Selective Cytotoxicity and Combined Effects of Camptothecin or Paclitaxel with Sodium-R-Alpha Lipoate on A549 Human Non-Small Cell Lung Cancer Cells

Nonsmall cell lung cancer (NSCLC) is the most common type of lung cancer and remains the deadliest form of cancer in the United States and worldwide. New therapies are highly sought after to improve outcome. The effect of sodium-R-alpha lipoate on camptothecin- and paclitaxel-induced cytotoxicity was evaluated on A549 NSCLC and BEAS-2B “normal” lung epithelial cells. Combination indices (CI) and dose reduction indices (DRI) were investigated by studying the cytotoxicity of sodium-R-alpha lipoate (0–16 mM), camptothecin (0–25 nM) and paclitaxel (0–0.06 nM) alone and in combination. 3-(4,5-dimethylthiazol-2-Yl)-2,5-diphenyltetrazolium-bromide (MTT) was used to assess cytotoxicity. The combinational cytotoxic effects of sodium-R-alpha lipoate with camptothecin or paclitaxel were analyzed using a simulation of dose effects (CompuSyn® 3.01). The effects of sodium-R-alpha lipoate on camptothecin- and paclitaxel-induced cytotoxicity varied based on concentrations and treatment times. It was found that sodium-R-alpha lipoate wasn't cytotoxic toward BEAS-2B cells at any of the concentrations tested. For A549 cells, CIs [(additive (CI = 1); synergistic (CI < 1); antagonistic (CI < 1)] were lower and DRIs were higher for the camptothecin/sodium-R-alpha-lipoate combination (CI = ～0.17–1.5; DRI = ～2.2–22.6) than the paclitaxel/sodium-R-alpha-lipoate combination (CI = ～0.8–9.9; DRI = ～0.10–5.8) suggesting that the camptothecin regimen was synergistic and that the addition of sodium-R-alpha lipoate was important for reducing the camptothecin dose and potential for adverse effects.     

Contribution of different mechanisms to the resistance to fluoroquinolones in clinical isolates of Salmonella enterica

ObjectivesTo study the potential factors include gene mutation, efflux pump and alteration of permeability associated with quinolone-resistance of Salmonella enterica strains isolated from patients with acute gastroenteritis and to evaluate the degree of synergistic activity of efflux pump inhibitors when combined with ciprofloxacin against resistant isolates.MethodsAntimicrobial resistance patterns of fifty-eight Salmonella isolates were tested. Five isolates were selected to study the mechanism of resistance associated with quinolone group, including mutation in topoisomerase-encoding gene, altered cell permeability, and expression of an active efflux system. In addition, the combination between antibiotics and efflux pump inhibitors to overcome the microbial resistance was evaluated.ResultsFive Salmonella isolates totally resistant to all quinolones were studied. All isolates showed alterations in outer membrane proteins including disappearance of some or all of these proteins (Omp-A, Omp-C, Omp-D and Omp-F). Minimum inhibitory concentration values of ciprofloxacin were determined in the presence/absence of the efflux pump inhibitors: carbonyl cyanide m-chlorophenylhydrazone, norepinephrin and trimethoprim. Minimum inhibitory concentration values for two of the isolates were 2–4 fold lower with the addition of efflux pump inhibitors. All five Salmonella isolates were amplified for gyrA and parC genes and only two isolates were sequenced. S. Enteritidis 22 had double mutations at codon 83 and 87 in addition to three mutations at parC at codons 67, 76 and 80 whereas S. Typhimurium 57 had three mutations at codons 83, 87 and 119, but no mutations at parC.ConclusionsEfflux pump inhibitors may inhibit the major AcrAB-TolC in Salmonella efflux systems which are the major efflux pumps responsible for multidrug resistance in Gram-negative clinical isolates.     

