Anisotropic focusing characteristics of microdomain structures within crystalline Sr(0.61)Ba(0.39)Nb2O6: the crystal ball.

We report the anisotropic focusing characteristics of a spherically configured region of microdomains that have been induced within a cubic-shaped crystal of Ce-doped Sr(0.61)Ba(0.39)Nb2O6. The internal spherical structure focuses extraordinary polarized light, but not ordinary polarized light. The spherical region, which is easily observed via scattering, is formed as the crystal cools after a repoling cycle through the Curie temperature, with an applied field. Analytic modeling of the thermal gradients that exist within the crystal during cooling reveals a small (<1 degrees C) temperature difference between the central and the outside regions. The similarity in shape between these temperature profiles and the observed scattering region suggests a possible mechanism for the growth of this spherical microdomained structure.

Pentobarbital-morphine anesthetic interactions in terms of intensity of noxious stimulation required for arousal.

BACKGROUND: Previous reports suggest that the outcome (synergism, antagonism, summation) of opioid-barbiturate interactions may depend on the depth of anesthesia. One aim of the present study was to determine whether pentobarbital, alone and in combination with morphine, blocks awakening caused by noxious stimulation in a dose-related manner: the more intense the noxious stimulation, the more pentobarbital is required to suppress the response. A second aim of the study was to determine whether the pentobarbital-morphine anesthetic interaction depends on the depth of anesthesia measured in terms of intensity of noxious stimulation required for behavioral arousal (recovery of the righting reflex). METHODS: Experiments were performed on rats, with the measure of anesthetic effect being suppression of the righting reflex. The noxious stimulus was pressure on the tail at four levels of intensity: 0.0, 0.25, 2.5, and 3.3 kg, generated with an Analgesy-Meter. Pentobarbital and morphine were injected intravenously via chronically implanted catheters. Dose-response curves for pentobarbital given alone and in combination with morphine were determined (by probit analysis) separately for each of the pressure levels. RESULTS: Pentobarbital, alone and in combination with morphine, blocked awakening caused by noxious stimulation of different intensities in a dose-related fashion so that more anesthetic was required to block awakening with more intense stimulation. The pentobarbital ED50 values were: 12.0, 19.5, 22.7, and 24.3 mg/kg for 0.0, 0.25, 2.5, and 3.3 kg pressure, respectively. The addition of morphine (1 mg/kg) reduced the pentobarbital ED50 values for 0.0, 0.25, and 2.5 kg pressure by 34% (P < 0.0001), 39% (P < 0.0001), and 21% (P < 0.005), respectively. No change was seen in the pentobarbital ED50 value at the maximal (3.3 kg) pressure level. CONCLUSIONS: The results suggest that the depth of anesthesia can be measured in terms of intensity of noxious stimulation required for arousal and that the outcome of barbiturate-opioid anesthetic interaction depends on the depth of anesthesia.

Analysis of single protoplasts and regenerated plants by PCR and RAPD technology.

We investigated the use of the polymerase chain reaction (PCR) and the associated random amplification of polymorphic DNA (RAPD) technique in the analysis of DNA and specific genes in plant cells at different stages of regeneration in in vitro cultures. We demonstrate that both procedures can be used to differentiate reproducibly between closely related species as well as to reveal levels of DNA polymorphism in regenerated plants. We also demonstrate that both procedures, using protocols that we have developed, are applicable at all tissue culture stages, from single isolated protoplasts to regenerated plants. Possible explanations for the variation levels detected in regenerated wheat plants are advanced.

Does midazolam inhibit the development of acute tolerance to the analgesic effect of alfentanil?

