Gamma-irradiation stability of saturated and unsaturated aliphatic polyanhydrides--ricinoleic acid based polymers.

The effect of terminal sterilization by gamma-irradiation on several ricinoleic acid based polyanhydrides was investigated. The following polymers were used: poly(ricinoleic acid maleate) [P(RAM)], poly(ricinoleic acid succinate) [P(RAS)], poly(hydroxy stearic acid succinate) [P(HSAS)], poly(hydroxy stearic acid maleate) [P(HSAM)], and their copolymers with sebacic acid. The polymers were irradiated with an absorbed dose of 2.5 or 10 Mrad by means of a 60Co source under dry ice or at room temperature. No differences were found between samples irradiated under dry ice and at room temperature. Polymers prepared from monomers containing maleate residues, which contain double bonds adjusted to the anhydride linkage along the polymer chain, decreased in molecular weight, became insoluble, and showed fast hydrolytic degradation. For example, p(RAM), p(HSAM), and their copolymers with sebacic acid decreased in Mw from about 10,000 to about 2000, and from about 30,000 to about 5000, respectively, while polymers based on RAS and HSAS remained stable. This phenomenon was explained by an anhydride interchange-self-depolymerization process of the unsaturated anhydride bonds induced by gamma-irradiation. This explanation was supported by the depolymerization of another class of polymers having an anhydride bond between two double bonds, fumaric acid anhydride polymers. The anhydride bond that lies between two double bonds was found to be more sensitive to gamma-irradiation. This anhydride bond may be cleaved to form two radicals that further react with aliphatic anhydride bonds along the polymer chain to form inter- and/or intracyclization products.

Comparison of the enantioseparation of racemic uridine analogs on Whelk-O 1 and ChiralPak-AD columns.

The commercially available, brush-type (S,S)-Whelk-O 1 chiral stationary phase (CSP) has been used to separate 10 racemates of structurally related uridine analogs, potentially anti-viral agents, under various mobile phase compositions, using various temperatures. The enantioseparation was evaluated by comparing the Whelk-O 1 column performance with that of ChiralPak-AD column, reported previously. The comparison involved the role of some distinctive structural features of the racemates, type and composition of the solvent modifiers, as well as effect of temperature on the chiral discrimination. Despite the fact that both columns separate almost all the uridine analogs, significant differences were observed in their chiral recognition, as revealed from their retention, selectivity, resolution and elution order. The chiral recognition processes, responsible for enantioseparation on the Whelk-O 1 column, were relatively more systematic and easier to manipulate than on ChiralPak-AD column. Enantioseparation on the latter are of more complex nature and frequently gave results that were contradictory to the expectations. On the other hand, the performance in the ChiralPak-AD column was superior to that of the Whelk-O 1 column. Limitations in column handling and maintenance (pressure and temperatures) as well as limited solvent choice lead to the preference of the Whelk-O 1 column, in spite of its lower (but adequate) performance.

Resolution of enantiomers of uridine analogs, potential antiviral agents.

Racemic mixtures of 5-substituted carbocyclic analogs of uracil nucleosides, 2"- and 3"-furyl, 2"- and 3"-thienyl and 2"-selenienyl, potentially anti-viral agents, were resolved using amylose tris(3,5-dimethylphenyl)carbamate as the stationary phase. The mobile phase was n-hexane with ethanol or 2-propanol. Effects of some structural features on the extent of discrimination between the enantiomers were examined through the selectivity and resolution factors as well as the elution order. The structural features were as follows; the type and position of the hetero-atom O, S or Se, in the cyclopentadienyl substituent 5 of the uracil and hydroxymethyl vs. acetoxymethyl groups on the cyclopentene moiety of the uridine analogs. It appeared that effects of the structural features on the separation were solvent dependent, with some very unusual solvent effects. For example, average retention, which did not follow the polarity of the mobile phase modifiers, was much higher when ethanol was used compared to 2-propanol. Also, the elution order of the two enantiomers of several pairs was reversed when ethanol was changed to 2-propanol. In general, ethanol affected higher selectivity and resolution of all the enantiomeric pairs.

Electronic pressure algometry of deep pain in healthy volunteers.

Deep pressure pain threshold (PPT) and pressure pain tolerance (PPtol) were measured by pressure algometry at the mastoid processes, external malleoli, and sternum in 24 healthy volunteers. The algometer consisted of a force displacement transducer with a 0.25 cm2 pressure tip linked to a recorder. The rate of force application was approximately 1kg/sec/0.25cm2. High intersubject variation was noted at all sites for both PPT and PPtol. Mean PPT and PPtol values at the sternum were 5.2kg +/- 2.1 and 8.1kg +/- 2.4, respectively, and significantly higher than at the other sites. PTT did not differ significantly between the sexes or between dominant and nondominant sides. PPtol, on the other hand, was lower in the women, but significantly so only at the malleoli. On repeat examination, comparison between the mean values at each site showed no statistical differences in any instance. Pressure algometry, as used in this study in healthy subjects, proved a reliable technique for the estimation of deep PPT and PPtol values. It may possibly serve for screening the response to experimental pain in various groups of pain patients.

