Cognitive and neuropsychiatric disease manifestations in MS.

Multiple sclerosis is associated with a wide array of behavioral problems. This brief overview begins with a summary of the pathophysiology and treatment of MS. Thereafter, sections are devoted to psychiatric syndromes and cognitive decline linked to MS.

Pathogenic T cells in MOBP-induced murine EAE are predominantly focused to recognition of MOBP21F and MOBP27P epitopic residues.

Myelin-associated oligodendrocytic basic protein (MOBP) is a central nervous system (CNS)-specific myelin constituent important in stabilizing the unique multi-layered structure of the CNS-myelin sheath. Although autoimmunity against MOBP has been associated with multiple sclerosis pathogenesis, anti-MOBP pathogenic T cells have been poorly investigated as compared to T cells against other encephalitogenic myelin proteins. We have recently determined MOBP15-36 as the major encephalitogenic epitope of MOBP for SJL/J mice.

Multiple-dose pharmacokinetics of pentoxifylline and its metabolites during renal insufficiency.

Objective: To characterize pentoxifylline (PTF) and metabolite disposition after multiple oral doses given two and three times a day to patients with renal dysfunction.

Design: An open-label, randomized, crossover, parallel group design.

Setting: Community-based clinical research center.

Protracted, relapsing and demyelinating experimental autoimmune encephalomyelitis in DA rats immunized with syngeneic spinal cord and incomplete Freund's adjuvant.

Experimental autoimmune encephalomyelitis (EAE) is a model for multiple sclerosis (MS). However, MS is a chronic, relapsing and demyelinating disease, whereas EAE in rats is typically a brief and monophasic disorder showing little demyelination. We demonstrate here that DA rats develop severe, protracted and relapsing EAE (SPR-EAE) after a subcutaneous immunization at the tail base with syngeneic spinal cord and incomplete Freund's adjuvant (IFA).

Induction of persistently demyelinated lesions in the rat following the repeated adoptive transfer of encephalitogenic T cells and demyelinating antibody.

A chronic relapsing model of demyelinating experimental allergic encephalomyelitis (EAE) was induced in Lewis rats by the repeated co-transfer of encephalitogenic, myelin basic protein (MBP)-specific T cells in combination with a demyelinating monoclonal antibody (mAb) specific for the myelin oligodendrocyte glycoprotein (MOG). In controls, repeated injections of 5 x 10(5) MBP-specific T cells at intervals of 18-21 days resulted in an increasing resistance to the induction of further episodes of EAE. However, intravenous injection of the mAb 4 days after each T cell transfer overcame this 'vaccination' effect and induced severe clinical relapses associated with an increasing and persistent neurological deficit.

Cerebrospinal fluid penetration of cefpirome in patients with non-inflamed meninges.

Twenty patients (mean age 52 +/- 12 years, mean weight 75 +/- 15 kg) scheduled for elective myelogram or spinal anaesthesia were enrolled to determine the cerebrospinal fluid (CSF) penetration of a new expanded spectrum cephalosporin antibiotic, cefpirome (HR-810). A single 2 g intravenous dose of cefpirome was administered as a bolus between 1 and 8 h before lumbar puncture. Blood samples were collected at 15 pre-determined times and a single CSF sample was obtained at the time of lumbar puncture.

Lack of interaction between cefpirome and alcohol.

An observer-blind randomized, placebo-controlled, crossover study was conducted in 22 healthy male subjects. They received 2 g cefpirome or placebo intravenously following an overnight fast. One hour later they consumed a single 0.

[Differential diagnosis of dementia diseases. A prospective clinical study with neuropathologic diagnostic verification].

We present clinico-pathological correlations for a consecutive series of 44 demented patients in the Vienna longitudinal study on dementia. Prospective clinical diagnosis used the DSM-III-R and the NINCDS-ADRDA criteria. Not only the clinical, but also the neuropathological diagnosis of DAT is based on exclusion criteria, and depends on the interpretation of minimal vascular lesions.

Multiple dose pharmacokinetics, safety, and tolerance of velnacrine (HP 029) in healthy elderly subjects: a potential therapeutic agent for Alzheimer's disease.

The pharmacokinetics, safety, and tolerance of 1,2,3,4-tetrahydro-9-aminoacridin-1-olmaleate (HP 029) a potential therapeutic agent for Alzheimer's disease, were assessed after multiple oral doses in a randomized double-blind, placebo controlled, ascending dose study in 56 healthy elderly men (14 per dose group). The subjects in the first three groups received 25, 50, or 100 mg two times a day and a fourth group was administered 100 mg velnacrine tid for 28 days. All subjects received a final dose on day 29.

The effect of food on the bioavailability of velnacrine (HP 029) in healthy elderly men: a potential Alzheimer agent.

Velnacrine (HP 029; 1,2,3,4-tetrahydro-9-aminoacridin-1-ol-maleate) is an investigational drug being studied in patients with Alzheimer's disease. In this open, randomized, crossover study, 24 healthy, elderly men were given 100 mg of velnacrine on two different study days to assess the influence of food on the bioavailability of velnacrine. On the first day, subjects received drug either after an overnight fast or 15 minutes after completing a standard breakfast.

