Importance of monovalent ions for the fast axonal transport of proteins

Proteins labeled with [35S]methionine or [3H]leucine were generated in vitro in bullfrog dorsal root ganglia and their fast axonal transport in the spinal nerves was followed during a subsequent incubation period. Incubation of the ganglia in a medium where sucrose, choline chloride, or sodium isethionate replaced NaCl caused respectively an 88, a 37, or a 76% reduction in the quantity of proteins carried by the fast axonal transport system; no decrease in synthesis of labeled proteins was observed and protein transport followed the usual time course. Incubation of desheathed spinal nerves in a medium where sucrose replaced NaCl reduced by 67% the quantity of labeled proteins which were transported past the desheathed region. Although both the axons and the dorsal root ganglia exhibit the requirement for monovalent ions to maintain fast axonal transport, the possibility that the ionic requirements of the ganglia pertain to the somal portion of the nerve cell is discussed.     

Inhibition of fast axonal transport in bullfrog nerves by dibenzazepine and dibenzocycloheptadiene calmodulin inhibitors

The effects of the calmodulin inhibitors amitriptyline, desipramine, imipramine, and clomipramine on fast axonal transport, oxidative metabolism, and density of axonal microtubules were measured in bullfrog spinal nerves in vitro. The four drugs tested inhibited the fast orthograde transport of [3H]leucine-labelled proteins and the fast retrograde transport of acetylcholinesterase at a concentration of 0.2 mM. Amitriptyline, desipramine, and imipramine were equipotent inhibitors of transport, and clomipramine was a more potent inhibitor than imipramine. The adenosine triphosphate content of the nerves was reduced by at most 19% by the compounds under study; such a reduction cannot account for the inhibition of fast axonal transport. Desipramine and imipramine had no significant effect on the density of microtubules in unmyelinated axons, whereas amitriptyline only reduced it by 18%; the inhibition of axonal transport by these three drugs can therefore not be explained by microtubule disruption. Clomipramine reduced microtubular density by 40%, and this effect may have contributed to the inhibition of fast axonal transport. The inhibition of fast axonal transport by desipramine, imipramine, and amitriptyline may be related to the inhibition of calmodulin function by these drugs. The similar potency of these three drugs as inhibitors of fast axonal transport goes in parallel with their known similar potency as calmodulin antagonists.     

A feasibility study of a telephone-supported self-care intervention for depression among adults with a comorbid chronic physical illness in primary care

Objective We assessed the feasibility and acceptability to patients of a telephone-supported self-care intervention for depression among adults aged 40 years or over with one of six targeted chronic physical illnesses and comorbid depressive symptoms in family practice settings.Methods An open, uncontrolled trial (feasibility study) was conducted among patients treated in Montreal family practices. Eligible patients were aged 40 years or over, had one or more of the targeted chronic physical illnesses for at least 6 months (arthritis, hypertension, diabetes, heart disease, asthma and chronic obstructive pulmonary disease) and were evaluated as having at least mild depressive symptoms (a score of ≥ 5 on the 9-item Patient Health Questionnaire, PHQ-9). Participants received a package of six self-care tools (information booklet, video, Internet programme, action plan, workbook and mood-monitoring tool) with telephone support by a lay coach for up to 6 months.Results In total, 63 eligible patients provided written consent and completed the baseline interview; 57 (90%) and 55 (87%) patients completed 2-month and 6-month follow-up interviews, respectively. The mean number of telephone calls made by coaches to participants was 10.5 (SD 4.0), and the average length of these calls was 10.6 minutes. At the 6-month follow-up, 83.6% of the participants reported that one or more of the tools were helpful. Clinically significant improvements were seen in depressive symptoms (as assessed by the PHQ-9) at 6 months, with an effect size of 0.88 (95% CI, 0.55, 1.14).Conclusion A telephone-supported self-care intervention for depression was feasible, was acceptable to patients, and was associated with a significant 6-month improvement in depressive symptoms. A randomised trial of this intervention is justified.     

