Influence of lecithin on mitochondrial DNA and age-related hearing loss.

OBJECTIVES: Lecithin is a polyunsaturated phosphatidylcholine (PPC), which are high energy functional and structural elements of all biologic membranes. PPC play a rate-limiting role in the activation of numerous membrane-located enzymes, including superoxide dismutase and glutathione, which are important antioxidants protecting cell membranes from damage by reactive oxygen species (ROS). ROS-induced damage to mitochondrial DNA may lead to reduced mitochondrial function in the cochlea and resultant hearing loss. STUDY DESIGN AND SETTING: The effects of lecithin on aging and age-associated hearing loss were studied in rats by measuring hearing sensitivities using auditory brainstem responses (ABR). In addition, mitochondrial function as a measure of aging was assessed by determining mitochondrial membrane potentials using flow cytometry and by amplifying mitochondrial DNA deletions associated with aging. Harlan-Fischer rats aged 18 to 20 months (n = 14) were divided into 2 groups. The experimental group was supplemented orally for 6 months with lecithin, a purified extract of soybean phospholipid (Nutritional Therapeutics, Allendale, NJ). RESULTS: The data obtained were compared with the control group. ABRs were recorded at 2-month intervals and showed significant preservation of hearing sensitivities in the treated subjects. Flow cytometry revealed significantly higher mitochondrial membrane potentials in the treated subjects, suggesting preserved mitochondrial function. Finally, the common aging mitochondrial DNA deletion (mtDNA(4834)) were amplified from brain and cochlear tissue including stria vascularis and auditory nerve. This specific deletion was found significantly less frequent in all tissues in the treated group compared with the controls. CONCLUSION: These experiments support our hypothesis and provide evidence that lecithin may preserve cochlear mitochondrial function and protect hearing loss associated with aging.     

Establishing generic remediation goals for the polycyclic aromatic hydrocarbons: critical issues.

Polycyclic aromatic hydrocarbons (PAHs) were one of the first classes of compounds identified as carcinogens and are often chemicals of concern at hazardous waste sites. Remediation goals established by regulatory agencies for carcinogenic PAHs in soil are generally either risk based or based on the method detection limits. PAHs are products of incomplete combustion, are components of petroleum, and as such, are prevalent in the environment from both natural and anthropogenic sources. Background concentrations are often above risk- or detection limit-based criteria, and therefore these remediation goals are of limited practical use as target criteria. In addition, the approaches used to establish target criteria do not account for several factors that may produce over- or underestimates of risk associated with the PAHs. Because of the frequency with which these compounds are detected, it is imperative that reasonably achievable and practical remediation goals be established. This paper examines the various factors that contribute to over- and underestimates of risks associated with PAHs and presents an approach for establishing cleanup criteria that takes into account health risks, background concentrations, and achievability.     

The anterior inferior cerebellar arterial network supplying the rat cochlea and its role in autoregulation of cochlear blood flow

Summary The sensitivity of the cochlea is dependent upon maintenance of a delicate homeostatic environment. One mechanism which participates in providing this environment is the autoregulation of cochlear blood flow. This autoregulation is ensured through the interaction of sympathetic, peptidergic and hemodynamic mechanisms. The current study demonstrates an adaptation that also participates in cochlear blood flow autoregulation. Specifically, an anterior inferior cerebellar arterial network is described and the relative contributions of each of its vessels to total cochlear blood flow is measured using laser Doppler flowmetry. The results show that each collateral vessel contributes to the blood supply of the cochlea and that reperfusion is accompanied by hyperemia. These findings suggest an adaptation that provides stable blood flow through redundancy and compensatory potential. Additionally, these observations have implications for experimental models of ischemia.     

CORRELATION OF IMMUNOLOGICAL SURFACE ANTIGENS WITH SURVIVAL IN DIFFUSE LARGE CELL LYMPHOMA

The prognostic value of immunophenotyping lymphomas with a panel of monoclonal antibodies (Mab) to various lymphoid antigens was assessed by studying 47 cases of diffuse large cell lymphoma. Cell suspensions were analysed by flow cytometry after labelling by indirect immunofluorescence. Thirty-eight cases were demonstrated to be of B cell and nine of T cell phenotype. Univariate analysis demonstrated that survival was significantly longer in patients expressing higher levels of HLA-DR (p=0·01) and normal levels of CD8 (p=0·04) but was not significantly associated with any of the other antigens. Our results support the possible value of HLA-DR in determining the prognosis of patients with diffuse large cell lymphoma.     

