NMR Microscopy of Single Neurons Using Spin Echo and Line Narrowed 2DFT Imaging

NMR microimages of single neural cells were acquired at 500 MHz using a conventional spin echo pulse sequence and a line-narrowing sequence that eliminates susceptibility effects. The data show that any contribution to the measured T₂ relaxation rate arising from diffusion in local field inhomogeneities using spin echo sequences at high fields and high spatial resolution is relatively small. We conclude that the measured T₂ difference between the nucleus and cytoplasm in these cells represents primarily a true T₂ relaxation effect arising from the interactions of water with macromolecules in the two compartments and does not result from microsusceptibility differences. These observations have implications regarding water compartmentation in single cells and the interpretation of the MR characteristics of tissues in vivo.     

Balance and recovery from a perturbation are impaired in people with functional ankle instability.

OBJECTIVE: To determine if differences in balance and recovery would be found between controls and participants with unilateral or bilateral functional ankle instability (FAI). DESIGN: Cross-Sectional Study. SETTING: University laboratory and Community premises. PARTICIPANTS: Twenty healthy participants(C), 19 participants with unilateral FAI [both the uninjured (UC) and unstable ankle (UI) were included] and 22 participants with bilateral FAI (BI). MAIN OUTCOME MEASURES: Balance was measured in single leg stance as: number of part foot lifts in 30 s; magnitude of medio-lateral ankle movement in two foot positions; and ability to balance on the ball of the foot. Recovery was determined by time to return to baseline medio-lateral ankle movement after a 15 degree inversion perturbation. RESULTS: The controls lifted the foot fewer times than the other three groups [C = 12.7 +/- 1.8 (mean +/- SE) foot lifts, UC = 22.9 +/- 2.5, UI = 25.1 +/- 2.3, and BI = 21.1 +/- 2.2, t-test, P = 0.006] and recovered significantly faster than the unstable ankles [C = 1.53 +/- 0.42 sec (median +/- SE), UI = 2.34 +/- 0.30 sec, BI = 2.15 +/- 0.70 sec, P < 0.02]. With FAI measured by the Cumberland Ankle Instability Tool, the external control group balanced on demi-pointe better than both instability groups (P < 0.05), and recovered quicker than all groups. CONCLUSION: There are differences in balance and recovery between external controls and participants with both unilateral and bilateral FAI but not between the legs of participants with unilateral FAI.     

Positive affect predicts improved lip movement in facial movement disorder.

OBJECTIVES: Positive affect in individuals with a facial movement disorder may promote lip corner movement (zygomaticus major) during smiling. We investigated whether a positive affect marker (orbicularis oculi activity) observed in an initial clinic visit of individuals with facial movement disorder (N = 28) predicted increased lip corner movement at a subsequent visit. STUDY DESIGN AND SETTING: In this clinical outcomes study, lip corner movement was assessed with the use of automated facial analysis. Asymmetry of movement was compared in individuals who smiled with or without the positive affect marker at an initial clinic visit. RESULTS: The positive affect marker at the initial visit was associated with a reduction in the asymmetry of the lip corner movement at the second visit. CONCLUSION: Positive affect predicts improved facial movement outcomes in patients with facial movement disorders. SIGNIFICANCE: Positive emotion in facial movement patients may be an important factor in recovery of facial movement during therapy.     

The effect of combinations of qinghaosu (artemisinin) with standard antimalarial drugs in the suppressive treatment of malaria in mice

Artemisinin is a novel antimalarial drug isolated in China from the wormwood plant Artemisia annua L. Studies with rodent malaria were carried out to detect antagonism and synergism with a variety of antimalarial drugs. Isobolograms of drug interaction were plotted at the ED90 level. With a normally susceptible strain of Plasmodium berghei, marked potentiative synergism was found with mefloquine, tetracycline and spiramycin. There was some synergism also with primaquine. Combinations of artemisinin with dapsone, sulfadiazine, sulfadoxine, pyrimethamine, pyrimethamine/sulfadoxine and cycloguanil showed antagonism. A high degree of potentiation was shown between artemisinin and primaquine with a primaquine-resistant strain, whilst the combination with mefloquine showed enhanced potentiation with a mefloquine-resistant strain. Combinations of artemisinin with mefloquine, primaquine, tetracycline or clindamycin showed marked potentiation with an artemisinin-resistant strain. The mechanisms underlying the drug interactions observed are discussed.     

