Mitochondrial Dysfunction Is the Focus of Quaternary Ammonium Surfactant Toxicity to Mammalian Epithelial Cells

Surfactants have long been known to have microbicidal action and have been extensively used as antiseptics and disinfectants for a variety of general hygiene and clinical purposes. Among surfactants, quaternary ammonium compounds (QAC) are known to be the most useful antiseptics and disinfectants. However, our previous toxicological studies showed that QAC are also the most toxic surfactants for mammalian cells. An understanding of the mechanisms that underlie QAC toxicity is a crucial first step in their rational use and in the design and development of more effective and safer molecules. We show that QAC-induced toxicity is mediated primarily through mitochondrial dysfunction in mammalian columnar epithelial cell cultures in vitro. Toxic effects begin at sublethal concentrations and are characterized by mitochondrial fragmentation accompanied by decreased cellular energy charge. At very low concentrations, several QAC act on mitochondrial bioenergetics through a common mechanism of action, primarily by inhibiting mitochondrial respiration initiated at complex I and, to a lesser extent, by slowing down coupled ADP phosphorylation. The result is a reduction of cellular energy charge which, when reduced below 50% of its original value, induces apoptosis. The lethal effects are shown to be primarily a result of this process. At higher doses (closer to the critical micellar concentration), QAC induce the complete breakdown of cellular energy charge and necrotic cell death.     

Molecular characterization,serotyping, and antibiotic susceptibility profile of Leptospira interrogans serovar Copenhageni isolates from Brazil

Leptospira interrogans serogroup Icterohaemorrhagiae is the major serogroup infecting humans worldwide, and rodents and dogs are the most significant transmission sources in urban environments. Knowledge of the prevalent serovars and their maintenance hosts is essential to understand the epidemiology of leptospirosis. In this study, 20 Leptospira isolates were evaluated by pulsed-field gel electrophoresis (PFGE), variable number tandem-repeat analysis (VNTR), serotyping, and determination of antimicrobial resistance profile. Isolates, originated from bovine, canine, human, and rodent sources, were characterized by microscopic agglutination test with polyclonal and monoclonal antibodies and were identified as L. interrogans serogroup Icterohaemorrhagiae serovar Copenhageni. MICs of antimicrobials often used in veterinary medicine were determined by broth microdilution test. Most of tested antibiotics were effective against isolates, including penicillin, ampicillin, and ceftiofur. Higher MIC variability was observed for fluoroquinolones and neomycin; all isolates were resistant to trimethoprim/sulfamethoxazole and sulphadimethoxine. Isolates were genotyped by PFGE and VNTR; both techniques were unable to discriminate between serovars Copenhageni and Icterohaemorrhagiae, as expected. PFGE clustered all isolates in 1 pulsotype, indicating that these serovars can be transmitted between species and that bovine, rodent, and dogs can maintain them in the environment endangering the human population.     

The curriculum indexing database for stanford university school of medicine

The Curriculum Indexing Database (CID) was created to index the content of preclin‐ical courses on a session‐by‐session basis using a controlled vocabulary. A commercially available database software package, Filemaker Pro, allows the system to be set up, maintained, and utilized by individuals with little computer expertise and at reasonable expense. The development of the database vocabulary, consisting of 382 keywords in 20 possible categories, is discussed. A large free‐text field enables more specific content identification. Keywords from one or more fields can be designated for a search. A variety of report formats are available and custom reports can be created. CID provides an accurate curriculum inventory that has been useful in reducing redundancy and avoiding omissions, reviewing sequencing of material, planning vertical integration of special topics, and providing background information for the development or restructuring of courses. We are currently adding the required clinical curriculum to CID.     

Nitric oxide synthase in retina and optic nerve head of rat with increased intraocular pressure and effect of timolol

We investigated the expression of nitric oxide synthase (NOS) isoforms -1, -2 and -3 in the retina and optic nerve head (ONH) in an experimental rat model of elevated intraocular pressure (IOP) before and after treatment with timolol, to assess whether its neuroprotective action is associated with the activity of these enzymes. Episcleral vein cauterization in unilateral eyes of Wistar rats was performed to produce elevated IOP. Histological sections of retina and ONH from animals with normal IOP, with elevated IOP, and elevated IOP treated with timolol, were studied by immunohistochemistry with antibodies to NOS-1, NOS-2, and NOS-3. In the control rats, NOS-1 was localized to photoreceptor inner segments, amacrine cells and bipolar cells in the retina, and in astrocytes, pericytes and vascular nitrergic terminals in the ONH. NOS-3 immunostaining localized to the endothelial cells. The rats with elevated IOP showed increased expression of NOS-1 in the plexiform layers of the retina and reactive astrocytes in the ONH. These cells also showed NOS-2 positivity. The rats treated with timolol showed reduced expression of NOS-1 in the retina and ONH. NOS-2 was only detected in a few groups of astrocytes in the ONH. NOS-3 was unchanged in both elevated IOP and timolol-treated groups. These results show that excessive levels of NO synthesized by the NOS-1 and -2 isoforms, considered neurotoxic, might contribute to the progressive lesions of retinal ganglion cell axons. Their reduction after treatment suggests a possible neuroprotective effect of timolol in neurons exposed to excessive amounts of NO.     

