Molecular pharmacology of 4-substituted glutamic acid analogues at ionotropic and metabotropic excitatory amino acid receptors

The pharmacology of (2S,4R)-4-methylglutamic acid, (2S,4S)-4-methylglutamic acid and (S)- and (R)-4-methyleneglutamic acids (obtained in high chemical and enantiomeric purity from racemic 4-methyleneglutamic acid by chiral HPLC using a Crownpak CR(+) column), was examined in binding experiments using rat brain ionotropic glutamate receptors, and in functional assays using cloned metabotropic glutamate (mGlu) receptors. As a notable result of these studies, (2S,4R)-4-methylglutamic acid and (2S,4S)-4-methylglutamic acid were shown to be selective for kainic acid receptors and mGlu receptors (subtypes 1alpha and 2), respectively, whereas (S)-4-methyleneglutamic acid showed high but rather non-selective affinity for the (RS)-2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionic acid (AMPA), kainic acid, NMDA and mGlu receptors (subtypes 1alpha and 2). Although none of the compounds were specific for any of the receptor subtypes, the results demonstrate that each of these structurally related compounds has a distinct pharmacological profile.     

Prevention of deformity during limb lengthening

Deformity occurs frequently at the site of distraction during leg lengthening and can add to disability. The elastic and nonelastic displacements have been measured in a model that simulates leg lengthening in the laboratory. Measurements have been made for different fixator systems. The angulation in the vertical plane that occurs during leg lengthening is minimized if the distance between the bone and the fixator bar is kept as small as possible, if three screws are inserted in the proximal and distal bone fragments, and if the peak loads on the fixator are reduced by adjusting the rhythm of distraction. However, even if these precautions are taken, the results show that some fixators designed for leg lengthening will fail and lead to deformity at the osteotomy site. This may occur under the repeated cycles of high loads associated with the rises in soft tissue tension that are known to occur in certain groups of patients. This study suggests that deformity can be prevented by the proper selection of a suitable frame and the adjustment of its configuration to meet the loading requirements.     

Challenge of BALB/c mice with respiratory syncytial virus does not enhance the Th2 pathway induced after immunization with a recombinant G fusion protein, BBG2NA, in aluminum hydroxide

The polypeptide of aa 130-230 of the G protein (G2Na) of respiratory syncytial virus (RSV) was fused to BB, the albumin-binding region of streptococcal G protein, producing BBG2Na, which induced protective immune responses in rodent models. Evaluation of the immune response in mice immunized with BBG2Na in the adjuvant alhydrogel revealed high amounts of interleukin (IL)-5 and some IL-4 in splenocytes restimulated in vitro. This is compatible with a Th2 response. The activation of the Th2 pathway in such mice was further supported by the detection of IL-5 and G2Na-specific IgE in vivo. Of interest, in contrast to immunization with formalin-inactivated RSV, immunization of mice with BBG2Na followed by intranasal RSV challenge did not lead to increased production of IL-5- or G2Na-specific IgE. However, IgG1- and IgG2a-specific antibodies were boosted. These results demonstrate that the Th2 pathway is not enhanced by RSV challenge in BBG2Na-immunized mice.     

Escalation of a fetish: coprophagia in a nonpsychotic adult of normal intelligence

The possibility of a dyschondroplastic syndrome should be considered in any patient presenting with a cartilagenous tumor in the head and neck. Classification of the patient as Maffucci's syndrome or Ollier's disease increases the need for vigilant observation for the development of sarcomatous lesions and can help differentiate between low-grade chondrosarcoma and atypical enchondroma.     

Comorbidity and course of psychiatric disorders in a community sample of former prisoners of war

OBJECTIVE: The authors assessed DSM-III-R disorders among American former prisoners of war. Comorbidity, time of onset, and the relationship of trauma severity to complicated versus uncomplicated posttraumatic stress disorder (PTSD) were examined. METHOD: A community sample (N=262) of men exposed to combat and imprisonment was assessed by clinicians using the Structured Clinical Interview for DSM-III-R. RESULTS: The rates of comorbidity among the men with PTSD were lower than rates from community samples assessed by lay interviewers. Over one-third of the cases of lifetime PTSD were uncomplicated by another axis I disorder; over one-half of the cases of current PTSD were uncomplicated. PTSD almost always emerged soon after exposure to trauma. Lifetime PTSD was associated with increased risk of lifetime panic disorder, major depression, alcohol abuse/dependence, and social phobia. Current PTSD was associated with increased risk of current panic disorder, dysthymia, social phobia, major depression, and generalized anxiety disorder. Relative to PTSD, the onset of the comorbid disorders was as follows: major depression, predominantly secondary; alcohol abuse/dependence and agoraphobia, predominantly concurrent (same year); social phobia, equal proportions primary and concurrent; and panic disorder, equal proportions concurrent and secondary. Trauma exposure was comparable in the subjects with complicated and uncomplicated PTSD. CONCLUSIONS: The types of comorbid diagnoses and their patterns of onset were comparable to the diagnoses and patterns observed in other community samples. The findings support the validity of the PTSD construct; PTSD can be distinguished from comorbid disorders. Uncomplicated PTSD may be more common than previous studies suggest, particularly in clinician-assessed subjects exposed to severe trauma.     

Gastric myoelectric and motor activity in dogs after isoflurane anesthesia

To characterize the effects of isoflurane on gastric motility, gastric electrical and contractile activities were assessed in six healthy adult dogs before and after recovery from anesthesia. Baseline recordings (fasting and fed state) were obtained in unanesthestized dogs 8 days after implantation of serosal electrodes and strain-gauge force transducers. After an overnight fast, dogs were anesthetized with 1.3 minimum alveolar concentration (MAC) isoflurane for 4.5 hours (approximately 6 MAC hours). No other anesthetic or sedative drugs were administered. During anesthesia, ventilation was mechanically controlled to maintain arterial carbon dioxide tension at 36 +/- 4 mm Hg. Gastric electrical and contractile activities (fasting and fed state) were recorded again 18 hours after recovery from isoflurane anesthesia. Recordings were analyzed to determine gastric slow-wave frequency, presence of slow-wave dysrhythmias, slow-wave propagation velocity, coupling of contractions to slow waves, a motility index based on relative contractile amplitudes, and onset and duration of contractions after a standardized meal. The only variable that was significantly decreased 18 hours after 6 MAC hours of isoflurane anesthesia was the gastric motility index during fasting-state phase III. This decrease was not apparent in the fed-state test periods. Our results suggest that, with the exception of gastric motility index during fasting-state phase III, variables for gastric electrical and contractile activities in dogs are unaffected by isoflurane 18 hours after anesthesia.