Ethics of asking trauma-related questions and exposing participants to arousal-inducing stimuli.

This study examined ethical concerns related to exposing participants with childhood victimization histories to both trauma-specific and non-trauma-specific stimuli. We asked participants questions about childhood victimization experiences and exposed participants to a negatively-arousing experimental condition. Following each of these procedures and at a one-week follow-up session, participants completed a measure designed to asses their reactions to participation. The measure included several questions to assess reactions including questions about distress, benefit, and willingness to participate in the study again. Overall, participants reported low levels of distress and described their participation experience as interesting, enjoyable, and somewhat beneficial. Participants also indicated that they would be willing to participate in the study again with the knowledge of what participation was actually like. Participants with childhood trauma histories and PTSD symptoms reported more distress during the childhood maltreatment screening compared to other participants. However, the level of distress they experienced was mild and transitory. Our findings add to the emerging data indicating that individuals find their participation in trauma-related research to be a positive experience overall, rather than a harmful one.     

Effects of cholinergic modulation on serum insulin-like growth factor4 and its binding proteins in normal and diabetic subjects*

OBJECTIVE We wished to study alterations In serum Insulin-like growth factor-I (IGF-I) and its binding proteins in subjects with insulin dependent diabetes mellitus (IDDM) and possible relations with metabolic and GH secretory status, before and after cholinergic modulation. In addition, we have Investigated whether cholinergic modulation exerts any effects on IGF-I secretion, Independently of any actions on GH secretory status. DESIGN All subjects received OH releasing hormone (GHRH) 1-44; 80 μg i.v.) alone and 60 minutes following 120mg of pyridostigmine orally or 200 mg of plrenzepine orally. The three tests were carried out In random order at least one week apart. Blood was sampled at 15-mInute Intervals over 120 minutes. PATIENTS Twelve male subjects with IDDM and no clinical evidence of complications were selected on the basis of HbA₁ levels to provide a wide range of metabolic control. SIX normal male subjects were also studied. MEASUREMENTS Serum IGF-I, IGF-binding protein 1 (IGFBP-1) and IGFBP-3 were measured at regular intervals throughout the study. Fasting plasma glucose and HbA₁ were measured before each study to provide measures of metabolic control. RESULTS Serum IGF-I and IGFBP-3 levels were significantly lower while serum IGFBP-I levels were significantly higher In the diabetic subjects. Plrenzepine had no effect on serum IGF-I, IGFBP-1 or IGFBP-3 In diabetic subjects but caused a significant Increase In serum IGF-I and IGFBP-3 levels in normal subjects. Pyridostigmine had no effect on IGF-I, IGFBP-1 or IGFBP-3 In either diabetic or normal subjects. IGFBP-1 levels were significantly correlated with fasting plasma glucose but no correlation was demonstrated between measures of diabetic control and serum IGF-I or IGFBP-3 levels In diabetic subjects, nor was there any correlation between OH responses to GHRH alone or after plrenzepine or pyridostigmine pretreatment and serum levels of IGF-I, IGFBP-1 or IGFBP-3. CONCLUSION These data confirm that subjects with IDDM have reduced serum IGF-I and IGFBP-3 and Increased IGFBP-1 levels, the latter being directly related to the fasting plasma glucose concentrations. The absence of any relation between changes In the IGF-I system and altered GH neuroregulation after cholinergic modulation suggests that changes In IGF-I are not the sole contributors to the altered GH neuroregulation which occurs In IDDM. We have also shown an acute stimulatory effect of pirenzepine on serum IGF-I and IGFBP-3 In normal subjects which Is not present in IDDM although the underlying mechanism Is unknown.