Influence of chitosan and its glutamate and hydrochloride salts on naproxen dissolution rate and permeation across Caco-2 cells.

Chitosan and its glutamate and hydrochloride salts were evaluated for their efficacy in improving the dissolution behaviour of naproxen (a poorly water-soluble antiinflammatory drug) and its transport in vitro across Caco-2 cell monolayers. Drug-polymer physical mixtures and coground products, prepared at two different w/w ratios (30/70 and 10/90), were characterized by differential scanning calorimetry, X-ray powder diffractometry, scanning electron microscopy, and tested for dissolution properties. Coground systems were more effective than physical mixtures in improving drug dissolution and chitosan base, in spite of its lower water solubility, showed higher solubilizing power than its salts. According to the solid state analyses results, this effect was directly related to its stronger amorphizing power. Transport studies showed that only coground mixtures with chitosan glutamate salt allowed a significant drug apparent permeability improvement; however, they did not exhibit appreciable effects on the Caco-2 tight junctions (measured by the trans-epithelial electrical resistance variations), thus indicating that their enhancer effect was mainly due to an improved naproxen transport by transcellular passive diffusion rather than through the paracellular route. The direct compression properties and antiulcerogenic activity together with the demonstrated dissolution and permeation enhancer abilities toward naproxen make chitosan glutamate an optimal carrier for developing fast-action oral solid dosage forms of this drug.

In vitro and in vivo evaluation of carbamazepine-PEG 6000 solid dispersions.

The present work extended previous physico-chemical investigations on the effects of solid dispersion on the solubility, the dissolution rate and the pharmacokinetic profile of carbamazepine. Solubility studies showed a linear increase in carbamazepine solubility with the increase of PEG 6000 concentration. There is no marked difference between physical mixtures and solid dispersions for the enhancement of carbamazepine solubility by PEG 6000. Less than 60% of pure carbamazepine was dissolved in 90 min. Physical mixtures (carbamazepine phase III) and solid dispersions (carbamazepine phase II) dissolution rates were higher in comparison of the parent drug. The dissolution of carbamazepine phase III was more pronounced than that evoked by the phase II. The dissolution profiles indicated that the percentage of the drug dissolved was dependent on the proportion of PEG 6000. In solid dispersions there was a remarkable enhancement in the dissolution rates of the drug in the vicinity of the eutectic composition as compared with those of corresponding physical mixtures. Hence, the optimum value for the solid dispersion was 80.5+/-1.7% of carbamazepine having dissolved within the first 10 min compared to 40+/-1% for the corresponding physical mixtures of the same composition. Statistical analysis of pharmacokinetic parameters confirmed that the carbamazepine:PEG 6000 binary systems displayed higher bioavailability of the drug than the pure carbamazepine. The area under the curve (AUC) values highlighted the evidence that only slight differences in the bioavailability of the drug occur between physical mixtures and solid dispersions prepared at the 80:20 and 50:50 drug:carrier compositions. However, the mean normalized plasma concentrations showed that standard error deviations are rather wide intervals for pure drug and physical mixtures in comparison to solid dispersions. One additional interesting point to consider is the disappearance of the multiple peaks on the individual kinetic curves of the 50:50 solid dispersion composition. Furthermore, our investigations have highlighted the interest of solid dispersions prepared at <>-eutectic composition as our preliminary data show that the plasma concentration (C(5h)) of the drug for the 15:85 dispersed sample containing 150 mg of carbamazepine is not significantly different from that obtained for the 50:50 dispersed sample containing 300 mg of the drug.

Measuring exposure to racism: development and validation of a Race-Related Stressor Scale (RRSS) for Asian American Vietnam veterans.

This article describes the development and validation of the Race-Related Stressor Scale (RRSS), a questionnaire that assesses exposure to race-related stressors in the military and war zone. Validated on a sample of 300 Asian American Vietnam veterans, the RRSS has high internal consistency and adequate temporal stability. Hierarchical regression analyses revealed that exposure to race-related stressors accounted for a significant proportion of the variance in posttraumatic stress disorder (PTSD) symptoms and general psychiatric symptoms, over and above (by 20% and 19%, respectively) that accounted for by combat exposure and military rank. The RRSS appears to be a psychometrically sound measure of exposure to race-related stressors for this population. Race-related stressors as measured by the RRSS appear to contribute uniquely and substantially to PTSD symptoms and generalized psychiatric distress.

Premature treatment termination by angry patients with combat-related post-traumatic stress disorder.

Angry patients with conjoined post-traumatic stress disorder often direct their anger at health care providers during the course of treatment. Such misplaced anger can interfere with treatment. Emerging treatments for trauma-related anger are effective. However, even in the course of psychotherapy for trauma-related anger, these patients direct anger at their therapists, compromising the treatment alliance and increasing the likelihood of premature termination. A case example is presented to illustrate the effect of anger on the treatment alliance. A therapeutic strategy is proposed to reduce the likelihood of premature treatment termination in these high-risk patients. This strategy may also be helpful in primary care contexts.

