Antimicrobial activities of novel bipyridine compounds produced by a new strain of Saccharothrix isolated from Saharan soil

The actinobacterium strain ABH26 closely related to Saccharothrix xinjiangensis, isolated from an Algerian Saharan soil sample, exhibited highly antagonist activity against Gram-positive bacteria, yeasts and filamentous fungi. Its ability to produce antimicrobial compounds was investigated using several solid culture media. The highest antimicrobial activity was obtained on Bennett medium. The antibiotics secreted by strain ABH26 on Bennett medium were extracted by methanol and purified by reverse-phase HPLC using a C18 column. The chemical structures of the compounds were determined after spectroscopic (¹H NMR, ¹³C NMR, ¹H-¹H COSY and ¹H-¹³C HMBC spectra), and spectrometric (mass spectrum) analyses. Two new cyanogriside antibiotics named cyanogriside I (1) and cyanogriside J (2), were characterized along with three known caerulomycins, caerulomycin A (3), caerulomycin F (4) and caerulomycinonitrile (5). This is the first report of cyanogrisides and caerulomycins production by a member of the Saccharothrix genus. The minimum inhibitory concentrations (MIC) of these antibiotics were determined against pathogenic microorganisms.     

Reliability and longevity of implantable defibrillators

Journal of Interventional Cardiac Electrophysiology - We hypothesized that data in manufacturers’ product performance reports (PPRs) can provide clinically valuable ICD and cardiac...     

Senescence-initiated reversal of drug resistance: specific role of cathepsin L

The present study was undertaken to verify whether induction of senescence could be sufficient to reverse drug resistance and, if so, to determine the underlying mechanism(s). Our findings indicated that cotreatment of drug-resistant neuroblastoma cells with doxorubicin, at sublethal concentrations, in combination with the pan-caspase inhibitor, Q-VD-OPH, elicited a strong reduction of cell viability that occurred in a caspase-independent manner. This was accompanied by the appearance of a senescence phenotype, as evidenced by increased p21/WAF1 expression and senescence-associated beta-galactosidase activity. Experiments using specific inhibitors of major cellular proteases other than caspases have shown that inhibition of cathepsin L, but not proteasome or cathepsin B, was responsible for the senescence-initiated reversal of drug resistance. This phenomenon appeared to be general because it was valid for other drugs and drug-resistant cell lines. A nonchemical approach, through cell transfection with cathepsin L small interfering RNA, also strongly reversed drug resistance. Further investigation of the underlying mechanism revealed that cathepsin L inhibition resulted in the alteration of intracellular drug distribution. In addition, in vitro experiments have demonstrated that p21/WAF1 is a substrate for cathepsin L, suggesting that inhibition of this enzyme may result in p21/WAF1 stabilization and its increased accumulation. All together, these findings suggest that cathepsin L inhibition in drug-resistant cells facilitates induction of senescence and reversal of drug resistance. This may represent the basis for a novel function of cathepsin L as a cell survival molecule responsible for initiation of resistance to chemotherapy.     

The epidemiology of methicillin-resistant Staphylococcus aureus at a Saudi university hospital

To determine changes in the epidemiology of methicillin-resistant Staphylococcus aureus (MRSA), a prospective study was conducted for a 30-month period in a university hospital in the eastern province of Saudi Arabia. Of 1,096 Staphylococcus aureus isolates identified, 92 (8.4%) were MRSA. Seventy-two (78%) of the 92 isolates were from nosocomial cases and 20 (22%) isolates were from community cases. Thirteen (14%) of 20 patients with community-acquired MRSA had no discernible risk factors. The community-acquired MRSA from patients without identified risk were susceptible to a greater number of antimicrobials compared with isolates obtained from patients with community-acquired MRSA with identified risk or with nosocomially acquired MRSA. No strain resistant to vancomycin was recorded in this study. The impact of these organisms could be substantial if they become more frequent or widespread.     

The Thymus Contains a High Frequency of Cells that Prevent Autoimmune Diabetes on Transfer into Prediabetic Recipients

Rats of the PVG.RT1^u strain develop autoimmune diabetes when thymectomized at 6 wk of age and are rendered relatively lymphopenic by a cumulative dose of 1,000 rads ¹³⁷Cs γ-irradiation given in four split doses. Previous studies have shown that the disease is prevented by the intravenous injection of 5 × 10⁶ CD4⁺ CD45RC⁻ TCRαβ⁺ RT6⁺ peripheral T cells from normal syngeneic donors. These cells have a memory phenotype and are presumably primed to some extrathymic antigen. However, we now report that the CD4⁺ CD8⁻ population of mature thymocytes is a very potent source of cells, with the capacity to prevent diabetes in our lymphopenic animals. As few as 6 × 10⁵ of these cells protect ~50% of recipients and the level of protection increases with cell dose. It appears that one characteristic of the intrathymic selection of the T cell repertoire is the generation of cells that regulate the autoimmune potential of peripheral T cells that have been neither clonally deleted intrathymically nor rendered irreversibly anergic in the periphery.     

Doxorubicin-induced apoptosis in caspase-8-deficient neuroblastoma cells is mediated through direct action on mitochondria

The induction of p53 expression and stimulation of the Fas/caspase-8 pathway represent major mechanisms by which cytotoxic drugs induce apoptosis, but in neuroblastomas, the caspase-8 gene is often not expressed. Purpose: The aim of this study was to determine whether doxorubicin could induce apoptosis in caspase-8-deficient neuroblastoma cells and to define its mechanism of action. Methods: The caspase-8-deficient human neuroblastoma cell line, SKN-SH, was incubated with doxorubicin and the apoptotic response, as well as expression of apoptotic molecules in the p53/Fas/caspase-8 pathway, were determined. Results: SKN-SH cells incubated with doxorubicin readily underwent apoptosis in a concentration-dependent manner. Western blot analyses with specific antibodies demonstrated that both p53 and Fas ligand were endogenously expressed in SKN-SH cells, but their expression was not stimulated by doxorubicin. Fas receptor was not detected in these cells and caspase-8 was totally absent. Electron microscopic analyses of SKN-SH cells treated with doxorubicin revealed pronounced alterations in mitochondrial structure. This treatment also induced the release of cytochrome c from mitochondria and activated the downstream apoptotic intermediate, caspase-3. Conclusion: These results indicate that the p53/Fas/caspase-8 system does not play a role in mediating the apoptotic action of doxorubicin in the human neuroblastoma cell line SKN-SH. Thus, mitochondria and downstream apoptotic signaling intermediates may be considered as key targets for doxorubicin-induced apoptosis in neuroblastoma tumors having deficiencies in the Fas/caspase-8 system.     

Desmoplastic trichoepithelioma nosology. Reappraisal about a case developed on a varicella scar

We report the case of a 51-year-old woman who presented with a progressive elevation of the border of an old varicella scar. The lesion which was clinically diagnosed as a basal cell carcinoma turned out to be a typical desmoplastic trichoepithelioma. The development of desmoplastic trichoepithelioma in an area of scarring has not been previously reported. The nosology of this tumor is discussed with particular emphasis on its possible relationship to morphoeic basal cell carcinoma, thus questioning it as a true tumor sui generis.