Miconazole and terbinafine induced reactive oxygen species accumulation and topical toxicity in human keratinocytes.

There are an estimated 1 billion cases of superficial fungal infection globally. Fungal pathogens form biofilms within wounds and delay the wound healing process. Miconazole and terbinafine are commonly used to treat fungal infections. They induce the accumulation of reactive oxygen species (ROS) in fungi, resulting in the death of fungal cells. ROS are highly reactive molecules, such as oxygen (O2), superoxide anion (O2•-), hydrogen peroxide (H2O2) and hydroxyl radicals (•OH). Although ROS generation is useful for killing pathogenic fungi, it is cytotoxic to human keratinocytes. To the best of our knowledge, the effect of miconazole and terbinafine on HaCaT cells has not been studied with respect to intracellular ROS stimulation. We hypothesized that miconazole and terbinafine have anti-wound healing effects on skin cells when used in antifungal treatment because they generate ROS in fungal cells. We used sulforhodamine B protein staining to investigate cytotoxicity and 2',7'-dichlorofluorescein diacetate to determine ROS accumulation at the 50% inhibitory concentrations of miconazole and terbinafine in HaCaT cells. Our preliminary results showed that topical treatment with miconazole and terbinafine induced cytotoxic responses, with miconazole showing higher cytotoxicity than terbinafine. Both the treatments stimulated ROS in keratinocytes, which may induce oxidative stress and cell death. This suggests a negative correlation between intracellular ROS accumulation in keratinocytes treated with miconazole or terbinafine and the healing of fungi-infected skin wounds.

Synthesis of hexahydrofuro[3,2-c]quinoline, a martinelline type analogue and investigation of its biological activity.

BACKGROUND: Candida susceptibility commonly occurs in breast cancer patients. Of which, Candida albicans is considered as a common pathogen causing candidiasis. Martinella iquitosensis (Bignoniaceae) is one of the species belonged to Martinella, distributed widely in Amazon basin. Its root extract yielded two complex substituted tetrahydroquinolines, Martinelline and Martinellic acid which were the first natural non-peptide bradykinin receptor antagonists identified. FINDINGS: In this study, a novel martinelline type analogue, named 2,3,3a,4,5,9b-hexahydro-8-phenoxy-4-(pyridin-2-yl)furo[3,2-c]quinoline, was synthesized and its preliminary anticancer activity and antifungal potential were investigated. This compound showed potential anticancer activity against MDAMB-231 breast cancer cells. Meanwhile it could enhance the fungistatic activity of miconazole against Candida albicans. CONCLUSIONS: These findings provide an implication for the continue investigation and development of martinelline type analogues as therapeutic agents in the future.

Comparison between an accelerometer and a three-dimensional motion analysis system for the detection of movement.

OBJECTIVE: To examine the reliability and concurrent validity of an accelerometer compared with a three-dimensional (3D) motion analysis system for measuring the motor reaction time of the lower limbs, to validate a simple method for objective clinical assessment of movement onset. DESIGN: Timing of the onset of knee extension movement in response to an audio signal was measured simultaneously with an accelerometer and a 3D VICON motion analysis system. PARTICIPANTS: Twelve able-bodied subjects with a mean age of 26 (standard deviation 2.3) years. RESULTS: Good reliability was found for both instruments, although the intraclass correlation coefficient (ICC) was higher for the accelerometer (ICC3,1=0.739; P<0.001). The mean motor reaction time measured by the accelerometer and the VICON system was 205.0 and 196.9 mseconds, respectively. Good agreement was found between the paired measurements (mean ICC=0.774), and the average 95% limits of agreement were -56.4 to 72.5 mseconds. CONCLUSION: In conclusion, the accelerometer had good reliability for the measurement of movement onset time. Agreement between the measurements from the accelerometer and the VICON system was high. However, the limits of agreement covered a wide range, so absolute timings for movement onset derived from these methods should not be used interchangeably.

Association between preoperative allograft function (effective renal plasma flow) and the change in glomerular filtration rate among living-donor kidney transplant recipients.