[Bioavailability of phloroglucinol in man]. / Biodisponibilité du phloroglucinol chez l'homme.

This work reports a bioavailability study between two oral dosage forms containing 125.2 mg active phloroglucinol. Twelve healthy volunteers subjects received a sublingual administration of both dosage forms, a flash liberation tablet and a freeze-dried reference tablet (lyoc), according to a randomized and cross-over design. An accurate, sensitive and specific high performance liquid chromatographic method was developed for the determination of free phloroglucinol as well as its conjugated metabolites, that allowed as to clarify phloroglucinol pharmacokinetic behaviour in man, specially its important metabolisation, its poor systemic bioavailability after oral administration and its total urinary elimination mainly under metabolized form. Total plasmatic phloroglucinol pharmacokinetic profiles led to pertinent parameters needed for statistical bioequivalence study, i.e. T1/2 alpha, T1/2 beta, AUC, Tmax, Cmax and MRT. The mean comparative values of these parameters showed the equivalent performances of both oral dosage forms studied and the statistical tests performed (ANOVA, Westlake and two one-sided t test) concluded to their bioequivalence.

Compelled attention: the effects of viewing trauma-related stimuli on concurrent task performance in posttraumatic stress disorder.

We examined the ability of Vietnam veterans with PTSD to focus attention on a primary digit detection task while concurrently viewing neutral or Vietnam-related picture and word distractors. Controlling for combat exposure, military service, and psychopathology, veterans with PTSD took longer to detect the target when Vietnam-related pictures were distractors. There were no reaction time differences when word stimuli were distractors. The latency effect was specific to trials with trauma-related pictures and did not spread to neutral trials interleaved within a mixed block of trauma and neutral pictures. Individuals with PTSD recalled proportionally more Vietnam-related words than other groups, implying differential attention to Vietnam-related words. Attending to trauma-related pictures interferes with performance of a concurrent task by individuals with PTSD.

Head injury and combat-related posttraumatic stress disorder.

Given the association of injury and posttraumatic stress disorder (PTSD), we examined whether head injury might be associated with increased frequency and severity of PTSD. Using a mail survey, we queried 143 male combat veterans with and without PTSD, who had previously participated in PTSD research in our laboratory, about their history of head injury. Respondents with a PTSD diagnosis were significantly more likely to report a history of head injury than those without. Patients with a history of head injury also reported more severe symptoms of PTSD compared with PTSD patients without head injury. The association of head injury and PTSD was not due to greater combat exposure in the head-injured group. Head injury is associated with a greater likelihood of developing combat-related PTSD and with more severe PTSD symptoms. This retrospective study did not address mechanisms that could account for this finding. The results indicate head injury should be systematically assessed by both nonpsychiatric and psychiatric physicians concerned with the psychological sequelae of exposure to victimizing experiences.

Twenty-four-hour ambulatory blood pressure and heart rate monitoring in combat-related posttraumatic stress disorder.

This study examined the cardiovascular correlates of posttraumatic stress disorder (PTSD) in Vietnam combat veterans using 24-hr ambulatory blood pressure and heart rate monitoring. Veterans with PTSD (n = 11) exhibited significantly higher heart rate and diastolic blood pressure across the 24 hr than veterans without PTSD (n = 7) (80.8 vs. 71.9 bpm, and 80.1 vs. 71.5 mm Hg, respectively). Heart rate during sleep was also significantly higher among veterans with PTSD, compared to veterans without PTSD (71.0 vs. 62.7 bpm). These results, based on a more naturalistic measurement methodology used outside the laboratory, support an association between PTSD and increased chronic cardiovascular arousal.

Eye movement desensitization and reprocessing (EDMR) treatment for combat-related posttraumatic stress disorder.

Despite the clinical and social impact of posttraumatic stress disorder (PTSD), there are few controlled studies investigating its treatment. In this investigation, the effectiveness of two psychotherapeutic interventions for PTSD were compared using a randomized controlled outcome group design. Thirty five combat veterans diagnosed with combat-related PTSD were treated with either (a) 12 sessions of eye movement desensitization and reprocessing, EMDR (n = 10), (b) 12 sessions of biofeedback-assisted relaxation (n = 13), or (c) routine clinical care, serving as a control (n = 12). Compared with the other conditions, significant treatment effects in the EMDR condition were obtained at posttreatment on a number of self-report, psychometric, and standardized interview measures. Relative to the other treatment group, these effects were generally maintained at 3-month follow-up. Psychophysiological measures reflected an apparent habituation effect from pretreatment to posttreatment but were not differentially affected by treatment condition.

The Honolulu posttraumatic stress disorder stimulus set.

We present word and picture stimuli constituting a validated stimulus set appropriate for cognitive investigations of posttraumatic stress disorder (PTSD). Combat related and neutral words and pictures were rated by Vietnam veterans with PTSD and by three comparison groups along four dimensions: unpleasantness, Vietnam relevance, stressfulness, and memorability. There were distinctive patterns of responses by the PTSD group which efficiently discriminated the individuals in this group from those in the control groups. These stimuli have the potential to be developed as a diagnostic instrument.