Single dose safety, tolerance, and pharmacokinetics of HP 029 in healthy young men: a potential Alzheimer agent.

1,2,3,4-tetrahydro-9-aminoacridin-1-ol maleate (HP 029) is a new cholinergic compound that has been shown to enhance memory in animals and therefore may be potentially effective in humans for the treatment of Alzheimer's disease (AD). The initial safety, tolerance, and pharmacokinetics of HP 029 after single oral doses were assessed in a randomized, double-blind, placebo controlled study in 70 healthy young men (eight dose groups). The test doses ranged from 5 to 200 mg.

Pharmacokinetics of roxithromycin (RU 965).

This report contains the findings of five studies performed to evaluate the pharmacokinetics of roxithromycin (RU 965), a new macrolide antibiotic. Roxithromycin was given as 150- and 300-mg film-coated tablets. The drug is rapidly absorbed after oral administration.

The pharmacodynamics and pharmacokinetics of multiple doses of the new H2-receptor antagonist, roxatidine acetate, in healthy men.

Roxatidine acetate (HOE 760, TZU 0460) is a new H2-receptor antagonist which is more potent than cimetidine and ranitidine. A randomised, double-blind, placebo-controlled study was conducted in healthy men to determine the effects of multiple oral doses of roxatidine acetate on unstimulated gastric acid secretion, and to assess the preliminary multiple-dose pharmacokinetics of its active desacetyl metabolite. The subjects were randomised to receive either roxatidine acetate 150 mg or placebo daily at 9 pm for 14 days.

Roxithromycin: a pharmacokinetic review of a macrolide.

In humans, roxithromycin is rapidly absorbed from the gastrointestinal tract producing peak levels (Cmax) within 2 h. The drug is eliminated with a half-life (T1/2) of about 10 h. Roxithromycin is not extensively metabolized.

Pharmacokinetics of orally administered pentoxifylline in humans.

The pharmacokinetics of pentoxifylline was studied in healthy male volunteers following single oral doses of 100, 200 and 400 mg of the drug in solution. Concentrations of the drug and three of its metabolites were determined in plasma. The major urinary metabolite was also determined for 24 hours after dosing.

Metabolism of cefotaxime: a review.

Cefotaxime (CTX) sodium is a potent semisynthetic cephalosporin antibiotic that has an unusually broad spectrum of antibacterial activity. This paper discusses the metabolism of 14C-CTX in rats, dogs, and humans as well as in vitro studies in cells of rats and rabbits. Excretion of radioactivity was similar in the three species, with greater than 80% of the dose being recovered in urine.

The pharmacokinetics and bioavailability of nomifensine maleate in healthy men.

Two studies were conducted in normal male volunteers to establish the pharmacokinetic parameters for nomifensine maleate and to determine the bioavailability of the drug from the Merital capsule intended for U.S. marketing.

Fendosal (HP 129): a potent anti-inflammatory and analgesic compound.

Fendosal (HP 129) is one of a series of potent non-steroidal anti-inflammatory agents. Fendosal was compared with aspirin in several anti-inflammatory and analgesic bioassay procedures. Results indicate that fendosal has an anti-inflammatory activity 1.

Dibenz[b,e]oxepinalkanoic acids as nonsteroidal antiinflammatory agents. 3. omega-(6,11-Dihydro-11-oxodibenz[b,e]oxepin-2-yl)alkanoic acids.

Omega-(6,11-Dihydro-11-oxodibenz[b,e]oxepin-2-yl)butyric, -hexanoic, and -octanoic acids were evaluated in the carrageenan paw edema assay. The most active compound, the butyric acid analogue, was 1.80 times more potent than the hexanoic compound, 1.

Pharmacology of a new non-steroidal, anti-inflammatory agent: 6,11-dihydro-11-oxodibenz [b, e] oxepin-2-acetic acid (HP 549).

HP 549 is an orally effective non-steroidal anti-inflammatory agent with moderate analgesic and antipyretic activity. It is active in adjuvant-induced polyarthritis when given prophylactically or therapeutically. HP 549 also inhibits carrageenan-induced paw edema in the rat, an activity which is not altered by adrenalectomy.

Carboxyarylindoles as nonsteroidal antiinflammatory agents.

An extensive series of carboxyarylindoles has been evaluated for antiinflammatory activity in the carrageenin paw edema assay. The requirements for optimal antiinflammatory activity in this series are relatively specific: a central pyrrole nucleus with (a) a 3-carboxy-4-hydroxyphenyl moiety substituted directly on the nitrogen, (b) a 2-phenyl group (R2) with a substituent of low electronegativity, (c) absence of a substituent in the 3 position (R3), and (d) a system fused across the 4,5 positions (X), which is lipophilic, quasiplanar, and does not interact sterically with the N-phenyl group. One derivative, 3-(3-carboxy-4-hydroxyphenyl)-2-phenyl-4,5-dihydro-3H-benz[e]indole (42), has been selected for further study.