The Release of Cytochrome c from Mitochondria during Apoptosis of NGF-deprived Sympathetic Neurons Is a Reversible Event

During apoptosis induced by various stimuli, cytochrome c is released from mitochondria into the cytosol where it participates in caspase activation. This process has been proposed to be an irreversible consequence of mitochondrial permeability transition pore opening, which leads to mitochondrial swelling and rupture of the outer mitochondrial membrane. Here we present data demonstrating that NGF-deprived sympathetic neurons protected from apoptosis by caspase inhibitors possess mitochondria which, though depleted of cytochrome c and reduced in size, remained structurally intact as viewed by electron microscopy. After re-exposure of neurons to NGF, mitochondria recovered their normal size and their cytochrome c content, by a process requiring de novo protein synthesis. Altogether, these data suggest that depletion of cytochrome c from mitochondria is a controlled process compatible with function recovery. The ability of sympathetic neurons to recover fully from trophic factor deprivation provided irreversible caspase inhibitors have been present during the insult period, has therapeutical implications for a number of acute neuropathologies

Bitter orange (Citrus aurantium L.) extract subchronic 90-day safety study in rats

Bitter orange (Citrus aurantium L.) extracts are widely used in dietary supplements and bitter oranges are used in various juices and food products. p-Synephrine, the primary active constituent, comprises approximately 90% of total protoalkaloids. This study, performed per OECD 408 guidance, examined the 90-day subchronic safety/toxicity of an extract standardized to 50% p-synephrine at doses of 100, 300 and 1000 mg/kg/day to male and female rats. No adverse effects were observed with respect to any of the observed parameters of clinical signs, functional observations of sensory reactivity, grip strength and motor activity, ophthalmology, body weights, hematology, food consumption, urinalysis, organ weights, as well as gross and microscopic pathology at termination at any of the doses in either sex. Treatment at 1000 mg/kg body weight/day of the extract resulted in non-adverse effects including fully reversible signs of repetitive head burrowing in the bedding material and piloerection for short periods of time in both sexes immediately after administration, which gradually disappeared by treatment day-81. A slight and reversible elevation of BUN and urea levels in male rats, and slight to mild increase in the relative but not absolute heart weights of male and female rats was observed. Based on these results, the no-observed-effect-level (NOEL) for this bitter orange extract standardized to 50% p-synephrine was 300 mg/kg, while the no-observed-adverse-effect-level (NOAEL) was 1000 mg/kg. The results indicate a high degree of safety for this bitter orange extract. Keywords: Citrus aurantium, Bitter orange, p-Synephrine, Subchronic toxicity, No-observed-adverse-effect-level (NOAEL), No-observed-effect-level (NOEL

Case Report - Greither's disease

A 14-year-old girl with diffuse palmoplantar keratoderma with hyperhidrosis and progressive extension of keratoderma to the dorsum of the hands and feet is reported. The inheritance pattern was autosomal dominant

Suppression of thermo-acoustic instabilities in horizontal Rijke tube using pulsating radial jets

Thermo-acoustic instability has been observed in gas turbines, rocket engines, and aero-engines. Acoustic perturbations grow and change the characteristics of the flow due to instability. The present work describes the use of pulsating air jets to suppress the thermo-acoustic instabilities. In present study pulsatile micro-jets are placed downstream of the burner radially which breaks the coupling between acoustic waves and unsteady heat release.A microphone connected to LIFA (LabVIEW Interface for Arduino) was used to detect the sound pressure levels. By controlling the airflow rate of the pulsatile jets, the sound pressure levels were suppressed down to the background noise level using minimum energy and time. A closed-loop control system is developed for this purpose, which works on the feedback signal acquired from microphone. To simulate the one dimensional combustion phenomenon, an experimental setup called Rijke tube was used. The suppression was most effective for the pulsatile jets of 27-33 Hz pulsation frequency range and at a flow rate of 6.8 LPM. This control strategy effectively controlled the combustion instability of around 35-42 dB. • The closed loop control method is built on DAQ and Arduino using the LabVIEW interface for Arduino (LIFA). • Developed closed loop active control method was observed to be effective for suppression of thermo-acoustic instability. • Optimum position of the radial planes of micro-jets with respect to the burner was decided to improve the efficacy of the pulsatile jets towards suppression of thermo-acoustic instability

A comparison of patient and tumour characteristics in two UK bladder cancer cohorts separated by 20 years.

Objectives To compare patient and tumour characteristics at presentation from two large bladder cancer cohorts, with recruitment separated by 15-20 years To identify significant differences in the West Midlands' urothelial cancer of the bladder (UCB) population during this period. Patients and Methods Data were collected prospectively from 1478 patients newly diagnosed with UCB in the West Midlands from January 1991 to June 1992 (Cohort 1), and from 1168 patients newly diagnosed with UBC within the same region from December 2005 to April 2011 (Cohort 2). Gender, age, smoking history, and tumour grade, stage, type, multiplicity and size at presentation were compared using a Pearson chi-square test or Cochran-Armitage trend test, as appropriate. Result Cohort 2 had a higher proportion of male patients (P = 0.021), elderly patients (P <0.001), grade 3 tumours (P <0.001), Ta/T1 tumours (P = 0.008), multiple tumours (P <0.001), and tumours of 2cm in diameter (P <0.001). Conclusions There were significant differences between the cohorts. These differences are potentially explained by an ageing population, changes in grading practices, improved awareness of important symptoms, improved cystoscopic technology, and reductions in treatment delays. Regional cohorts remain important for identifying changes in tumour and patient characteristics that may influence disease management in the UK and beyond