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.     

Gait analysis in patients with idiopathic scoliosis

Introduction The goal of this study was to observe scoliotic subjects during level walking to identify asymmetries—which may be related to a neurological dysfunction or the spinal deformity itself—and to correlate these to the severity of the scoliotic curve.Methods We assessed the gait pattern of ten females (median age 14.4) with idiopathic scoliosis characterised by a left-lumbar and a right-thoracic curve component. Gait analysis consisted of 3D kinematic (VICON) and kinetic (Kistler force plates) measurements. The 3D-segment positions of the head, trunk and pelvis, as well as the individual joint angles of the upper and lower extremities, were computed during walking and static standing. Calculation of pertinent kinetic and kinematic parameters allowed statistical comparison.Results All subjects walked at a normal velocity (median: 1.22 m/s; range:1.08–1.30 m/s; height-adjusted velocity: 0.75 m/s; range: 0.62–0.88 m/s). The timing of the individual gait phases was normal and symmetrical for the whole group. Sagittal plane hip, knee and ankle motion followed a physiological pattern. Significant asymmetry was observed in the trunks rotational behaviour in the transverse plane. During gait, the pelvis and the head rotated symmetrically to the line of progression, whereas trunk rotation was asymmetric, with increased relative forward rotation of the right upper body in relation to the pelvis. This produced a torsional offset to the line of progression. Minimal torsion (at right heel strike) measured: median 1.0° (range: 5.1°–8.3°), and maximal torsion (at left heel strike) measured 11.4° (range 6.9°–17.9°). The magnitude of the torsional offset during gait correlated to the severity of the thoracic deformity and to the standing posture, whereas the range of the rotational movement was not affected by the severity of the deformity. The ground reaction forces revealed a significant asymmetry of [Msz], the free rotational moment around the vertical axis going through the point of equivalent force application. On the right side, the initial endo-rotational moment was lower, followed by a higher exo-rotational moment than on the left. All the other force parameters (vertical, medio–lateral, anterior–posterior), did not show a significant side difference for the whole group. The use of a brace stiffened torsional motion. However the torsional offset and the asymmetry of the free rotational moment remained unchanged.Conclusion The most significant and marked asymmetry was seen in the transverse plane, denoted as a torsional offset of the upper trunk in relation to the symmetrically rotating pelvis. This motion pattern was reflected by a ground-reaction-force asymmetry of the free rotational moment. Further studies are needed to investigate whether this behaviour is solely an expression of the structural deformity or whether it could enhance the progression of the torsional deformity.No financial assistance was provided for this work     

Comparing the short-term outcomes of totally intracorporeal gastroduodenostomy with extracorporeal gastroduodenostomy after laparoscopic distal gastrectomy for gastric cancer: a single surgeon’s experience and a rapid systematic review with meta-analysis

Background

Since delta-shaped gastroduodenostomy was introduced, many surgeons have utilized laparoscopic distal gastrectomy (LDG) with totally intracorporeal Billroth I (ICBI) for gastric cancer, because it is expected to have several advantages over laparoscopic-assisted distal gastrectomy with extracorporeal Billroth I (ECBI). In this study, we compared these two reconstruction options to evaluate their outcomes.

Methods

The data of 166 gastric cancer patients who underwent LDG performed by a single surgeon between April 2009 and February 2012 were analyzed retrospectively. The subjects were divided into ECBI (n = 106) and ICBI (n = 60) groups, and then the clinical characteristics, surgical outcomes, symptoms, and change in BMI at 3 months after surgery were compared. Furthermore, a rapid systematic review and meta-analysis were conducted.

Results

The operative time was significantly shorter in the ICBI group (197.4 ± 45.5 vs. 157.1 ± 43.9 min), but blood loss was similar between the groups. Regarding surgical outcomes, there were no significant differences in the length of hospital stay, soft diet initiation, visual analogue scale, frequency of analgesics injection, and postoperative white blood cell counts and C-reactive protein levels between the groups. The surgical complication rates were 5.7 and 13.3 % in the ECBI and ICBI groups, respectively, and one case of anastomosis leakage was observed in each group. At 3 months after surgery, reflux symptoms were more frequent in the ICBI group, but other gastrointestinal symptoms and the change of BMI were similar between the groups. The meta-analysis revealed no significant differences in the operative time, time to first flatus, length of hospital stay, frequency of analgesic usages, and rates of anastomosis complications between the groups.

