Self-titration by cigarette smokers

An 11-week crossover study was carried out in which 12 subjects smoked high-nicotine (1·84 mg standard yield) and low-nicotine (0·6 mg) cigarettes after an initial period of smoking their usual brands with a medium-nicotine yield (mean 1·4 mg). Plasma and urine nicotine concentrations, carboxyhaemoglobin (COHb) concentration, puffing behaviour, 24-hour cigarette consumption, and butt nicotine content were measured. The changes in plasma nicotine and blood COHb concentrations showed that the smokers compensated for about two-thirds of the difference in standard yields when switched to either high- or low-nicotine cigarettes. Thus, compared with the medium-nicotine brand, the intake of nicotine and carbon monoxide was only about 10% higher when subjects smoked the high-nicotine cigarettes, which had a standard yield 30-40% higher than the medium brands; and only about 15% lower when they smoked the low-nicotine cigarettes, which had a standard yield about 50% lower than the medium brands. But nicotine content and urine nicotine concentrations followed a similar pattern. Changes in puffing behaviour and in 24-hour cigarette consumption were only slight.The results show clear evidence of both upward and downward self-titration of nicotine and carbon monoxide (and tar) intakes when smokers change to cigarettes with standard yields that differ over the range studied.     

Chemical and enzymatic properties of riboflavin analogues.

The chemical and enzymatic properties of 26 analogues of riboflavin are presented. These analogues include both endo- and exocyclically substituted isoalloxazines with redox potentials from -370 to -128 mV. Physical and chemical data such as the electronic absorption spectra, pKas, and redox potentials of the analogues are presented and are discussed with respect to preferred tautomeric and resonance forms. Like riboflavin, most of the analogues are shown to be catalytic oxidants of dihydro-5-deazaflavins. Analogue binding to egg white binding apoprotein has been quantitated and serves to determine the origins of binding site specificity for this protein. Nearly all of the analogues that possess D-ribityl groups are found to be processed to the FAD level by the flavokinase/FAD synthetase system of Brevibacterium ammoniagenes. Most extensively studied are the reactivities of the analogues with the NAD(P)H:flavin oxidoreductase of Beneckea harveyi. Many of the analogues are substrates in this enzymatic redox reaction, and a linear free energy-rate relation (log Vmax vs. E0' of the analogue) is seen that parallels similar relationships in the nonenzymatic oxidation of dihydro-5-deazaflavins. This suggests a common mechanism for the reactions of such diverse flavins as riboflavin, 5-deazariboflavin, and 1-deazariboflavin.     

The lipopolysaccharide (R type) as a common antigen of Neisseria gonorrhoeae. I. Immunizing properties.

The ability of R-type lipopolysaccharide (LPS), isolated from Neisseria gonorrhoeae colony type 4, to protect against infection with N. gonorrhoea colony type 1 (T1 isolates) in the mouse and chicken embryo was investigated. C57 black mice were immunized intraperitoneally with 50 microgram of LPS, and challenged intracerebrally with 10-20 LD50's of N. gonorrhoeae colony type 1. Immunized mice were significantly protected (P less than 0.01 to less than 0.05) against challenge with different T1 isolates of N. gonorrhoeae when compared with non-immunized mice. Mice, injected with succinylated or alkali-treated LPS were not protected against gonococcal challenges. In a second animal model, leghorn hens were immunized intravenously with three injections of 500 microgram of LPS followed by a booster of 2.5 mg 2 weeks later. Embryonated eggs obtained from immunized hens were protected against challenge with 5 x 10(3) - 1 x 10(4) LD50's of three different T1 isolates. When hens were injected with the chemically modified LPS, the embryos were not resistant to gonococcal challenge. The results of this study demonstrate the ability of R-type gonococcal LPS to provide protection against different T1 isolates of N. gonorrhoeae.     

Growth changes in endocranial capacity in the Cercopithecoidea and Hominoidea

On the basis of examination of 2588 skulls representing 15 genera (56 species) from the Cercopithecoidea, together with 973 skulls representing six genera (10 species) of the Hominoidea, grouped according to stages of dental development, the pattern of postnatal growth change in endocranial volume has emerged as constant throughout Old World Primates. The brain attains 80% of its adult size by the time the deciduous dentition is fully established; 90% by the time the first permanent molars erupt; 95% during the period of eruption of the premolars and second molars; and some 98 % by the time the last permanent teeth are erupting. This constancy in timing of postnatal endocranial growth contrasts with a progressive variation in parameters associated with brain weight-body weight relationship.     

