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A Metz

Publications and source records attributed to A Metz.

At least 37 records · Page 2Linked to original sources
PubMed1995

Cytoprotective effects of CI-959 in the rat gastric mucosa: modulation of leukocyte adhesion.

BACKGROUND & AIMS: CI-959 is an anti-inflammatory agent that inhibits neutrophil adhesion, respiratory burst, and mast cell histamine release in vitro. In view of the emerging role of neutrophils in gastric erosive damage, the goals of this study were to assess the gastric cytoprotective effects of CI-959 and identify the mechanism responsible for this action. METHODS: Cytoprotective effects in the rat nonsteroidal anti-inflammatory drug and ethanol erosion models were assessed using image analysis. The in vivo effects of CI-959 on gastric acid secretion, arachidonic acid metabolism, and intracellular sulfhydryl and leukocyte adhesion were also examined. RESULTS: CI-959 protected prophylactically against the erosive damage induced by aspirin, indomethacin, and ethanol with 50% effective doses (ED50s) of 0.05, 1.0, and 0.07 mg/kg administered orally, respectively. When administered after indomethacin or ethanol, CI-959 had no effect on the healing of erosive damage. CI-959 did not alter gastric acid secretion, arachidonic acid metabolism, or intracellular sulfhydryl levels. In vivo, CI-959 blocked leukocyte adhesion in intravital microscopy studies using indomethacin (ED50, < 5 mg/kg orally) or platelet-activating factor (50% inhibiting concentration, approximately 10 mumol/L) as the adhesion stimulus. CONCLUSIONS: The most likely mechanism responsible for the cytoprotective effects of CI-595 is its inhibitory effects on leukocyte trafficking and/or adhesion.

Animals↗
PubMed1995

Psychosis in Parkinson's disease: diagnosis and treatment.

1. This article reviews the prevalence, diagnosis, pathophysiology and management of psychosis in Parkinson's disease. 2. Psychosis in Parkinson's disease has been associated with all antiparkinsonian medications. The most common symptoms are vivid disturbing dreams, visual hallucinations and paranoid delusions. 3. The emergence of psychosis reduces the patient's functional capacity and increases caregiver burden. It also poses a therapeutic dilemma because effective treatment of psychotic symptoms may result in worsening of motor symptoms and vice versa. 4. Increased physician awareness is essential for proper diagnosis and management. Withdrawal of anticholinergic medications and amantadine followed by levodopa dose adjustment is effective in many patients. 5. Atypical neuroleptics, in low doses, may be successful when other measures have failed. However, these agents are not approved for treating Parkinsonian psychosis and must be considered as investigational therapies.

Clozapine↗
PubMed1995

Cognitive performance on the Alzheimer's Disease Assessment Scale: effect of education.

The cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-Cog) is used to monitor disease progression and treatment efficacy in clinical trials of Alzheimer's disease (AD). Using data from a 12-week drug trial, we retrospectively studied the effect of education on ADAS-Cog performance in a group of 444 patients with AD. The effect of education was statistically significant on baseline ADAS-Cog total scores. This effect remained statistically significant after controlling for age, gender, and dementia severity. Education effects were also statistically significant at week 12 for ADAS-Cog total and 10 of 11 subitem scores in 138 AD patients in the placebo arm of the trial. Post hoc analysis showed that non-high school graduates performed worse than those with greater educational levels across a broad range of cognitive domains. Our results, in conjunction with reports linking lower educational level with a higher risk for AD, suggest that educational level of patients be given consideration in the design and interpretation of cognitive tests in AD drug trials.

Aged↗
PubMed1995

Anti-inflammatory properties of Gö 6850: a selective inhibitor of protein kinase C.

Protein kinase C (PKC) regulates a variety of signal transduction events implicated in the pathogenesis of inflammation, including the biosynthesis of inflammatory cytokines and superoxide and the activation of phospholipase A2. Because of the significant role of PKC in these inflammatory processes, we evaluated a specific and potent inhibitor of C kinase for efficacy in several in vitro and in vivo murine models of inflammation. Unlike the relatively nonspecific kinase inhibitor staurosporine, the bisindolylmaleimide 3-[1-[-3-(dimethylaminopropyl]-1H-indol-3-yl]- 4-(1H-indol-3-yl)-1H-pyrrole-2,5-dione monohydrochloride (Gö 6850) demonstrated increased selectivity for C kinase in purified enzyme assays (respective IC50 values (microM) for Gö 6850 and staurosporine: protein kinase C (0.032, 0.009); myosin light-chain kinase (0.6, 0.01); protein kinase G (4.6, 0.018); protein kinase A (33, 0.04); tyrosine kinase1 (94, 0.4); tyrosine kinase2 (> 100, > 1)). Topically applied Gö 6850 inhibited phorbol myristate acetate-induced edema, neutrophil influx and vascular permeability in murine epidermis in a dose- and time-dependent manner at levels comparable to indomethacin. In a murine model of delayed type hypersensitivity, Gö 6850 inhibited dinitrofluorobenzene-induced contact dermatitis with and ID50 value of 150 micrograms/ear. Cellular studies in mouse peritoneal macrophages demonstrated that Gö 6850 was a potent inhibitor of phorbol myristate acetate-induced prostaglandin E2 production. Superoxide production in phorbol myristate acetate-stimulated murine neutrophils was also inhibited by Gö 6850 (IC50 = 88 nM).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Anti-inflammatory properties of the protein kinase C inhibitor, 3-[1-[3-(dimethylamino)propyl]-1H-indol-3-yl]-4-(1H-indol-3-yl)-1H- pyrrole-2,5-dione monohydrochloride (GF109203X) in the PMA-mouse ear edema model.

