Amino acid conjugated sophorolipids: A new family of biologically active functionalized glycolipids

Sophorolipids (SLs) are extra cellular glycolipids produced by Candida bombicola ATCC 22214 when grown in the presence of glucose and fatty acids. These compounds have a disaccharide head group connected to a long-chain hydroxyl-fatty acid by a glycosidic bond. To explore structure-activity of modified SLs, a new family of amino acid-SL derivatives was prepared. Synthesized analogs consist of amino acids linked by amide bonds formed between their alpha-amino moiety and the carboxyl group of ring-opened SL fatty acids. Their preparation involved the following: (i) hydrolysis of a natural SL mixture with aqueous alkali to give SL free acids, (ii) coupling of free acids to protected amino acids using dicarbodiimide, and (iii) removing amino acid carboxyl protecting groups. These conjugates were evaluated for their antibacterial, anti-HIV, and spermicidal activity. All tested analogs showed antibacterial activity against both gram +ve and gram -ve organisms. Leucine-conjugated SL was most efficient. For example, the minimum inhibitory concentrations (MIC) for Moraxella sp. and E. coli were 0.83 and 1.67 mg/mL, respectively. Among the alkyl esters of amino acid conjugated SLs, the ethyl ester of leucine-SLs was most active. Against Moraxella sp., S. sanguinis, and M. imperiale, MIC values are 7.62 x 10(-4), 2.28 x 10-(3) and 1.67 mg/mL, respectively. All compounds displayed virus-inactivating activity with 50% effective concentrations (EC50) below 200 microg/mL. The EC50 of leucine-SL ethyl ester was 24.1 microg/mL, showing that it is more potent than commercial spermicide nonoxynol-9 (EC50 approximately 65 microg/mL).     

Classification of large array surface myoelectric potentials from subjects with and without low back pain.

An algorithm was developed and tested for differentiating between the spatial distribution of large arrays of surface electromyographic (LASE) data from subjects with and without low back pain (LBP). The surface EMG data from 62 channels were collected from the low back of 161 healthy and 44 acute (less than 6-weeks) LBP subjects in three minimum stress postural positions including standing, 20 degrees of trunk flexion (at hip joint) and standing with arms extended forward holding a 1.36kg (3lb) weight in each hand. These data were statistically analyzed and the spatial distribution of the root mean square (RMS) values was used in a multivariate quadratic discriminant model to reclassify the healthy and acute LBP subjects. The most predictive results were obtained from the 'flexion' group of experiments and correctly reclassified 95.5% (42/44) of the acute LBP subjects and 99.4% (160/161) of the healthy subjects. The success rate of this reclassification based on surface distribution of myoelectric potentials was found to be better than the reported patient classifications based on a smaller set of electrode pairs using fewer subjects [Peach JP, McGill SM, Classification of low back pain with use of spectral electromyogram parameters. Spine 23(10):1998;1117-23; Roy SH, De Luca CJ, Emley M, Oddsson LI, Buijs RJ, Levins JA, Newcombe DS, Jabre JF. Classification of back muscle impairment based on the surface electromyographic signal. J Rehabil Res Dev 34(4):1997;405-14 [review]]. The results indicated the potential of the model for clinical patient classification.     

Persisters: a distinct physiological state of E. coli

Background  

Bacterial populations contain persisters, phenotypic variants that constitute approximately 1% of cells in stationary phase and biofilm cultures. Multidrug tolerance of persisters is largely responsible for the inability of antibiotics to completely eradicate infections. Recent progress in understanding persisters is encouraging, but the main obstacle in understanding their nature was our inability to isolate these elusive cells from a wild-type population since their discovery in 1944.     

Secondary penile tumours revisited

Objective

To highlight the salient features of metastatic malignancies involving the penis, with special reference to the primary tumour sites, metastatic mechanisms, clinical features, differential diagnosis, treatment and prognosis.

Methods

A comprehensive search of the literature was performed using MEDLINE and EMBASE, using the keywords 'penis', 'secondary malignancy', 'metastasis' and 'malignant priapism' to identify reviews and case reports of secondary penile malignancy. A case of rare clinical presentation of metastatic penile lesion is presented along with the review of the literature.

