Rheumatoid arthritis and disk derangement of the temporomandibular joint. A comparative arthroscopic study.

Consecutive patients with clinical diagnoses of disk derangement and rheumatoid arthritis with temporomandibular joint (TMJ) signs and symptoms were compared by clinical, radiographic, and arthroscopic examination. Synovial biopsies were obtained from patients with arthroscopic features of synovial inflammation. No clinical sign or symptom was found to be specific of rheumatoid involvement although joint crepitation was most frequently found in rheumatic patients (p less than 0.001). Tomographic features of subchondral bone involvement were more frequently revealed in TMJs of rheumatic patients (p less than 0.001). At arthroscopy rheumatic patients often showed pronounced arthrotic changes and inflammation. In contrast to patients with disk derangement, fibrosis of the TMJ was frequent (p less than 0.001). Histologic examination of obtained synovial specimens correlated well with arthroscopic findings, and more pronounced inflammation was present in specimens from rheumatic patients.     

In vitro evaluation of acyloxyalkyl esters as dermal prodrugs of ketoprofen and naproxen

A series of acyloxyalkyl esters of ketoprofen and naproxen were synthesized and investigated as topical prodrugs with the aim of improving the dermal delivery of the drugs. In addition, some hydroxyalkyl esters of ketoprofen and naproxen were synthesized as possible intermediates of acyloxyalkyl prodrugs. All of the prodrugs were more lipophilic than their parent molecules, as evaluated by drug partitioning between 1-octanol and phosphate buffer at pH 7.4 (log Papp). However, their solubilities in aqueous solutions decreased markedly compared with the parent molecules. The prodrugs were stable toward chemical hydrolysis in aqueous solutions (pH 7.4), but were hydrolyzed to the parent drug both in 80% human serum and in human skin homogenate, with half-lives ranging from 4 to 137 min and from 13 to 403 min, respectively. The abilities of the selected naproxen acyloxyalkyl prodrugs to deliver naproxen through excised human skin were evaluated. Generally, the prodrugs showed similar dermal delivery as the parent drug through cadaver skin. In the present series of lipophilic prodrugs of naproxen, the prodrug with the highest aqueous solubility was the most effective prodrug to deliver naproxen through the skin.     

Male perceptions of female attractiveness: The effects of targets' personal attributes and subjects' degree of masculinity

This study examined the relationship between the degree of sexist beliefs held toward women by male subjects and their perceptions of attractiveness of females described as possessing either masculine or feminine personality characteristics. One hundred twenty-two undergraduate males were given the Macho Scale, the Auburn University Personal Behavior Summary, a biodata sheet, and were asked to judge previously rated photographs of women along a dimension of attractiveness. Results demonstrated that males perceived physically unattractive and average females described as affectionate and compassionate as more attractive than similarly rated females described as independent and assertive. High Macho subjects viewed females as less attractive than low Macho subjects. Physical attractiveness of the male subjects was largely unrelated to their ratings of the females.     

Baclofen: reduction of presynaptic calcium influx in the cat spinal cord in vivo

 In the ventral horn of the lumbar spinal cord of cats anaesthetised with pentobarbitone sodium, microelectrophoretically administered (–)-baclofen, but not (+)-baclofen, reversibly reduced the duration of the orthodromic action potential of muscle group Ia afferent terminations, but not those of muscle group I afferent myelinated fibres. The presumably submicromolar concentrations are already known to reversibly reduce excitatory transmitter release from muscle group Ia afferent terminations. Action potential durations were estimated from threshold recovery curves after an orthodromic impulse using an extracellular microstimulation technique. Both of these presynaptic effects of (–)-baclofen were blocked by baclofen antagonists, and neither appeared to be reduced by the potassium channel blocking agents tetraethylammonium and 4-aminopyridine. Tetraethylammonium and 4-aminopyridine also did not significantly modify the reduction by (–)-baclofen of monosynaptic field potentials in the lumbar cord of rats anaesthetised with pentobarbitone sodium. In the cat the maximum reduction by (–)-baclofen of termination action potentials was considerably less than that produced by cadmium ions, which, unlike (–)-baclofen, also reduced the action potential duration of group I myelinated fibres. These findings are consistent with a reduction by (–)-baclofen of the influx of calcium through voltage-activated channels in the membrane of group Ia terminations, a proposal which also accounts for the reduction by (–)-baclofen of the release of GABA at axo-axonic depolarizing synapses on these terminations. The results are discussed in relation to the mode of action of (–)-baclofen and the different sensitivities of transmitter release at various central synapses. Received: 30 May 1996 / Accepted: 11 September 1996     