Alfentanil-midazolam analgesic interactions were studied in rats with continuous infusions or bolus injections of the drugs. Analgesia was determined by measuring the threshold of motor response to noxious pressure. The continuous constant-rate infusion of alfentanil demonstrated that after an initial peak, the analgesia profoundly declined due to the development of acute tolerance. When alfentanil (250 micrograms.kg-1.h-1) was given together with midazolam (3 mg.kg-1.h-1), the decline in the analgesic effect of alfentanil was attenuated. Following the 4 h period of the constant-rate (250 micrograms.kg-1.h-1) infusion of alfentanil, when acute tolerance was already developed, midazolam (3 mg.kg-1) given as a bolus injection enhanced the alfentanil-induced anesthesia. At the same time, when alfentanil was given as a bolus injection (30 micrograms.kg-1) with or without midazolam (3 mg.kg-1) also by bolus injection, no changes were seen to indicate an enhancement of the analgesic effect of alfentanil by midazolam. The results suggest that midazolam attenuates the development of acute tolerance to the analgesic effect of alfentanil.

Locomotor activity after recovery from hypnosis: midazolam-morphine versus midazolam.

This study was performed to test the hypothesis that sedation after recovery from pharmacologic hypnosis is less pronounced if hypnosis is induced with a midazolam-morphine combination compared with midazolam administered alone. Loss of the righting reflex was used as an index for the hypnotic effect and reduction of locomotor activity as an index for the sedative effect. One group of rats received midazolam (20 mg/kg i.v) and another group an equipotent (in relation to the hypnotic ef.fect) combination of midazolam (4 mg/kg i.v.) and morphine (1.3 mg/kg i.v.). The duration of loss of the righting reflex in the midazolam and midazolam-morphine groups was 30 +/- 3 and 28 +/- 2 min, respectively (mean +/- SE). The difference between the groups in locomotor activity after recovery from hypnosis was very pronounced. The locomotor activity in the midazolam-morphine group at 1 and 2 h was seven and five times greater, respectively, than in the midazolam group (P < 0.005). The profound difference in locomotor activity for the two treatment groups was explained on the basis of the difference in the outcomes of midazolam-morphine interactions with regard to hypnosis (synergism) and sedation (summation). When the animals recovered from hypnosis, the synergism of the drug interaction ceased to be a contributing factor.

Acute tolerance to the hypnotic effect of morphine in rats.

To demonstrate the development of acute tolerance to the hypnotic effects of morphine, loss and recovery of the righting reflex with a constant-rate morphine infusion was studied in rats. In one group of animals, brain and serum concentrations of morphine were detected (radioimmunoassay) at the time of loss of the righting reflex, and in another group, at the time of the reflex recovery. The morphine infusion at a constant rate of 14 mg.kg-1.h-1 caused a loss of the righting reflex in all animals that was achieved by 2.5 h. However, this level of response could not be maintained, and at 5 h it began to decline. All animals recovered the righting reflex by the ninth hour, despite the continuing morphine infusion. The morphine brain and serum levels at the times of loss and recovery of the righting reflex were not different. The results suggest a development of acute tolerance to the hypnotic effect of morphine, which is determined primarily by pharmacodynamic mechanisms.

Magnitude of acute tolerance to opioids is not related to their potency.

It was suggested that for a given analgesic effect, more potent opioids may produce smaller degrees of tolerance than those with lower analgesic potency. The use of opioids with high analgesic potency to reduce the rate of tolerance development would be an important therapeutic consideration. This study tested the hypothesis that the degree of acute tolerance to the analgesic effect of opioids is inversely related to their potency. In the experiments on rats, the analgesic effects of morphine, alfentanil, and sufentanil given by a continuous 8-h infusion at a constant rate, were determined by measuring the threshold of motor response to noxious pressure on the tail. The comparative degree of acute tolerance was determined on the basis of the decline in the level of analgesia at the end of the infusion period. Morphine 4 mg.kg-1.h-1, alfentanil 0.45 mg.kg-1.h-1, and sufentanil 0.0085 mg.kg-1.h-1 caused approximately similar increases in the pain threshold. The peak of analgesia could not be maintained; it declined by 74 +/- 6% (P less than 0.0001) with morphine, 86 +/- 6% (P less than 0.0001) with alfentanil, and 92 +/- 2% (P less than 0.0001) with sufentanil. The results indicate that the infusion of alfentanil and sufentanil, which differ from morphine by higher analgesic potency (by 10-fold and more than 100-fold, respectively), results in a decline in the degree of analgesia during infusion similar to that of morphine. These data reject the hypothesis that the magnitude of acute tolerance to the analgesic action of opioid drugs following their systemic administration is inversely related to their potency.