Conclusion

Secondary malignancy of the penis is a rare clinical entity, despite the rich vascularisation of this organ. The majority of metastatic lesions take their origin from the neighbouring genito-urinary organs, mainly prostate and bladder. These lesions are often associated with disseminated malignancy and hence have a poor outcome. Nodular or ulcerative lesions involving the corpora cavernosa or priapism are the main modes of clinical presentation. In most cases, only palliative or supportive therapy is indicated.

     

Influence of network structure on the degradation of photo-cross-linked PLA-b-PEG-b-PLA hydrogels

Triblock copolymers of functionalized poly(lactic acid)-b-poly(ethylene glycol)-b-poly(lactic acid) (PLA-b-PEG-b-PLA) have been widely investigated as precursors for fabricating resorbable polymeric drug delivery vehicles and tissue engineering scaffolds. Previous studies show degradation and erosion behavior of PLA-b-PEG-b-PLA hydrogels to rely on macromer chemistry as well as structural characteristics of the cross-linked networks. In this research, the degradation kinetics of diacrylated PLA-b-PEG-b-PLA copolymers as soluble macromers and cross-linked gels are directly compared as a function of macromer concentration, buffer pH, and ionic strength. The pseudo first-order rate constants for degradation of soluble macromers increase with water concentration and show a minimum at intermediate pH values, but are insensitive to ionic strength. The degradation rate constants for covalently cross-linked gels display a greater sensitivity to local water concentration and a minimum at lower pH values than corresponding soluble macromers. In addition, ionic strength significantly affects the rate of gel degradation due to the direct correlation between the degree of network ionization and gel water content.     

Atypical D-FISH patterns of BCR/ABL gene rearrangements in 169 chronic myeloid leukemia patients

The Philadelphia (Ph) chromosome, a hallmark chromosomal anomaly observed in 95 percent of chronic myeloid leukemia (CML) cases, is known to involve the Abelson (ABL) proto-oncogene on chromosome 9 and the breakpoint cluster region (BCR) gene on chromosome 22, producing BCR/ABL mRNA encoding an abnormal tyrosine kinase protein. In the process of generating BCR-ABL fusion, the deletion of residual BCR or ABL occurs in 15-30 percent of CML patients. In addition, some rearrangements are complex, and do not yield the ABL/BCR fusion due to the involvement of a third chromosome in the rearrangement. The possible role of these deletions and complex rearrangements in disease outcome is an ongoing topic of research. We report our results of cytogenetic analysis with GTG banding and fluorescence in situ hybridization using dual color dual fusion probe (D-FISH) from Vysis Inc, USA in 169 (109 male and 60 female) CML patients registered at The Gujarat Cancer and Research Institute (GC and RI) from April 2004 to December 2005. GTG banding was carried out in 123 cases having analyzable metaphases. Of these 123 cases, D-FISH revealed atypical signal patterns in 57 patients (46%), and 12 cases revealed additional complex translocations indicative of disease progression. Out of 57 cases with atypical FISH patterns, 22 included metaphase FISH results, and the rest had only interphase FISH performed. In addition to the hallmark Philadelphia chromosome, other chromosomal aberrations in CML revealed heterogeneity of molecular events. Pooling of more data may lead to identification of new CML sub-groups and hence help in the analysis of clinical trials. Patients enrolled in our prospective study of prognostic significance will be followed up for disease free and overall survival in correlation with ABL-BCR deletion status.     

A Technique for Simultaneous Antikinetochore Immunofluorescence Staining and Q-Banding in Chromosomes from Human Lymphocytes

Antikinetochore immunofluorescence staining has been used in several studies to determine whether a second kinetochore is present, active, or both, in multicentric chromosomes. All of these studies have used tissue culture cells, and contended with the problem of obtaining well spread, banded metaphase chromosomes without affecting the kinetochore staining. We have adapted hypotonic, centrifugation and chromosome staining techniqnes to obtain simultaneous Q-banding and bright kinetochore staining of chromosomes from human lymphocytes.     

Time and money in pediatric practice

The types of services provided by pediatricians in Ontario and the payment they received from OHIP for a three-month period in 1972 are examined. Pediatricians provided 4.8% of the total of 16.3 million services and received 3.3% of the total $117.7 million payment. Most of the services were provided in ambulatory settings. Skin testing for allergy and hyposensitization accounted for 42% of the total of pediatric services. More than two thirds of pediatricians were engaged in provision of services which could be classified as primary care. Indeed, most of the services provided were of a primary care nature.There is a pressing need for redifining the pediatrician''s role in our health-care delivery system and for a new look at his education.