Kidney transplantation and waiting list for renal transplantation for human immunodeficiency virus patients

Introduction

The aim of this study was to evaluate the experience of a renal transplantation unit in the management of human immunodeficiency virus (HIV)-infected patients with end-stage renal disease (ESRD).

Methods

A prospective study was performed between 2005 and 2010 among 23 patients with ESRD.

Results

In this study 83% of HIV- infected patients with ESRD were included on the waiting list for renal transplantation with 4 patients in a clinical evaluation phase. During the follow-up, 52% of waiting list patients (n = 11) received a renal transplant, and 1 patient underwent a simultaneous kidney-pancreas transplantation. Among the waiting list group we observed a significant later exclusion (43%; n = 3). Among the transplanted group there was a high but clinically inconsequential prevalence of acute tubular necrosis (36%; n = 4) and acute rejection episodes (36%; n = 4). The renal function showed a serum creatinine of 1.1 mg/dL at a follow-up of 24 + 12 months. All patients on the waiting list and after the transplantation are prescribed combined antiretroviral treatment (cART) with a low viral load <50 with CD4 >200.

Conclusions

HIV-infected patients with ESRD should be considered to be candidates for renal transplantation if they meet the HIV inclusion criteria. Renal transplantation in adequately selected HIV-infected patients is a safe procedure with acceptable patient and graft survivals.     

CT evaluation of gastric wall pathology

The purpose of this study is to show the CT features of common and infrequent pathological lesions of the gastric wall. Although CT features are not often specific, familiarity with the most frequent pathological gastric findings on CT can assist in differential diagnosis.     

Physical fitness effect on bone mass is mediated by the independent association between lean mass and bone mass through adolescence: a cross-sectional study

We studied 278 adolescents (169 females) aged 13.0–18.5 years to elucidate whether an independent effect of physical fitness and lean mass in the differences between male and female bones can be detected. Lean and fat masses and bone mineral content (BMC) were measured with DXA. Physical fitness was evaluated with six different tests included in the EUROFIT test battery (flexibility, isometric, dynamic and endurance strength, speed, and cardiovascular fitness). To test the independent relationship between physical fitness and bone mass, multiple regression analysis was applied, including lean mass, age, and Tanner development as covariates. The males had a 43% lower fat mass and 40% and 16% higher lean mass and total BMC compared with the females (all P < 0.05). After adjustment for differences in body size and lean mass, the females exhibited a 7.4% higher BMC than the males (P < 0.05). The multiple regression analysis showed that lean mass had an independent relationship with bone mass (P < 0.001), explaining 67% of the total variance in whole-body BMC. In males, change in R ² was 0.658 for hand grip and 0.035–0.151 for the rest of physical fitness-related variables; but 0.019–0.042 in females (all P–0.001); however, the independent relationships between physical fitness and bone disappeared after controlling for lean mass. In conclusion, it is likely the differences between male and female in bone mass could be explained by differences in lean mass and physical fitness.     

Negative pressure wound therapy reduces incidence of postoperative wound infection and dehiscence after long-segment thoracolumbar spinal fusion: a single institutional experience

Background contextWound dehiscence and surgical site infections (SSIs) can have a profound impact on patients as they often require hospital readmission, additional surgical interventions, lengthy intravenous antibiotic administration, and delayed rehabilitation. Negative pressure wound therapy (NPWT) exposes the wound site to negative pressure, resulting in the improvement of blood supply, removal of excess fluid, and stimulation of cellular proliferation of granulation tissue.PurposeTo assess the incidence of wound infection and dehiscence in patients undergoing long-segment thoracolumbar fusion before and after the routine use of NPWT.Study designRetrospective study.Patient sampleOne hundred sixty patients undergoing long-segment thoracolumbar spine fusions were included in this study.Outcome measuresPostoperative incidence of wound infection and dehiscence.MethodsAll adult patients undergoing thoracolumbar fusion for spinal deformity over a 6-year period at Duke University Medical Center by the senior author (CB) were included in this study. In 2012, a categorical change was made by the senior author (CB) that included the postoperative routine use of incisional NPWT devices after primary wound closure in all long-segment spine fusions. Before 2012, NPWT was not used. After primary wound closure, a negative pressure device is contoured to the size of the incision and placed over the incision site for 3 postoperative days. We retrospectively review the first 46 cases in which NPWT was used and compared them with the immediately preceding 114 cases to assess the incidence of wound infection and dehiscence.ResultsOne hundred sixty (NPWT: 46 cases, non-NPWT: 114 cases) long-segment thoracolumbar spine fusions were performed for deformity correction. Baseline characteristics were similar between both cohorts. Compared with the non-NPWT cohort, a 50% decrease in the incidence of wound dehiscence was observed in the NPWT patient cohort (6.38% vs. 12.28%, p=.02). Similarly, compared with the non-NPWT cohort, the incidence of postoperative SSIs was significantly decreased in the NPWT cohort (10.63% vs. 14.91%, p=.04).ConclusionsRoutine use of incisional NPWT was associated with a significant reduction in the incidence of postoperative wound infection and dehiscence.