Effets de Capsicum frutescens L. (Solanaceae) et de Zingiber officinale (Zingiberaceae) sur la croissance de Phoma sabdariffae (Phomaceae) au Gabon

Phoma sabdariffae is the main roselle pathogenic fungus agent in Gabon. The present study was undertaken in order to experiment a biological strategy to eradicate this pathology. Hence, spice and ginger essential oils were extracted (rotavapor) and incorporated in PDA medium, constituting 3 concentrated (1/4, 1/2 and 3/4) samples. Fungus growth was measured after culture with a gradual ruler. The results showed all spice and ginger extracts inhibited significantly Phoma sabdariffae mycelium growth. Fungus inhibition rates were proportional to plant extracts’ concentrations. But for a same concentration the effects between the 2 plants’ essential oils weren’t different. Hence, the use of spice- and ginger-concentrated crude extracts may be envisaged against Phoma sabdariffae pathogenic agent.     

Amebic Liver Abscess: Changing Trends over 20 Years RID="" ID="" This study was presented to the Turkish Surgical Congress in Izmir, Turkey.

RID=" ID=" <E5>Correspondence to:</E5> Y. Akgun, M.D.     

Surgical treatment of infective valve endocarditis in children with congenital heart disease

Abstract Objective: This study assesses surgical procedures, operative outcome, and early and intermediate‐term results of infective valve endocarditis in children with congenital heart disease. Methods: Seven consecutive children (five females, two males; mean age, 10.8 years) who underwent surgery for infective valve endocarditis between 2006 and 2010 were included in the study. The aortic and mitral valves were affected in two and tricuspid in five patients. Indications for operation included cardiac failure due to atrioventricular septal rupture, severe tricuspid valve insufficiency, and septic embolization in one, moderate valvular dysfunction with vegetations in three (two tricuspid, one mitral), and severe valvular dysfunction with vegetations in the other three patients (two tricuspid, one mitral). The pathological microorganism was identified in five patients. Tricuspid valve repair was performed with ventricular septal defect (VSD) closure in five patients. Two patients required mitral valve repair including one with additional aortic valve replacement. Results: There were no operative deaths. Actuarial freedom from recurrent infection at one and three years was 100%. Early echocardiographic follow‐up showed four patients to have mild atrioventricular valve regurgitation (three tricuspid and one mitral) and three had no valvular regurgitation. No leakage from the VSD closure or any valvular stenosis was detected postoperatively. Conclusions: Mitral and tricuspid valve repairs can be performed with low morbidity/mortality rates and satisfactory intermediate‐term results in children with infective valve endocarditis . (J Card Surg 2012;27:93‐98)     

Arachnoiditis ossificans of the cauda equina

A case of post-traumatic arachnoiditis ossificans of the cauda equina is reported. The lesion is a rare pathological entity usually confined to the thoracic and high lumbar regions that can cause progressive spinal cord and cauda equine compression. The pathophysiology and therapeutic strategy of this rare entity are still controversial.     

Selecting a Surgical Modality to Treat a Splenic Hydatid Cyst: Total Splenectomy or Spleen-Saving Surgery?

Aim

We analyzed the outcomes and effectiveness of surgical treatments and clinical manifestations of splenic hydatid cysts.

Patients and Methods

Between 2000 and 2011, we retrospectively reviewed the cases of 11 patients who were operated on for a splenic hydatid cyst. The demographic features, medical history, physical examinations, biochemical and serological tests, imaging modalities, and surgical treatment of the patients were noted.

Results

The mean patient age was 36.45?years (range, 20?C66?years). While isolated splenic hydatid disease was present in five patients, other abdominal hydatid cysts were accompanied by a splenic hydatid cyst in six patients. Left upper abdominal pain was present in seven (64%) patients, whereas four (36%) patients were asymptomatic. Eight patients (72.72%) had undergone a total splenectomy and three (27.28%) had undergone spleen-preserving surgery. Postoperative complications developed in four (36%) patients at 5?C15?days postoperatively.

Conclusion

Management of a splenic hydatid cyst is not consensual. Total splenectomy is optimal because it provides definitive treatment. However, spleen-preserving surgery is the preferred treatment in selected patients. The choice of technique depends on the localization, number, and size of hydatid cysts, and the absence or presence of other hydatic organ cysts.