Differences in the infectivity of Babesia incubated in plasma and serum and the role of glucose in prolonging viability

Babesia rodhaini was less infective to mice after incubation in rat serum than in rat plasma. This was explained by lower levels of glucose in serum than in plasma. Both serum and plasma were found to become metabolically depleted of glucose following prolonged contact with clotted and unclotted blood cells, respectively. When glucose concentrations in depleted samples were restored to those in freshly separated samples, infectivities of parasites were similar. This was shown for both B. rodhaini and B. argentina. Products of blood cell metabolism, produced when separation of plasma or serum was delayed for 24 h, were not shown to have any detrimental effects on the parasites. Average glucose values for plasma from rats and cattle were 153 mg/100 ml and 63 mg/100 ml, respectively, whereas serum and plasma remaining in contact with blood cells contained as little as 2 mg glucose/100 ml. Lactate values were correspondingly low in plasma and high in serum. Fibrinogen and platelets, factors involved in clotting, did not affect infectivity of B. rodhaini or B. argentina. The relevance of these findings to living babesial vaccines in which plasma- and serum-based diluents may be used is discussed.     

Higher-plant cyclic nucleotide phosphodiesterases. Resolution, partial purification and properties of three phosphodiesterases from potato tuber.

1. Three phosphodiesterases that are capable of hydrolysing 3':5'-cyclic nucleotides were purified from potato tubers. 2. The phosphodiesterases were fractionated by (NH4)2SO4 precipitation and CM-cellulose chromatography. The phosphodiesterases were resolved from each other and further purified by gel filtration in high- and low-ionic-strength conditions. 3. All three enzymes lacked significant nucleotidase activity. 4. Enzymes I and II had mol. wts. 240,000 and 80,000 respectively, determined by gel filtration, whereas enzyme III showed anomalous behaviour on gel filtration, behaving as a high- or low-molecular-weight protein in high- or low-ionic-strength buffers respectively. 5. All enzymes hydrolysed 2':3'-cyclic nucleotides as well as 3':5'-cyclic nucleotides. The enzymes also had nucleotide pyrophosphatase activity, hydrolysing NAD+ and UDP-glucose to various extents. Enzymes I and II hydrolyse cyclic nucleotides at a greater rate than NAD+, whereas enzyme III hydrolyses NAD+ at a much greater rate than cyclic nucleotides. All three enzymes hydrolysed the artificial substrate bis-(p-nitro-phenyl) phosphate. 6. The enzymes do not require the addition of bivalent cations for activity. 7. Both enzymes I and II have optimum activity at pH6 with 3':5'-cyclic AMP and bis-(p-nitrophenyl) phosphate as substrates. The products of 3':5'-cyclic AMP hydrolysis were 3'-AMP and 5'-AMP, the ratio of the two products being different for each enzyme and varying with pH. 8. Theophylline inhibits enzymes I and II slightly, but other methyl xanthines have little effect. Enzymes I and II were competitively inhibited by many nucleotides containing phosphomonoester and phosphodiester bonds, as well as by Pi. 9. The possible significance of these phosphodiesterases in cyclic nucleotide metabolism in higher plants is discussed.     

Vasoactive intestinal polypeptide stimulates nonovarian progesterone secretion in rabbits

Recent experiments conducted in this laboratory have shown that intravenous infusions of vasoactive intestinal polypeptide (VIP) induced significant increases in plasma progesterone (P) in female rabbits. The purpose of this study was to determine the organ source of this P and to clarify the mechanisms by which it is induced. Intravenous infusions of VIP (37.5, 75, and 150 pmol/kg per min for 60 min) produced acute dose-dependent increases in plasma P in intact estrous rabbits. In ovariectomized (OVX) animals, VIP infusion (75 pmol/kg per min) produced a P increase of the same magnitude. In animals both OVX and adrenalectomized (ADX), this VIP effect was eliminated. The only significant change noted in luteotropic hormone (LH) or follicle stimulating hormone (FSH) was a decrease in FSH immediately following VIP infusion (150 pmol/kg). VIP infusion significantly increased plasma cortisol in intact and OVX animals, but not in OVX/ADX animals. It is concluded that VIP primarily stimulates the adrenal component of P secretion in the rabbit, via mechanisms independent of LH or FSH.