Synthesis and evaluation of chalcogenopyrylium dyes as potential sensitizers for the photodynamic therapy of cancer.

A series of thiopyrylium (2), selenopyrylium (3), and telluropyrylium dyes (4) was prepared via the addition of Grignard reagents to either 2, 6-di(4-dimethylamino)phenylchalcogenopyran-4-ones (5a) or 2-[4-(dimethylamino)phenyl]-6-phenylchalcogenopyran-4-ones (5b) followed by elimination and ion exchange to give the chloride salts. The absorption spectra and quantum yields for singlet oxygen generation of these dyes suggested that the dyes would have utility as sensitizers for PDT. Selenopyrylium dyes 3a and 3d with quantum yields for singlet oxygen generation of 0.040 and 0.045, respectively, were phototoxic to Colo-26 cells in culture. The toxicity of the dyes 2-4 was evaluated in clonogenic assays of human carcinoma cell lines. Importantly, the presence of a sulfur, selenium, or tellurium heteroatom in the molecules had no predictable impact on the toxicity of any particular dye set. Substituents at the 2-, 4-, and 6-positions of the dye had a much greater impact on cytotoxicity. The IC(50) values determined in the clonogenic assays did not correlate with chemical properties in the dye molecules such as reduction potential or lipophilicity. Initial in vivo toxicity studies showed no toxicity for these dyes at dosages between 7.2 and 38 micromol/kg in BALB/c mice.

Fine motor control: An EMG study of ability of the thumb in healthy hands of adult subjects.

An EMG basic method of testing the fine motor control of the hand, a necessary clinical request, is needed to provide a practical approach on normal neuromuscular observations of the fine motor control parameters in order to interpret the harmonious motor functioning of the central and peripheral nervous systems. In this EMG study, predetermined voluntary writing movements were used to demonstrate various degrees of fine motor control (FMC) over the final common pathway in the abductor pollicis longus (APL) of healthy adult subjects. The effect of optimal motor control to isolate and maintain a single motor unit in the APL during motions of the thumb requiring different types of contractions, the speed of motions of the thumb, and the intensity of segmental muscular EMG activity of the first dorsal interosseus (1DI) and the opponens pollicis (OP) is researched. Observations led to the establishment of percentage levels of FMC achievements. The perfect FMC in the APL can be achieved in any of the tests given. However, each test has its own level of success and, therefore, its own degree of difficulty. The means of success of FMC of this group, being 80%, demonstrate the feasible degree of the testing procedure. Analyses of the means and of the frequency distribution of subjects related to levels of success of each static and dynamic test show increased FMC difficulty in fast continuous motions. Voluntary writing without assistance has a tendency to be faster in eccentric than in concentric contraction of the APL. The means of 1DI and OP stay at the light level of muscular intensity even in a fast upward writing motions, where these muscles should have primary or assistant roles. This illustrates the importance of testing the FMC in a highly coordinated task such as writing while dynamic elements of muscular contractions influence the motor control, and are affected by the FMC.

Human abductor pollicis brevis muscle "divisions" and the nerve hila.

The interpretation of neuromuscular impairment may be aided by an analysis of functional anatomic factors. The anatomy of the abductor pollicis brevis (APB), a muscle used for skilled movements, was investigated in 19 embalmed hands, and the muscular divisions joining the common tendon at different sites were reproduced on clear vinyl sheets. The median nerve pathway to thenar muscles was followed to where it divides to the APB nerve and to the sites of the main terminal hila. Transverse (x) and longitudinal (y) muscle axes were established with the aid of landmarks to reproduce the nerve pathway on the skin surface. In the rather thick APB, three groups of six muscular heterogeneous divisions were regularly present. The dorsal aponeurotic expansion of the thumb receives the first group. The second group forms a continuous vertical line from the base to the body of the first phalanx. The outside site of its lateral tubercle takes the central tendon from the penniform third group. Hence, a reverse figure-seven distal insertion can be observed. The deepest medial (V2) and the most superficial lateral (V3) divisions had the highest mean diameters. The APB nerve fell between V2 and V2' and its line of projection supplied a guideline to establish an x axis at the proximal one-third of the muscle. The nerve hila plotted in relation to the x-y axes revealed a mode of location. The classical description of a thin APB muscle, made up of two bellies of parallel fibers seems incorrect. The APB nerve is not found on the deep aspect of the muscle as stated earlier, but within the muscle. The well-innervated muscular divisions point to the possibility of their individual use. The APB neuromuscular projection to the skin should allow more accurate fundamental EMG studies of the thumb and therefore provide a basis for more effective treatment in cases of impaired APB.

Muscular compensatory mechanism in the presence of a tendinitis of the supraspinatus.

The aim of this study was to assess the electromyographic (EMG) activity of the middle part of the deltoid and of the supraspinatus muscles in subjects suffering from supraspinatus tendinitis. This experimental group (N = 10) was compared to a control group (N = 10). Each subject performed three isometric contractions for each of four pre- determined levels (5, 20, 35 and 50%) of their maximal voluntary contraction (MVC) during shoulder abduction. These contractions were carried out at angles of 0 degree and 45 degrees of abduction. The EMG signals obtained for each subject were integrated and normalized in a Z score form. Trend analysis, performed on the data of each of the two groups, revealed the existence of a significant (p less than 0.001) linear relationship between the integrated EMG (IEMG) and torque levels for each muscle investigated, at both angles of abduction. Furthermore, in the control group, similar EMG amplitudes were obtained for each muscle at these two angles of abduction. However, in the experimental group, the IEMG of the deltoid muscle showed a significant decrease in activity relative to the activity of the supraspinatus at an angle of 45 degrees of abduction (ANOVA, p less than 0.05). It is suggested that this inhibition of the deltoid reflects a compensatory mechanism. The purpose of this mechanism could be to prevent the compression of the affected supraspinatus tendon between the humeral head and the acromion that could occur while abducting the arm.

Vibration influence on control of single motor unit activity.

Effects of vibratory stimulation and maximal isometric contraction on a fine motor control task were evaluated in 17 human subjects. Electromyographic audiovisual feedback cues derived from two fine-wire bipolar electrodes, inserted to a depth of 12 and 6 mm respectively, were used to train the subjects to isolate a motor unit in the extensor carpi radialis brevis muscle. A specially designed compressed air driven vibrator providing vibratory stimulation with an amplitude of 2 mm and a frequency range of 120-160 cycles per second was applied to the muscle tendon. A significant decrease was found in the subjects; ability to isolate the pretest motor unit during and after continuous and interrupted periods of vibration and following a maximal isometric contraction of the extensor carpi radials brevis muscle. Individual variations in the subjects' responses to the forms of application of the vibratory stimulus, electrode preference and feedback specificity were observed. Results suggest that marked spatial recruitment of motor units, brought into action by the vibration stimulus or by the maximal isometric contraction, interfered with inhibitory mechanisms necessary to achieve isolation and control of a single motor unit. A therapeutic application of vibration, based on the marked spatial recruitment observed during and after vibration, is proposed for muscle reeducation.

Hand orthotic device influence on fine neuromuscular control.

With the aid of electromyography, voluntary control of fine neuromuscular activity of deltoid and extensor digitorum communis muscles was studied in patients with motor dysfunction of the upper limb. A sequential training procedure was carried out both while the patient was wearing and not wearing a hand orthosis, during a static posture and dynamic hand movements. There was no difference between the levels of neuromuscular control achieved while wearing and not wearing the orthotic device, but the quality of the neuromuscular control was superior in the proximal limb muscle to that in the more distal muscle.