Heparins as essential antioxidants

Chronically inflamed tissues contain significant concentrations of oxygen radicals, possibly generated by transition metal species such as Fe(II) and Cu(I). In addition, the pH of such tissues may well be lower than that of normal counterpart tissues. In this communication, the effect of variation of pH on the antioxidant activity of caeruloplasmin (a copper-containing acute-phase protein possessing important ferroxidase and other antioxidant activities) and of heparin are reported. Heparin, unlike caeruloplasmin, retains antioxidant activity at low pH. Heparins possess a variety of metal cation-binding chemical groups allowing them to bind damaging Cu(I) and Fe(II) ions and consequently prevent their redox involvement in oxygen radical-generating Fenton reactions. In conclusion, heparins may function as endogenous antioxidants and sequestration and/or oxidation by them, of ions such as Fe(II), may contribute to their effectiveness.

     

A possible cause of acquired immune deficiency syndrome (AIDS) and other new diseases

An hypothesis is proposed to explain the surge of new diseases appearing in the world. Mass immunization with live viral vaccines increases the probability of genetic recombination between live vaccine viruses and between live vaccine viruses and other viruses. Perhaps this is the reason for origination of new diseases within the last twenty years. Nucleic acid hybridization techniques might be used to test the hypothesis.     

p-Dimethoxy-substituted trans-octahydrobenzo[f]- and -[g]quinolines: synthesis and assessment of dopaminergic agonist effects

The N-n-propyl homologues of the title compounds were prepared for further assessment of the ability of the "p-dimethoxy" moiety to confer dopaminergic agonism upon a variety of ring systems. Both the angularly and the linearly annulated trans-benzoquinoline ring derivatives displayed prominent DA2 dopaminergic effects on the peripheral sympathetic nerve terminal and displayed postjunctional dopamine receptor agonist properties in the striatum. It is speculated that the angular octahydrobenzo[f]quinoline derivative (but not the linear octahydrobenzo[g]quinoline derivative) may owe its dopamine-like effects to metabolic activation phenomena. In contrast, the cis-fused isomer of the angularly annulated benzoquinoline was inactive, as was the simple benzene derivative N,N-di-n-propyl-beta-(2,6-dimethoxyphenyl)ethylamine.     

The POSCH data processing experience

Metadata, the term, may be new but metadata, the concept, is not new. For purposes of this paper, the term metadata is defined as the data used to define, store, retrieve, combine, analyze, and present the data values (the “real” data, so to speak). As clinical research studies get larger, it becomes desirable to use automated managers of the metadata. The Program on the Surgical Control of the Hyperlipidemias (POSCH), a national multiclinic clinical trial, manages most of its metadata manually but has been experimenting with ways to more fully automate them. Its Information Management System (IMS) is described with special emphasis on how it manages the metadata. The case is presented for further automation and standardization of metadata in large clinical research studies so that costs can be contained and smaller increments of “progress” can be measured. The concept of a Metadatabase Management System (MDBMS) is developed and illustrated using POSCH.     

Pharmacokinetics of vindesine bolus and infusion

Summary The pharmacokinetics of vindesine were investigated during treatment of 15 patients with progressive malignancies refractory to conventional treatment. Patients were administered one of three IV dose schedules: 3.0 mg/m² bolus injection, 1.2 mg/m²/day infusion for 5 days, or 2.0 mg/m²/day infusion for 2 days. Concentrations of the drug in the serum and urine were determined by radioimmunoassay. Serum concentrations were highest (5×10^-7 M) in patients receiving a bolus injection, but fell to nondetectable levels by 48 h in four of five patients (terminal t_1/2 15.0±9.4 h). Compared with bolus injection, 1.2-to 1.4-fold greater areas under the blood concentration curve were observed during infusions of 2.0 mg/m² and 1.2 mg/m². Whereas steady-state concentrations (1×10^-8 M) were maintained throughout the infusion of 1.2 mg/m²/day progressively increasing serum levels were observed during the infusion of 2.0 mg/m²/day. Serum concentrations fell rapidly following discontinuation of the 2.0-mg/m² infusion, but were somewhat more sustained in the 1.2-mg/m² infusion group. The average urinary excretion was similar for each dose-schedule (8%–11% of the total dose). The pharmacokinetics of vindesine are influenced by variations in dose schedule.     

Safety and efficacy of thulium laser resection of bladder tumors versus transurethral resection of bladder tumors: a systematic review and meta-analysis

Lasers in Medical Science - The thulium laser resection of bladder tumor (TmLRBT) is widely used in the treatment of non-muscle-invasive bladder cancer (NMIBC), and we conduct this study to compare...     

Enzyme activities associated with the demyelinating phase of canine distemper

Summary Canine distemper, a naturally occurring viral disease of dogs which often terminates in parainfectious demyelination, was used as a model to study the role of acid proteinase, neutral proteinase and beta-glucuronidase in demyelination. These enzymes were higher in cerebella of dogs with distemper-associated demyelination than in age-matched controls. The highest elevations corresponded with the most severely demyelinated cerebella. The source of the increased enzymes activities was apparently unrelated to the lymphocytes present in areas of demyelination.The direct effect of distemper virus and serum on these enzymes was tested in canine glial monolayers. Virus infection resulted in lower enzyme activities in cells concomitant with the appearance of cellular lesions. There was a relative increase of beta glucuronidase activity in the media suggesting that distemper virus released pre-formed lysosomal enzymes. Serum which was obtained from dogs with distemper-associated demyelination and had previously demyelinated cerebellar explants, also decreased activities of all 3 enzymesin vitro.The 3 enzymes were measured in gerbil brains at various time intervals following unilateral cerebral infarction to determine if processes other than demyelination also caused these enzymes to be increased. Uncomplicated ischemic necrosis (24 h post infarction) did not alter the activities of these enzymes. Invasion of macrophages to ingest and digest necrotic tissue 10 days after infarction resulted in greatly increased acid proteinase and beta-glucuronidase, but unchanged neutral proteinase, activities.It was concluded that the increased activities of acid proteinase and beta-glucuronidase in demyelinated tissue probably are derived from macrophages ingesting damaged tissue. Neutral proteinase may be more specifically involved in the demyelinating process since this is partially located within myelin and can degrade the basic protein of myelin.Supported in part by Research grant Nos. GM 1052 and Al-09022 from National Institutes of Health Service, U.S. Public Health Service.