Postdisaster psychosocial intervention: a field study of the impact of debriefing on psychological distress.

OBJECTIVE: Following a catastrophic natural disaster, the authors evaluated whether brief psychological intervention (debriefing 6 months later) reduced disaster-related psychological distress as measured by the Impact of Event Scale. METHOD: Two groups of subjects who had been exposed to Hurricane Iniki in Hawaii were assessed before and after participating in a multihour debriefing group. The intervention aimed to provide ventilation of feelings, normalization of responses, and education about normal psychological reactions to the disaster in a context of group support. To provide a partial control for the passage of time, the pretreatment assessment of the second group was concurrent with the posttreatment assessment of the first group. RESULTS: A repeated measures analysis of variance indicated that Impact of Event Scale scores were reduced in both groups after the treatment. CONCLUSIONS: There is preliminary empirical support for the effectiveness of postdisaster psychological intervention and for the feasibility of treatment research in postdisaster environments.

Cognitive-behavioral treatment for severe anger in posttraumatic stress disorder.

With a randomized group design, a 12-session anger treatment was evaluated with severely angry Vietnam War veterans suffering combat-related posttraumatic stress disorder (PTSD). Eight participants in anger treatment and 7 in a routine clinical care control condition completed multiple measures of anger control, anger reaction, and anger disposition, as well as measures of anxiety, depression, and PTSD at pre- and posttreatment. Controlling for pretreatment scores, significant effects were found on anger reaction and anger control measures but not on anger disposition or physiological measures. Eighteen-months follow-up (for both completers and dropouts) supported the posttreatment anger control findings. The challenges of treatment research with this refractory population are discussed.

Anger regulation deficits in combat-related posttraumatic stress disorder.

We describe a typology of regulatory deficits associated with anger in combat-related posttraumatic stress disorder (PTSD). Cognitive, arousal, and behavioral domain deficits in anger regulation were observed clinically in PTSD patients with high levels of anger who were participating in a multi-year trial of a structured anger treatment. We also describe a category of patients whose anger type we have termed "ball of rage." These patients exhibit regulatory deficits in all three domains of anger regulation. We offer a conceptual framework to advance the understanding of anger associated with PTSD and to guide its effective treatment.

Facial EMG responses to combat-related visual stimuli in veterans with and without posttraumatic stress disorder.

Veterans with (n = 10) and without (n = 10) posttraumatic stress disorder (PTSD) participated in an exploratory study of facial reactivity to neutral slides and to slides depicting unpleasant combat-related material that were previously determined to be emotionally evocative. It was found that the zygomaticus major (cheek), masseter (jaw), and lateral frontalis (forehead) muscles were especially reactive to the combat slides in the veterans with PTSD, suggesting the importance of facial emotional expression in this disorder. The PTSD participants' self-reports of overall distress paralleled these effects. However, autonomic reactivity did not reflect general arousal effects due to the visual stimuli, showing both the sensitivity of facial muscle assessment in this context and the need for further research on the relationship between stimulus modality and physiological trauma reactions. Additional directions for research in this area are discussed including efforts to correlate subjective and physiological reactions.

Characteristics of veterans in Hawaii with and without diagnoses of post-traumatic stress disorder.

A total of 118 combat veterans seeking services at the VA Medical Center in Honolulu were assessed on a variety of demographic and psychometric dimensions, permitting the first systematic comparison on the measured variables between veterans with and without PTSD in the multicultural population of veterans in Hawaii. The results have implications for medical interventions with this population.

Post-traumatic stress disorder as a sequela of Guillain-Barre syndrome.

Post-traumatic stress disorder (PTSD) was observed in a 24 year-old female following severe Guillain-Barre syndrome (GBS). A review of the literature uncovered no previously mentioned examples of PTSD resulting from GBS or other medical illnesses. GBS-induced PTSD shared the features of PTSD seen following other traumatic events.

Anger, impulsivity, and anger control in combat-related posttraumatic stress disorder.

Empirical evidence of a relationship between combat-related PTSD and increased anger is lacking. In this study, 24 veterans of the Vietnam War with posttraumatic stress disorder (PTSD) scored significantly higher on an Anger factor comprising multiple measures of anger than did comparison groups of 23 well-adjusted Vietnam combat veterans and 12 noncombat Vietnam-era veterans with psychiatric diagnoses. In contrast, the 3 groups did not differ significantly on orthogonal factors, one of which comprised cognitive impulsivity measures and the other of which reflected motor impulsivity. Changes in heart rate in response to provocation loaded positively on the Anger factor and negatively on the 2 Impulsivity factors. Concurrent depression and trait anxiety did not have an effect on level of anger in individuals with PTSD. These empirical findings support and extend the clinical evidence regarding PTSD and anger.