Acute tolerance in morphine analgesia: continuous infusion and single injection in rats.

This study aimed to determine whether the decline of the analgesic effect of morphine with a continuous infusion or that after a single injection correlates with the changes in brain concentration of morphine. The analgesic effect of morphine and its brain and serum concentrations were determined with a continuous 8-h infusion at a constant rate and after a single subcutaneous injection of the agent. The analgesic effect was determined by measuring the threshold of motor response to noxious stimulation. Brain and serum concentrations of morphine were detected by radioimmunoassay with the use of 125I-labeled morphine. With the constant-rate (4 mg.kg-1.h-1, intravenous) morphine infusion, the peak of analgesia could not be maintained: the increase in the pain threshold at 2 h was 1,003 g and at 8h was 286 g (a decrease in analgesia by 72%, P less than 0.0002). At the same time, the brain morphine concentration tended to increase, to 278 ng/g at 2 h and 329 ng/g at 8 h. After the single morphine injection (6 mg/kg, subcutaneous), recovery from analgesia occurred at a much faster rate than did the decrease in morphine brain concentration; the decrease in pain threshold was 79% at 90 vs. 30 min after the injection (P less than 0.0001), and the corresponding decrease in brain concentration was 28% (NS). The absence of correlation between analgesia and morphine brain concentration both with the constant-rate morphine infusion and after the single injection suggests the development of acute tolerance, which is pharmacodynamic in nature.

RFLP analysis of Zea mays callus cultures and their regenerated plants.

Tissue culture of the Zea mays inbred line A188 resulted in the regeneration of plants having a high level of phenotypic variation compared to seed-grown control plants. To determine how such variation was induced and whether this could be related to specific in vitro culture methods, callus cultures were established and maintained on different, commonly used culture media. Plants were regenerated and the genomic DNA of callus cultures and regenerants analysed for RFLP differences. The results show that regardless of the gene probe used, callus formation resulted in significant deviations from the DNA pattern normally found in seed-grown control plants. Alterations in gene copy number also occurred. As differentiation and organogenesis began, the level of DNA variation fell, and most of the regenerated plants showed a genetic similarity to the controls; those with RFLP differences were the somaclonal variants.

Molecular changes in protoplast-derived rice plants.

To determine whether regeneration of rice plants from protoplast culture induces DNA polymorphisms, progeny plants from direct regenerants of such cultures were examined for restriction fragment length polymorphisms (RFLP analysis). Significantly increased levels of DNA polymorphism were found compared with those in non-tissue culture control plants. Analysis with gene sequences representative of different functional domains, revealed that such polymorphisms are apparently widespread and not associated with any particular region. Analysis by comparative digestion with both methylation-sensitive and insensitive restriction enzymes revealed that methylation changes cannot be regarded as a major factor in the induction of these DNA polymorphisms.

Morphine and fentanyl anesthetic interactions with diazepam: relative antagonism in rats.

The anesthetic effects of morphine-diazepam and fentanyl-diazepam combinations as characterized by abolition of the movement response to noxious stimulation were studied in rats to test the hypothesis of antagonistic interactions between the components of these combinations. Noxious pressure on the tail was used to induce the response. Dose-effect curves were constructed for the drugs given alone and in combination. With the use of probit procedure ED50 values for single drugs and their combinations were determined, and the interactions were analyzed with algebraic (fractional) and isobolographic methods. It was found that both morphine and fentanyl have a less than additive (antagonistic) interaction with diazepam. In combination the sum of fractional doses was higher than a single-drug fractional dose, 1.67 versus 1.00 (P less than 0.05) for morphine-diazepam and 1.61 versus 1.00 (P less than 0.05) for fentanyl-diazepam. The observed antagonism is a relative one that does not increase the requirement for one agent upon the addition of another agent.

