6 months and significantly shorter than the 24 months of 117 patients (group 2) with more prolonged conventional therapy ( P  = 0.0001). All seven patients developing MDS post-transplantation belonged to group 2 ( P  = 0.02); the median durations from initial therapy and first transplant were 66 months (range 38–86) and 24 months (range 9–39), respectively. Our findings provide evidence that prolonged standard-dose alkylating agent therapy prior to transplantation, rather than autotransplant-supported myeloablative treatment, is associated with development of MDS/AML. Stem cell damaging alkylator treatment should be avoided, not to compromise PBSC collection, but also to reduce the risk of treatment-related MDS/AML.     

Novel huperzine A based NMDA antagonists: insights from molecular docking,ADME/T and molecular dynamics simulation studies

Huperzine A (HupA) is an alkaloidal natural product and drug isolated from Chinese herb Huperzia serrata, which is a potent selective anticholinesterase inhibitor. HupA has symptomatic, cognitive-enhancing and protective effect on neurons against amyloid beta-induced oxidative injury and antagonizing N-methyl-d-aspartate receptors by blocking the ion channels. The present study aimed to identify the docking, ADME/T and molecular dynamics simulation parameters of a library of 40 analogues which can correlate the binding affinity, conformational stability and selectivity of the ligands towards NMDA receptor through in silico approach. Glide molecular docking analysis was performed for the designed analogues to understand the binding mode and interactions. MD simulations were performed to explain the conformational stability and natural dynamics of the interaction in physiological environmental condition of protein–ligand complex affording a better understanding of chemical-scale interactions between HupA and its analogues with NMDA channel that could potentially benefit the development of new drugs for neurodegenerative diseases involving NMDA receptors.

The in silico study explores the structural behavior and binding affinities of 40 novel analogues of huperzine A. Novel NMDA receptor antagonists have been virtually identified by molecular docking, ADME/T and molecular dynamics simulation studies.     

Minimising complications in abdominoplasty: An approach based on the root cause analysis and focused preventive steps

Significant complications still occur after abdominoplasty, the rate varies widely in different series. This variation suggests that there is a lot of scope for improvement. This paper reviews the various complications and also the technical improvements reported in the last 20 years. The root cause of each complication is analysed and preventive steps are suggested based on the literature and the author''s own personal series with very low complication rates. Proper case selection, risk stratified prophylaxis of thromboembolism, initial synchronous liposuction, flap elevation at the Scarpa fascia level, discontinuous incremental flap dissection, vascular preservation and obliteration of the sub-flap space by multiple sutures emerge as the strongest preventive factors. It is proposed that most of the complications of abdominoplasty are preventable and that it is possible to greatly enhance the aesthetic and safety profile of this surgery.KEY WORDS: Abdominoplasty, complications, diastasis recti, haematoma, lipoabdominoplasty, necrosis, seroma, venous thromboembolism, ventral hernia, wound dehiscence     

Biosynthesis of the Pseudomonas polyketide coronafacic acid requires monofunctional and multifunctional polyketide synthase proteins

Coronafacic acid (CFA) is the polyketide component of the phytotoxin coronatine, a virulence factor of the plant pathogen Pseudomonas syringae. Our current knowledge of polyketide biosynthesis largely is based on the analysis of polyketide synthases (PKSs) in actinomycetes and other Gram-positive bacteria. Consequently, the cloning and characterization of the CFA biosynthetic gene cluster will contribute significantly to our knowledge of polyketide synthesis in Pseudomonas. In this report, we describe two genes in the CFA biosynthetic gene cluster that encode PKSs that are structurally and functionally similar to the multifunctional modular PKSs, which catalyze the synthesis of macrolide antibiotics. The CFA PKS genes were overproduced in Escherichia coli and shown to cross-react with antisera made to a modular PKS involved in erythromycin synthesis. A scheme for CFA biosynthesis is presented that incorporates the activities of all proteins in the CFA PKS. In this report a gene cluster encoding a pseudomonad polyketide has been completely sequenced and the deduced gene functions have been used to develop a biosynthetic scheme.     

Plasmacytoid variant of myoepithelioma of palate: a case report

Myoepitheliomas of intraoral minor salivary glands are rare and are usually of plasmacytoid type. Myoepitheliomas are considered difficult to diagnose without the aid of ultrastructural and histochemical studies. Here we present a case report of plasmacytoid type of myoepithelioma of palate that was diagnosed by light microscopic examination alone. Considering the non-specificity of ultrastructural and histochemical findings, it is important to pay attention to typical features of plasmacytoid myoepitheliomas to arrive at a diagnosis.     

Laparoscopic vaginoplasty: using a sliding peritoneal flap for correction of complete vaginal agenesis

In this technique of peritoneal neo-vaginoplasty, the recto-vesical space is dissected through the vulva under synchronous laparoscopic monitoring. Then the cranial limit of the pelvic peritoneum is incised circumferentially by laparoscopic approach and the two circular edges sutured sequentially. The isolated pelvic peritoneal sleeve is opened inferiorly and sutured to introital mucosal flaps.