Diagnostic value of computer analysis of multipeaked EMG spikes.

Computer analysis of absolute number of peaks per second and the number of peaks in the multipeaked spikes/sec was carried out in the EMG interference recordings of 5 healthy, 6 myopathic and 8 neuropathic subjects. The purpose of the study was to detect diagnostically different patterns. A spike was considered multipeaked if it had 6 or more peaks. The amplitude of elimination (baseline) was examined at 1: 5, 1: 10 and 1: 15 of the average amplitude per second. Both the number of peaks and the number of peaks in multipeaked spikes in the neuropathic and myopathic muscles showed statistically significant differences when compared to healthy muscles. This technique could give an indication for the differential diagnosis of myopathic, neuropathic or healthy state of the muscle.

Fourier series analysis of the electrophysiological pattern of fatigue in healthy human beings, after curare administration.

Real time computer analysis of the electrophysiological development of muscular fatigue after small doses of d-tubocurarine (TC), has been examined in anesthetized human beings. As compared to a decrease of frequency in the control measurements, previous studies have shown an increase of the frequency of spikes after TC administration. The present experiments were carried out on the biceps brachii of 8 healthy human volunteers maintained in isometric contraction against a constant counter load until complete fatigue occurred. The Fourier spectrum analysis showed a statistically significant shift to lower frequencies before, and a milder statistically non significant shift after TC. These results may indicate that under mild curarization the early phase of muscular contraction requires a higher number of large motor units and thus, at a later stage of the contraction the pool of available large motor units becomes smaller. This conclusion supports the hypothesis that mild curarization causes a state of initial muscular fatigue.

Comparison of the electrophysiological pattern of fatigue between athletes required to perform explosive and endurance sports.

The electrophysiological behavior of an isometric contraction sustained to fatigue, was examined in 6 long distance runners and 9 athletes involved in explosive (burst) sports, by on line computer analysis of the electrical activity of vastus medialis, rectus femoris and vastus lateralis. The experiments were carried out with a counterload of 50% of the maximal strength of the muscle. The duration of spike increased and the frequency decreased in the 3 examined muscles, in both types of sport. In the burst sports the changes of value of both parameters were statistically significant in the 3 muscles. In endurance sports the variations of duration were not significant and the changes of frequency were statistically significant only in the vastus lateralis. These results could be explained by the gradual activation of motor units of more strikingly different sizes in burst sports. Thus it may be speculated that prolonged training in burst sports may result in the automatic mobilization of higher number of small motor units, for the initiation of contraction while in endurance sports the onset of contraction is more gradual and carried out by large motor units.

Effect of filter setting on the electromyographic parameters of muscles contracting to fatigue.

The effects of various filter settings on the electrophysiological behavior of the development of muscular fatigue were studied. Eleven healthy volunteers were examined during isometric contraction of biceps brachii and rectus femoris against a constant load until fatigue occurred. The electrical activity was taped and computer processing was carried out at the basic setting of 15-5000 cycles and at low (15-200 Hz) and high (200-5000 Hz) frequence filter. The results support the hypothesis that in the low range of frequencies there is a high density of large slow motor units, while in the high range of frequencies there are numerous small fast motor units.

Proximal monomelic amyotrophy of the upper limb.

A 30-year-old patient of Central European origin, suffering from monomelic amyotrophy, is presented. The disease was characterized by proximal weakness of one upper limb, mainly of the shoulder girdle, accompanied by atrophy. The electrodiagnostic examination revealed signs of partial denervation in the presence of normal motor and sensory conduction. The disease, which is probably of the anterior horn cells, had a benign course and good prognosis, as evident from repeated examinations during a follow-up of eight years.

Electrodiagnostic investigation of the neuromuscular lesions in rheumatoid arthritis.

85 muscles, in 30 rheumatoid arthritis patients, were examined by EMG. The patients were subdivided into steroid and non-steroid treated groups. In both groups, the EMG demonstrated myopathic, polymyositic and neuropathic lesions, the first two predominating. Similar changes were found regardless of the size of the muscle examined. A relatively high number of myopathic changes were observed in early RA. The activity of the disease did not seem to play an important role. No correlation with the condition of the adjacent joint was found. No patient had a normal EMG in all the muscles examined. The conduction velocity indicated an entrapment syndrome in four patients. Creatine phosphokinase was normal in 23 patients, while aldolase was moderately high in 9 of 23 cases.