Synthesis of Diene‐Functionalized Macromonomers via Functionalization with Hexa‐1,3,5‐triene

The reaction of poly(styryl)lithium (PSLi) with hexa‐1,3,5‐triene (HXT) was studied as a route to diene‐functionalized macromonomers. When PSLi was reacted with 1.5 molar equivalents of HXT for 2.5 h at ?10 °C in toluene, it was found that the diene‐functionalized macromonomer was obtained in high yield; however, oligomerization of the HXT was observed by matrix‐assisted laser absorption ionization time‐of‐flight mass spectrometry (MALDI‐TOF MS). Oligomerization was eliminated by running the reaction with only 1.2 molar equivalents of HXT to PSLi and allowing the reaction to run for 15 min at ?10 °C in toluene. The resulting polymer exhibited high diene chain‐end functionality and no oligomerization was observed by MALDI‐TOF MS. ¹³C NMR spectroscopy and the attached‐proton test (APT), along with calculated chemical shifts, showed the presence of both the 1,2‐ and 1,4‐addition chain‐end structures. Further analysis by the reaction of the functional polymer with maleic anhydride indicated that 18 wt.‐% of the product was unreactive, either because of a 1,4‐addition chain‐end structure or a nonfunctional polymer. The structure of the maleic anhydride‐modified polymer was determined by MALDI‐TOF MS and ¹³C NMR spectroscopy. Preliminary work on the reactivity of the diene‐functionalized macromonomers was performed by the addition of a large excess of PSLi to a solution of macromonomer followed by characterization by size‐exclusion chromatography (SEC).

The formation of hexa‐1,3,5‐triene‐functionalized polystyrenes and their reaction with maleic anhydride.     

Multiple frequency bioelectrical impedance for the prediction of total body potassium in cystic fibrosis

The use of multiple frequency bioelectrical impedance analysis (MFBIA) was compared with single frequency bioelectrical impedance analysis (SFBIA) and anthropometry to estimate the size of the body cell mass (BCM) in a paediatric cystic fibrosis population. BCM was independently determined from the accepted gold standard reference of total body potassium (TBK). MFBIA was used to measure the impedance of the body at 248 frequencies from 4 kHz to 1 MHz. Data were analysed using Cole-Cole plots of reactance versus resistance. The limits of agreement procedure was used to determine the reliability and precision of the different techniques to predict values for TBK, in an individual subject. The results indicate that MFBIA with a precision of 12% offers little improvement over single frequency BIA but is better and more accurate than anthropometry for the prediction of TBK in an individual patient.     

Interaction between spike waveform classification and temporal sequence detection

In vivo extracellular recordings have allowed researchers to study the response properties of neurons to behaviorally relevant stimuli. In this paper we use multiple tetrode recordings from the hippocampus of the freely behaving rat to show that the action potential amplitude of a given cell can vary in a systematic and activity dependent manner over behaviorally relevant time scales. Since the discrimination algorithms used by experimenters to isolate cells from extracellular recordings are based on differences in waveforms, we show how these systematic changes in waveform shape can lead to non-random errors in single cell isolation. We further demonstrate that these non-random errors can lead to apparent temporal ordering effects between neurons in the absence of any specific temporal relationship. A firm understanding of these naturally occurring physiological changes is therefore critical for the evaluation of higher order phenomena such as the temporally correlated firing of ensembles of neurons.     

An analysis tool to investigate theft or tampering of controlled substances

The authors describe a quantitative analysis method to investigate narcotic theft or tampering on a nursing unit. It provides procedure to follow after any suspected tampering or outright theft of controlled substances. Several methods to review all current controlled substance activity for a given nursing unit and their possible relations to the loss are described. In addition several working documents are described to aid in the analysis of the loss.