BACKGROUND: Predonation kidney function may be an important factor affecting graft outcome. Increased baseline allograft function may be more effective than strategies to slow the decline in glomerular filtration rate (GFR). However, the role of donor effective renal plasma flow (ERPF) on long-term outcome is less well understood. The purpose of this study was to examine the relationship between preoperative allograft function as measured by ERPF and the decline of allograft function as defined by the annualized change in GFR among living-donor kidney transplant recipients. METHODS: We performed a retrospective analysis of 83 patients who underwent living donor renal transplantation at our institution from March 2001 to October 2010. A time series analysis of autoregressive integrated moving average (ARIMA) model was applied to determine the annualized change in GFR after transplantation. Univariate and stepwise multivariate analyses were performed using linear regression between preoperative ERPF and annualized change in GFR after transplantation. We also investigated the influence on annualized change in GFR of other donor or recipient variables. RESULTS: The ARIMA model revealed that the annualized change in GFR was -1.344 ± 12.476 mL/min/1.73 m(2) per year. Pearson correlation coefficient for the association between predonation ERPF of the transplanted kidney and the annualized change in GFR was 0.033 (P = .777). CONCLUSIONS: Poor predonation kidney function was not associated with an increased rate of decline of allograft function. Neither donor age nor renal function (preoperative ERPF value) was a valid predictor of change in GFR among living-donor kidney transplant recipients.

Influence of preoperative allograft function (effective renal plasma flow) on the short-term outcome following living donor kidney transplantation.

OBJECTIVES: Predonation kidney function is supposed to be an important factor affecting graft outcome. Controversial evidence suggests that higher predonation glomerular filtration rate (GFR) positively correlated with posttransplant graft outcome. The purpose of this study was to examine the relationship between living donor graft kidney function as measured by effective renal plasma flow (ERPF) and short-term graft function. METHODS: We performed a retrospective analysis of 45 patients who underwent living donor renal transplantation at our institution from 2001 to 2007. The comprehensive nuclear medicine evaluation of donors' ERPF was performed before laparoscopic nephrectomy. The preoperative absolute ERPF-recipient body surface area (F/BSA) ratio and absolute ERPF-recipient body weight (F/Wt) ratio were determined for each donor-recipient pair. Posttransplant graft function was estimated by the four-variable Modification of Diet in Renal Disease (Chinese MDRD) equation. RESULTS: Estimated GFR correlated with F/BSA ratio at 3 months and 6 months (Pearson r = .495, P = .001 and r = .441, P = .012). Estimated GFR correlated with F/Wt ratio at 3 months and 6 months (r = .567, P < .001 and r = .453, P = .009). The correlations between the estimated GFR at 3 months and other variables were investigated. However, in the final multivariate model, F/BSA ratio and F/Wt ratio were the independent predictors of graft function. CONCLUSION: Preoperative ERPF can be used to calculate F/BSA and F/Wt ratios before living donor kidney transplantation. Our study provided evidence that F/BSA and F/Wt ratios may be considered predictive indices for short-term outcomes. An extreme discrepancy should be avoided between preoperative allograft function (absolute ERPF) and recipient body surface area or body weight.

Five-year experience of adoption and evolution of laparoscopic living donor nephrectomy: results from a center without large volume of patients.

OBJECTIVES: Despite the advantages of laparoscopic living donor nephrectomy (LDN), this technique is known to have a steep learning curve that makes worldwide adoption challenging, especially in institutions without a large patients volume. Herein, we have reviewed our 5-year experience of adoption and evolution of this surgical technique, examining the donor and recipient outcomes. METHODS: Between September 2002 and June 2007, 40 LDNs were performed consecutively. Our surgical technique was mainly derived from the University of California San Francisco method. We retrospectively reviewed the donor demographics, operative characteristics, perioperative complication of donors/recipients, and outcomes of donors and recipients. RESULTS: Among the 40 cases, 36 (90.0%) were left-sided LDNs. Mean operative time was 335.1 +/- 66.9 minutes, blood loss was 303.9 +/- 333.2 mL, and warm ischemia time was 243.2 +/- 127.0 seconds. Multiple renal arteries required bench arterial reconstruction in 7 (17.5%) donor kidneys. Three renovascular injuries occurred intraoperatively, and 2 (5.0%) required open conversion. The overall postoperative complication rate was 20.0%. Postoperative donor serum creatinine was 1.5 times higher than preoperative serum creatinine. All but one recipient was discharged with adequate renal function. Graft function continues in 36 of the 38 harvested kidneys (94.7%) during the follow-up period. One (2.5%) recipient developed ureteral necrosis, and no recipients developed vascular thrombosis. CONCLUSIONS: LDNs can be performed with careful adoption and evolution in institutions without a large patient volume. The intraoperative complication rate of LDN can be reduced with experience.

Evolving medical therapies for ulcerative colitis.