Sedative and hypnotic midazolam-morphine interactions in rats.

The midazolam-morphine interactions in relation to the sedative effect and in relation to the hypnotic effect were studied in rats. Two series of experiments (sedative and hypnotic) were performed. In the sedative series, doses that inhibited locomotor activity to 10% or more of the control level were determined when the agents were given singly or in combination. Dose-response curves were determined with a probit procedure. The ED50 values of both agents and their combination were compared with algebraic (fractional) and isobolographic analyses in one subseries of experiments. The effect of a small fixed dose of morphine (1/10 of ED50 value for the sedative effect) on the slope of the sedative dose-response curve for midazolam was determined in the other subseries. In the hypnotic series of experiments, doses (ED50) that blocked the righting reflex with drugs given separately and in combination were determined by a probit procedure and, as in the sedative series, compared with algebraic (fractional) and isobolographic analyses. Sedative interaction between midazolam and morphine was found to have a tendency for synergism (interaction coefficient of 1.56, P greater than 0.05) with decreased individual variability in the sedative response to the combination. Hypnotic midazolam-morphine interaction was highly synergistic with the interaction coefficient of 3.70 (P less than 0.0001). A difference in the outcomes of midazolam-morphine interaction regarding sedation and hypnosis suggests that underlying mechanisms for these two effects are different; therefore, they should not be regarded as only increasing depths of the same action.

DNA variation in tissue-culture-derived rice plants.

Regenerants of rice were examined by RFLP analysis to determine the occurrence and extent of somaclonal variation. DNA polymorphisms were observed both among plants regenerated from different callus cultures as well as among sibling plants derived from a single callus. Regardless of the basal medium, a higher degree of genetic instability was found among plants regenerated from callus cultures maintained for longer incubation periods (67 days) than among those from shorter incubation periods (28 days). Detailed analysis showed that in several regenerants, there was a close correlation among those plants exhibiting DNA rearrangements and those with apparent methylation changes. Such alterations were observed with both structural and housekeeping genes.

Diazepam--morphine hypnotic synergism in rats.

The effect of diazepam-morphine combination on the righting reflex was studied in rats. Doses of the drugs given alone and in combination that block righting reflex (RR ED50) were determined with a probit procedure. Brain concentrations following equieffective doses of the drugs administered separately and in combination were determined by radioimmunoassay. Equieffective intravenous doses and corresponding brain concentrations for the agents were compared with fractional (algebraic) and isobolographic analyses. Interaction between diazepam and morphine was found to be synergistic. It is not likely to be pharmacokinetic in nature.

An investigation into the role of 5-Azacytidine in tissue culture.

A major problem associated with cereal biotechnology remains the extreme difficulty of reliably and efficiently regenerating plants from protoplasts. Because of the assumed inverse correlation between levels of the modified nucleotide 5-methylcytosine in a gene and the degree of transcription, we report here on experiments to determine whether exposure of maize and tobacco cultures to the 5-methylcytosine analogue 5-Azacytidine (5-Azt) induces gene de-methylation and, as such, enhances tissue culture response, for example by increasing protoplast division frequency. The results show that whilst 5-Azt may be of use in expanding leaf areas capable of producing callus as well as increasing the amount of callus produced, in all other aspects 5-Azt is strongly inhibitory to growth at all but the lowest concentrations. Molecular analysis shows that no readily discernible changes in gene methylation status can be found, regardless of 5-Azt concentration or the gene probe used. Differences can, however, be found in methylation status between callus and developmentally determined tissues, irrespective of 5-Azt treatment. The results suggest that, apart from a very limited role, 5-Azt has no obvious use in tissue culture.

The association of dietary fat with serum cholesterol in vegetarians: the effect of dietary assessment on the correlation coefficient.

