Presence Of Biological Fluids Research Articles

Liposomes as carriers of drugs. Observations on vesicle fate after injection and its control.

Detailed knowledge of the behavior of liposomes (phospholipid vesicles) after injection is a prerequisite for their successful application as drug carriers in the therapy, prevention, or detection of disease (Gregoriadis, 1980). This discussion deals with two aspects: (1) the extent to which vesicles retain entrapped agents in the presence of biological fluids, namely, blood and (2) the rate by which vesicles are cleared from the circulation and their distribution in tissues. Evaluation of the first is likely to lead to methods of preventing or reducing agent leakage from the carrier en route to its target site. Study of the second aspect will contribute to the elucidation of the mechanism(s) through which vesicles leave the circulation to end up in tissues and also allow manipulations controlling vesicle clearance or uptake by tissues in need of pharmacological intervention. Both aspects have been discussed in detail elsewhere (Gregoriadis, 1983; Gregoriadis et al, 1983; Senior, 1987).

The meaning of sperm capacitation. A historical perspective.

It should be recalled that sperm capacitation was originally defined in 1952 as some physiological changes of the spermatozoa in the female genital tract before they are capable of penetrating and fertilizing the eggs. It was found further that capacitation can be achieved outside the female tract, first in the presence of biological fluids, and then in the absence of biological fluids. Later on it was found that capacitated rabbit uterine spermatozoa still have acrosome and that the acrosome reaction of rabbit spermatozoa occurred in contact with eggs in the oviduct. Thus, several authors separated acrosome reaction from capacitation and considered capacitation as a preparation for the acrosome reaction, even though the titles of their articles still implied that capacitation included acrosome reaction. During the past 30 years we have found many membrane changes on the molecular and immunological level in spermatozoa that prepare them for physiological changes such as "hyperactivation," and morphological changes such as "the acrosome reaction." These events lead to more vigorous motility and to the release of various enzymes for the penetration of the egg. Undoubtedly, further study will reveal more molecular, physiological, and morphological changes in the mammalian spermatozoa before they are capable of fertilization. There are definite changes before hyperactivation and acrosome reaction, but these changes are parts of capacitation, if we prefer to keep its original meaning. It is proposed here that in order to save further confusion, capacitation of spermatozoa should be defined as originally proposed, that is, to include all the events that lead to the development of the capacity of mammalian spermatozoa to penetrate eggs.(ABSTRACT TRUNCATED AT 250 WORDS)

Bacampicillin: a new orally well-absorbed derivative of ampicillin.

Bacampicillin (proposed international nonproprietary name), 1'-ethoxycarbonyloxyethyl 6-(d-alpha-aminophenylacetamido)penicillanate, is a new orally well-absorbed penicillin, highly active in vivo due to rapid transformation into ampicillin. The compound is stable in vitro at gastric pH and hydrolyzed slowly to ampicillin at neutral pH but very rapidly in the presence of biological fluids, e.g., tissue homogenates or serum. In vivo the transformation into ampicillin is so rapid that no unchanged compound could be detected in the blood after oral administration of bacampicillin to rats, dogs, and humans. On oral administration to mice, rats, and dogs, bacampicillin was found to be better absorbed than ampicillin, giving higher and earlier peak blood levels of ampicillin. The bioavailability of bacampicillin in rats and dogs was three to four times higher than that of an equimolar amount of ampicillin. On oral administration to rats, bacampicillin was found to give higher levels of ampicillin in organs such as the kidney, liver, and spleen than ampicillin itself. In "tissue cages" in rats, higher transudate levels of antibiotic were found after oral administration of bacampicillin than after ampicillin. On oral treatment of experimentally infected mice, bacampicillin was found to be more active than ampicillin.

Effect of Carbon Monoxide on the Biological Reduction of Nitrate

THE reduction of nitrate is accomplished by cells of very diverse types—plant, animal, and bacterial. A thermolabile catalyst controls the activation of nitrate, though cases are known where apparently nitrate may be reduced by biological means without the intervention of a specific catalyst.1 The distribution of the nitrate oxidase, as the catalyst may be conveniently termed, seems to be very haphazard; it occurs in the livers of most animals, but nitrate reduction in muscle is confined to the rat and guineapig. Among the bacteria, it is absent from obligate anaerobes and aerobes, but it occurs in most faculative anaerobes. With these organisms nitrate serves as an oxidising source and will enable anaerobic growth to occur in its presence.2 The nitrate oxidase is present in B. coli, the ability of which to reduce nitrate to nitrite has been made a test of its presence in biological fluids. The activity of the enzyme is greatly inhibited by traces of hydrogen cyanide,3 but if a suspension of B. coli which has been exposed to quite a high concentration of hydrogen cyanide is well washed with saline the organism regains its ability to activate nitrate.4 The effect of cyanide on nitrate oxidase is thus reversible.