Conclusions

We could not demonstrate the clinical superiority of ICBI over ECBI based on our data and a rapid systematic review and meta-analysis. The anastomosis method may be selected according to patient conditions and the surgeon’s preference.     

Contrast-enhanced power Doppler US: is it useful in the differentiation of gallbladder disease?

Thirteen patients with gallbladder disease underwent power Doppler ultrasound (PDUS) before and after microbubble contrast agent injection. Lesion and liver bed vascularity was evaluated. Pathological diagnoses in nine patients were two acute cholecystitis, four chronic inflammation, one adenoma and two adenocarcinoma. Two cases of cancer were included on clinical and radiological findings. Two cases were excluded because no pathologic diagnosis was available. Liver bed hyperemia was noted only in acute cholecystitis. Contrast-enhanced PDUS was superior to nonenhanced PDUS in the demonstration of vascularity of gallbladder diseases. However, contrast-enhanced PDUS has limited value in the differentiation.     

Intracranial and Spinal Ependymomas: Review of MR Images in 61 Patients

Objective

To compare the age distribution and characteristic MR imaging findings of ependymoma for each typical location within the neuraxis.

Materials and Methods

During a recent eleven-year period, MR images of 61 patients with histologically proven ependymomas were obtained and retrospectively reviewed in terms of incidence, peak age, location, size, signal intensity, the presence or absence of cyst and hemorrhage, enhancement pattern, and other associated findings.

Results

Among the 61 patients, tumor location was spinal in 35 (57%), infrartentorial in 19 (31%), and supratentorial in seven (12%). In four of these seven, the tumor was located in brain parenchyma, and in most cases developed between the third and fifth decade. Approximately half of the infratentorial tumors occurred during the first decade. The signal intensity of ependymomas was non-specific, regardless of their location. A cystic component was seen in 71% (5/7) of supratentorial, 74% (14/19) of infratentorial, and 14% (5/35) of spinal cord tumors. Forty-nine percent (17/35) of those in the spinal cord were associated with rostral and/or caudal reactive cysts. Intratumoral hemorrhage occurred in 57% (4/7) of supratentorial, 32% (6/19) of infratentorial, and 9% (3/35) of spinal cord tumors. In 17% (6/35) of spinal ependymomas, a curvilinear low T2 signal, suggesting marginal hemorrhage, was seen at the upper and/or lower margins of the tumors. Peritumoral edema occurred in 57% (4/7) of supratentorial, 16% (3/19) of infratentorial and 23% (8/35) of spinal cord tumors. Seventy-two percent (5/7) of supratentorial and 95% (18/19) of infratentorial tumors showed heterogeneous enhancement, while in 50% (17/34) of spinal cord tumors, enhancement was homogeneous.

Conclusion

Even though the MR imaging findings of ependymomas vary and are nonspecific, awareness of these findings, and of tumor distribution according to age, is helpful and increases the likelihood of correct preoperative clinical diagnosis.     

Identification of fluocinolone acetonide to prevent paclitaxel‐induced peripheral neuropathy

Paclitaxel (PTX) is among the most commonly used cancer drugs that cause chemotherapy‐induced peripheral neuropathy (CIPN), a debilitating and serious dose‐limiting side effect. Currently, no drugs exist to prevent CIPN, and symptomatic therapy is often ineffective. In order to identify therapeutic candidates to prevent axonal degeneration induced by PTX, we carried out a phenotypic drug screening using primary rodent dorsal root ganglion sensory neurons. We identified fluocinolone acetonide as a neuroprotective compound and verified it through secondary screens. Furthermore, we showed its efficacy in a mouse model of PTX‐induced peripheral neuropathy and confirmed with four different cancer cell lines that fluocinolone acetonide does not interfere with PTX's antitumor activity. Our study identifies fluocinolone acetonide as a potential therapy to prevent CIPN caused by PTX.