Substrate specificity of the placental microsomal aromatase

Using an accurate and sensitive assay for the human placental aromatase we have found apparent Km values for androstenedione (4-androstene-3,17-dione) and testosterone to be 14 ± 4.0 nM and 41 ± 12 nM respectively. These values were significantly different (p < 0.001). Analyses at substrate concentrations 5–10 fold above and below the Km values did not indicate any anomalous kinetic behavior. Mixed substrate experiments were consistent with a single enzyme metabolizing both steroids: each competitively inhibited the aromatization of the other, and the “Ki” values were the same as their apparent Km values. Sodium chloride (1.2M) significantly increased the rate of testosterone aromatization by decreasing its Km value and had no significant effect on the aromatization of androstenedione. However, in the presence of this salt testosterone still inhibited the aromatization of androstenedione competitively with a “Ki” equal to its apparent Km. Our data is therefore consistent with the proposal that human placental microsomes contain a single “high affinity” site for the aromatization of androstenedione and testosterone.     

Effect of time-varying load on degree of bronchoconstriction in the dog

It is wellestablished that the degree of airway smooth muscle shortening producedby a given dose of bronchial agonist is greatly affected by lungvolume. The airways are tethered by parenchymal attachments, thetension of which increases progressively with lung volume, therebypresenting a commensurately increasing hindrance to smooth musclecontraction. Earlier studies (P. F. Dillon, M. O. Aksoy, S. P. Driska,and R. A. Murphy. Science 211:495-497, 1981) presented evidence that smooth muscle contractioninitially involves rapidly cycling cross bridges, whichthen change to noncycling (latch) bridges. They also suggested thatmost of the muscle shortening occurs during the early rapidcross-bridge phase. This implies that smooth muscle subject to a givenload early in contraction should shorten less than when it is subjectto the same load later on. An in vitro study (W. Li and N. L. Stephens.Can. J. Physiol. Pharmacol. 72:1458-1463, 1994) obtained support for this notion. To test thishypothesis in vivo, we measured the changes in lung impedance at 1 and6 Hz produced in dogs by a bolus intravenous injection of methacholinewhen lung volume was increased for 10 s at different times afterinjection. We found that the changes in mechanics were greatlyinhibited, whereas lung volume was elevated. However, when lung volumewas returned to its initial level, the lung mechanics continued tochange at a rate unaffected by the preceding volume change. We concludethat temporary mechanical inhibition of airway smooth muscle shorteningin the normal dog in vivo merely delays an otherwise normal course ofcontraction.

     

Energy cost of front-crawl swimming in women

The purpose of this study was to examine the relationship between the energy cost of swimming per unit distance (Cs) at different velocities (v) and performance level, body size and swimming technique in women. A total of 58 females swimmers were studied. Three performance levels (A, B, C) were determined, ranging from the slower (A) to the faster (B, C). At level C and at 1.1 m.s-1, Cs,1.1 was reduced by 7% when directly compared to level B. The Cs,1.1 was reduced by 10% when calculated per unit of height (h) and by 37% when calculated per unit of h and hydrostatic lift (HL). For the whole group of swimmers, the equation regression was Cs,1.1 = 0.27 h-2.38 HL - 7.5 (r = 0.53, P less than 0.01). To evaluate the specific influence of arm length two groups of long- and short-armed swimmers were selected among swimmers of similar h and performance. The Cs was significantly higher (P less than 0.05) by 12%, SD 2.2%, for short-armed than for long-armed swimmers. To evaluate the influence of different types of swimming technique, two other groups of similar performance and anthropometric characteristics were selected. The Cs was significantly higher (P less than 0.05) by 12%, SD 4.5% for swimmers using for preference their legs rather than their arms. The Cs of the sprinters was 15.7%, SD 2% higher than that of the long-distance swimmers. For all groups, Cs increased with v on average by 8% to 11% every 0.1 m.s-1. These findings showed that Cs variations of these women were close to those previously demonstrated for men. The Cs depends on performance level, body size, buoyancy, swimming technique and v.