Protein kinase C (PKC) mediates a number of intracellular signal transduction pathways implicated in the pathogenesis of inflammation, including phospholipase A2-dependent arachidonic acid release and eicosanoid production. Recent studies demonstrate that the PKC inhibitor GF109203X significantly reduces a number of inflammatory processes resulting from PKC activation by the topical application of phorbol myristate acetate (PMA) to mouse ears. In this model, GF109203X significantly reduced edema at doses similar to the PKC inhibitor staurosporine, and more effectively than indomethacin, zileuton, or sodium meclofenamate. Histological and biochemical analysis of biopsies from control and drug-treated ears revealed a marked reduction in edema, infiltrating neutrophils, and levels of the neutrophil-specific marker, myeloperoxidase, in GF109203X-treated mice. Prostaglandin E2 levels were also reduced in ears treated with GF109203X. These data suggest that GF109203X is an effective antiinflammatory agent as evaluated in the PMA model of edema, and implicates PKC as a potential target in the development of novel anti-inflammatory agents.

Animals↗
PubMed1991

Stress--mechanisms of immunosuppression.

Stress, a term commonly used to describe varied phenomena, should be restricted to describe an adaptive response by an animal to threats to homeostasis. The threats to homeostasis are called stressors. Stressors include a variety of physical, psychological, chemical, or infectious causes that are modified by intrinsic and extrinsic factors. Examples of modifiers include stressor severity, duration, novelty, host genetics and immune status. What may be a stressor to an animal in one situation, when modified, may not be a stressor in another situation. Mechanisms of stress once thought to involve a single pathway described by Seyle as the General Adaptation Syndrome, have been rejected. Four pathways, some incompletely defined, have been implicated in modulation of the immune system. They include autonomic nervous system, the hypothalamic adrenal axis, extra-adrenal pathways involving neuropeptides and neurotransmitters and neuroimmunological mediators. The mechanisms of stress-induced immunosuppression resistance are poorly defined in domestic fowl and will require careful experimentation linking defined stressors with altered physiological responses that affect specific immune function and result in increased disease susceptibility.

Adaptation, Physiological↗
PubMed1988

Postpartum panic disorder.

The literature on postpartum psychiatric disorders is limited to descriptions of depressive and/or psychotic syndromes. The authors describe three cases of panic disorder presenting for the first time in the early postpartum period. Clinicians should differentiate between postpartum panic disorder and the well-recognized presentation of postpartum depression.

Adult↗
PubMed1987

Multiple recurring uterocervical leiomyomas in two half-sibling Appaloosa fillies.

Two yearling, paternal half-sibling Appaloosa fillies were ovariohysterectomized for treatment of multiple uterocervical leiomyomas. The tumors recurred in both fillies, originating from cervical tissue that could not be removed at surgery. Previously reported cases of uterine leiomyoma in the mare have been of solitary tumors in older mares that were treated successfully by surgical removal.

Animals↗
PubMed1987

Inhibition of the rate of GABA synthesis in regions of rat brain following a convulsion.

1 The rate of synthesis of gamma-aminobutyric acid (GABA) in the cortex, hippocampus and striatum of rat brain was assessed by measuring the linear rate of accumulation of GABA following injection of amino-oxyacetic acid (AOAA). 2 Five min after a single electrically induced seizure there was a rise in GABA content in these brain regions and an almost total inhibition of the rate of synthesis. 3 Five min after seizure induced by the inhalant convulsant flurothyl there was no rise in GABA content in these brain regions but a similar marked degree of inhibition of GABA synthesis. 4 Two hours after the convulsion the rate of GABA synthesis had returned to control values in all three brain regions. 5 A single convulsion did not alter the glutamic acid decarboxylase activity in these brain regions either in the absence or presence of added co-factor (pyridoxal phosphate). 6 Evidence for an inhibition of GABA release following a convulsion which may be associated with the inhibition of GABA synthesis is presented in the following paper.

Aminooxyacetic Acid↗