The biologic relation between dietary fats and serum cholesterol established in controlled dietary studies usually has not been found in cross-sectional studies of the general population. In vegetarian groups, dietary variables and serum cholesterol have been correlated significantly. To examine the role of technique of dietary assessment versus the dietary pattern of vegetarians, the authors studied the relation of diet with total serum cholesterol in 46 predominantly vegetarian adults in the Boston, Massachusetts, area in 1973-1974. The basis of the dietary information was 10-day diet records. Total serum cholesterol was positively associated with dietary cholesterol (r = 0.53) and saturated fatty acids (r = 0.50) in partial correlation analysis adjusted for age, sex, and triceps skinfold. The use of one-day dietary records lowered these correlation coefficients to about 0.3. Analysis of the components of variation of nutrient intake demonstrated that the vegetarians had a lower within-person variance, a higher between-person variance, or both compared with nonvegetarian study groups. Biologic responsiveness to dietary fat in the vegetarians was similar to that predicted by the Keys equation derived from nonvegetarians. Therefore, multiple-day averaging of dietary records and relatively smaller ratio of within-person to between-person variation in intake favor the detection of cross-sectional associations of diet with serum cholesterol.

Sympathetic blockade increases tactile sensitivity.

To determine whether tactile sensitivity of the normal skin is altered by suppression of sympathetic efferent activity, the effect of stellate ganglion block and epidural sympathetic block on touch threshold was studied. The study was performed on ten individuals with various chronic pain syndromes. Tactile sensitivity was measured in the normal skin area with the use of von Frey filaments and a two-alternative forced-choice procedure with a staircase presentation of touch stimuli. With stellate ganglion block, touch threshold decreased on the side of the block by 48.8 +/- 8.% (P = 0.002) without any significant change in the threshold on the healthy, nonblocked side (P = 0.003 for the difference between the sides). With epidural sympathetic block, touch threshold decreased to the same extent on the diseased and healthy sides, which were both affected by the block (46.2 +/- 11.4%, P = 0.027 and 47.7 +/- 12.5%, P = 0.032, respectively). The results show that sympathetic blockade increases tactile sensitivity. They also suggest that sympathetic efferent activity modulates the function of tactile receptors. It is hypothesized that the sympathetic modulation makes tactile receptors less sensitive to touch, less specific, and probably more prone to code tactile stimuli in such a way that the brain recognizes this code as pain.

Morphine--caffeine analgesic interaction in rats.

The ability of caffeine to modify the effect of morphine on motor response to noxious stimulation was studied in 195 rat experiments. Motor reaction responses to noxious stimuli were studied in three series of experiments with three different techniques of mechanical tail stimulation. In each series of experiments, dose-response curves for morphine (probit analysis) were determined with and without the addition of caffeine (30 mg X kg-1). It was found that caffeine decreased morphine ED50 values in all three series of experiments, from 1.1 to 0.6 mg X kg-1 (P less than 0.002), from 3.2 to 2.5 mg X kg-1 (P less than 0.01), and from 13.2 to 6.2 mg X kg-1 (P less than 0.002). When caffeine was used alone in a dose of 30 mg X kg-1, there were no significant changes in motor reaction responses with any of the three methods applied for the assessment of morphine-caffeine combinations. These data indicate that caffeine potentiates the inhibitory effect of morphine on motor response to noxious stimulation in rats. It has been suggested that the effect of morphine on the motor response to somatic noxious stimulation results primarily from activation of inhibitory control systems concerned with this response. Caffeine may modulate the antinociceptive effect of morphine by stimulating one of these systems.

Training non-psychologists in the treatment of sexual dysfunction with special reference to the training of marriage guidance counsellors.

This paper describes a study in which marriage guidance counsellors were trained in the treatment of sexual difficulties. This study is discussed in the wider context of the literature concerned with training issues in the treatment of sexual function problems. The results of the training programme give clear evidence that non-professionals can be trained to produce results similar to those of a professional and it is argued that issues discussed in the literature concerning the training of professionals in the treatment of sexual difficulties are also applicable to non-professionals.