A pharmacological study of group I muscle afferent terminals and synaptic excitation in the intermediate nucleus and Clarke's column of the cat spinal cord

Summary When administered microelectrophoretically GABA and piperidine-4-sulphonic acid depolarized the central terminations of muscle group Ia and Ib afferent fibres in the lumbar intermediate nucleus and Clarke's column of cats anaesthetised with pentobarbitone sodium. Both this depolarization, and primary afferent depolarization, generated by impulses in other primary afferent fibres which produce prolonged bicuculline-sensitive inhibition of the firing of group I afferent fibre-excited interneurones in the intermediate nucleus and cells in Clarke's column, are reduced by microelectrophoretic bicuculline methochloride. Systemically administered (±)-baclofen hydrochloride (maximum dose 8 mg kg^–1) depressed the monosynaptic excitation of Clarke's column neurones by impulses in muscle and cutaneous afferent fibres. Microelectrophoretically administered (–)-baclofen reduced the bicuculline-sensitive primary afferent depolarization of group I terminations without, however, reducing the depolarizing action of GABA or piperidine-4-sulphonic acid. The depression by (–)-baclofen of the group I monosynaptic excitation of intermediate nucleus neurones is not reduced by concentrations of bicuculline methochloride adequate to suppress prolonged inhibition of these neurones     

Modulation of mouse and human phenobarbital-responsive enhancer module by nuclear receptors

The constitutive androstane receptor (CAR) regulates mouse and human CYP2B genes through binding to the direct repeat-4 (DR4) motifs present in the phenobarbital-responsive enhancer module (PBREM). The preference of PBREM elements for nuclear receptors and the extent of cross-talk between CAR and other nuclear receptors are currently unknown. Our transient transfection and DNA binding experiments indicate that binding to DR4 motifs does not correlate with the activation response and that mouse and human PBREM are efficiently 'insulated' from the effects of other nuclear receptors despite their substantial affinity for DR4 motifs. Certain nuclear receptors that do not bind to DR4 motifs, such as peroxisome proliferator-activated receptor-alpha and farnesoid X receptor, can suppress PBREM function via a coactivator-dependent process that may have relevance in vivo. In competition experiments, mouse PBREM is clearly more selective for CAR than human PBREM. Pregnane X, vitamin D, and thyroid hormone receptors can potentially compete with human CAR on human PBREM. In contrast to the selective nature of PBREM, CYP3A enhancers are highly and comparably responsive to CAR, pregnane X receptor, and vitamin D receptor. In addition, the ligand specificities of human and mouse CAR were defined by mammalian cotransfection and yeast two-hybrid techniques. Our results provide new mechanistic explanations to several previously unresolved aspects of CYP2B and CYP3A gene regulation.     

Acute deafness. A complication of high-dose cisplatin

Acute, profound cisplatin-induced deafness has rarely been reported. Ototoxic reactions to cisplatin in the past have been subclinical, with most hearing loss occurring in the high-frequency range. A patient was treated with ultra-high-dose cisplatin who suffered acute profound deafness. Methods are suggested for preventing similar complications in other patients given cisplatin in high-dose ranges.     

Pinoline, a beta-carboline derivative in the serum and cerebrospinal fluid of patients with schizophrenia

Baseline levels of pinoline, 6-methoxy-1,2,3,4-tetrahydro-beta-carboline (6-MeOTHBC) in the serum and cerebrospinal fluid (CSF) were determined with GLC-mass spectrometry in 13 unmedicated schizophrenic patients and 18 non-psychiatric controls. A detectable concentration of 6-MeOTHBC was always present, but no differences were found between the schizophrenic and the control groups. The serum and the CSF levels of 6-MeOTHBC were not significantly related to such variables as sex, age, subtype of schizophrenia, the quality and/or intensity of the psychopathological symptoms, or the duration of illness. The role of the indoleamines in the aetiopathogenesis of schizophrenia is discussed.