Patients with ulcerative colitis have traditionally relied on sulfasalazine, mesalamine, and corticosteroids as the mainstay of medical therapy. Steroid-refractory, -dependent, or -intolerant patients have resorted to agents such as cyclosporine for short-term efficacy and 6-mercaptopurine or azathioprine for long-term efficacy. The next generation of evolving therapies includes many novel agents that target various aspects of the human immune response. Therapies that block the production or action of tumor necrosis factor have received much interest in inflammatory bowel disease. Treatments currently under study include interleukins, interferons, T-cell selective antibodies, molecules involved in cellular trafficking and signaling, mucosal healing or growth factors, and novel steroid agents. Other "less traditional" therapies, including probiotics, heparins, and anti-gastric ulcer remedies, challenge our understanding of the pathogenesis of ulcerative colitis and may provide further insights into future therapies.

Antibiotics in inflammatory bowel disease.

The use of antibiotics as primary therapy in inflammatory bowel disease (IBD) has been an issue of great controversy among the experts in the field. Although the utility of certain antimicrobial agents in managing secondary complications, such as abscess formation, toxic megacolon and pouchitis, has been substantiated by clinical trials, clear evidence to support or undermine their use as primary therapeutic agents in IBD is lacking. This may be secondary to the fact that the etiology of IBD remains unknown, and, despite much speculation and research in the area, no infectious agent has been found to cause or contribute to the pathogenesis of these disorders. The dearth of data, in turn, has resulted in widely varying treatment strategies and a lack of a clear standard of care with regard to the use of antibiotics.

Five-year results of a randomized, prospective, clinical trial of diode vs argon laser trabeculoplasty for open-angle glaucoma.

PURPOSE: To evaluate the safety and efficacy of laser trabeculoplasty (LTP) with a semiconductor diode laser (810 nm, [DLT]) vs an argon blue-green laser (488 to 514 nm, [ALT]). METHODS: In a prospective, randomized clinical trial, 50 eyes of 46 patients with uncontrolled open-angle glaucoma on maximally tolerated medical therapy were treated and followed at regular intervals for 5 years. Fifty laser spots were applied over 180 degrees using either maximal laser power or sufficient power to produce blanching or a small bubble (570 to 850 mW, DLT; 400 to 1,100 mW, ALT). We performed DLT using a 100-microm spot size, a 0.5-second exposure, and a Ritch lens; we conducted ALT with a 50-microm spot, a 0.1-second exposure, and a Goldmann lens. Patients in the study were followed until trabeculectomy was required. RESULTS: The mean follow-up times +/- SD for all eyes were 38.6 +/- 5.4 months, DLT (n = 22; range, 1 to 68 months) and 35.5 +/- 4.8 months, ALT (n = 28; range, 1 to 66 months). Those in the diode laser group (n = 16) who had more than 1 year of follow-up were tracked for 49.4 months, and those in the argon laser group (n = 21) were tracked for 45.8 months. There were no significant differences in the mean pretreatment intraocular pressures (IOPs): 21.2 mm Hg, DLT (n = 22) and 21.5, ALT 21.5 mm Hg (n = 28); P = .81] or in mean final IOPs (15.7 mm Hg, DLT and 17.1 mm Hg, ALT; P = .19). Time to surgical failure showed no significant differences, with 50% of the DLT eyes and 58% of the ALT eyes surviving at 5 years (P = .59). CONCLUSION: In eyes with open-angle glaucoma and unsatisfactory IOP control on maximally tolerated medical therapy, DLT and ALT are equally effective in lowering IOP over a 5-year period.

Microbiologic evaluation of a hydrogen peroxide sterilization system.

The reliability of chemical sterilizers (acetone and/or 30-percent hydrogen peroxide at 25 degrees C and at 60 degrees C) was tested against Bacillus subtilis inoculated onto glass slides, commercial biological indicator discs (Bacillus stearothermophilus and B. subtilis), and B. subtilis spore survival. Acetone alone was not sporicidal. Hydrogen-peroxide-sterilized glass slides were sterile after 5 minutes. The indicator discs required 25 minutes at 25 degrees C, and less than 3 minutes at 60 degrees C (P < .0001). The D value of B. subtilis in 27-percent hydrogen peroxide at 25 degrees C is 2 minutes, with z values of 22 degrees C and 26 degrees C at 25 degrees C and 40 degrees C, respectively. For delicate instruments, a 30-percent peroxide solution followed by an acetone rinse provides an effective alternative to classic heat sterilization.