Vitamin A and human cancer

In recent years there has been considerable interest in the possibility that preformed vitamin A (retinol) or its precursors (carotenoids) protect against human cancer. Some synthetic analogues of vitamin A (retinoids) have been shown to prevent certain carcinogen-induced tumours in experimental animals. Case/control and prospective epidemiological studies in man have found that risk of cancer, including lung, gastrointestinal and bladder cancer is inversely related to estimates of dietary vitamin A intake. In most of the studies the estimates of vitamin A intake were crude and probably more closely reflect β -carotene intake than total vitamin A intake. This has led to the suggestion that β -carotene may be a protective factor.
Serum retinol and carotenoid concentrations are frequently reduced in cancer. This appears to be largely a consequence of cancer. Patients with advanced disease have lower serum concentrations than those with early disease. Furthermore, recent prospective studies have failed to find low serum retinol, at the time of the study, in people who subsequently developed cancer. Liver retinol reserves are similar in cancer and several other disease stales.     

Effect of clonidine on gastric emptying of liquids

We have investigated the effects of clonidine on gastric emptying of liquids in 30 patients. In a double-blind, randomized design, clonidine 150 micrograms, morphine 10 mg or saline in 1 ml was given i.m. One hour later, the patient drank a paracetamol solution (1.5 g in 50 ml water). Venous blood samples were obtained every 15 min for 90 min thereafter. Plasma paracetamol concentrations were measured using high- pressure liquid chromatography and the area under the concentration- time curve was calculated. The degree of sedation and complications were recorded. The area under the curve for 0-60 min was significantly smaller in the morphine group than in the saline group (P = 0.002; 95% confidence interval (CI) for difference -1237 to -502 micrograms min ml- 1), whereas it was greater in the clonidine group compared with the saline group, although this was not significant (95% CI for difference - 423 to 1264 micrograms min ml-1). Arterial pressure was significantly lower in the clonidine group compared with the saline group. Both clonidine and morphine appeared to cause mild sedation. We conclude that clonidine 150 micrograms i.m. does not delay gastric emptying of liquids in a similar manner to morphine.      

Disposition and Pharmacokinetics of Isopropanol in F-344 Rats and B6C3F1 Mice

The absorption, metabolism, disposition, and excretion of isopropanol(IPA) were studied in male and female rats and mice. Animalswere exposed by iv (300 mg/kg) and inhalation (500 and 5000ppm for 6 hr) routes; additionally, IPA was given by gavageto rats only in single and multiple 300 and 3000 mg/ kg doses.In the rat approximately 81–89% of the administered dosewas exhaled (as acetone, CO₂, and unmetabolized IPA); approximately76% of the dose in mice was exhaled after iv bolus but 92% wasexhaled following inhalation. Approximately 3–8% of theadministered dose was excreted in urine as IPA, acetone, anda metabolite tentatively identified as isopropyl glucuronicacid. Small amounts of radiolabel were found in feces and inthe carcass. There were no major differences in the rates orroutes of excretion observed either between sexes or betweenroutes of administration. Additionally, repeated exposure hadno effect on excretion. However, both the route of administrationand the exposure or dose level influenced the form in whichmaterial was exhaled. Following exposure to 5000 ppm, a greaterpercentage of unmetabolized IPA was recovered in the expiredair than following exposure to 500 ppm, implying saturationof metabolism.     

Relationship between European Mitochondrial Haplogroups and Chronic Renal Allograft Rejection in Patients with Kidney Transplant

Mitochondrial DNA variants may contribute to differences in mitochondrial function, leading to an altered immune system. The aim of this study was to analyze the relationship between mtDNA haplogroups and the development of chronic allograft dysfunction in patients with kidney transplant. A retrospective observational study was carried out on 261 patients who received kidney transplant (114 had stable transplant and 147 patients developed chronic allograft dysfunction). DNA samples were genotyped for 14 mtDNA polymorphisms by using Sequenom''s MassARRAY platform (San Diego, CA, USA). Only European white patients within the N macro-cluster were included. Patients with haplogroups V (odds ratio (OR)=0.32; p=0.037) and J (OR=0.36; p=0.038) showed lower odds for developing CRAD than patients with haplogroup H. After adjusting for the most significant variables, haplogroups V and J tended to statistical significance (p=0.091 and p=0.067 respectively). This is a preliminary study in which mtDNA haplogroups seem to be implicated in susceptibility or protection for developing chronic allograft dysfunction.     

Intranasal immunization with yeast-expressed 19 kD carboxyl-terminal fragment of Plasmodium yoelii merozoite surface protein-1 (yMSP119) induces protective immunity to blood stage malaria infection in mice

Variable protection against malaria blood-stage infection has been demonstrated in mice following parenteral immunization with the highly conserved 19 kD carboxylterminal fragment of the merozoite surface protein-1 (MSP1₁₉) using CFA/IFA and other adjuvants. Here we show that intranasal immunization of BALB/C mice with yeast expressed Plasmodium yoelii MSP1₁₉ plus a mixture of native and recombinant cholera toxin B subunit, could induce serum MSP1₁₉-specific antibodies at titres ranging from 20 000 to 2 560 000. The Ig subclass responses were predominantly G1 and G2b. Intranasal immunization led to protection following challenge (peak parasitaemia < 1%) in mice with the highest MSP1₁₉-specific titre (≥ 640 000). In two of the three protected mice, a peak parasitaemia of 0.1%–1% was followed by a boost of the antibody response whereas one of the three protected mice did not boost its antibody response after a peak parasitaemia of 0.02%. In unprotected mice, antibody levels rose, then fell, following the detection of parasites in the peripheral blood. CD4⁺ T cell-depletion abrogated the ability of the mice to boost their antibody response following challenge. These data demonstrate the potential for intranasal immunization with MSP1₁₉ to protect against malaria .     

ALVEOLAR-ARTERIAL OXYGEN TENSION DIFFERENCES IN ANAESTHETIZED HORSES

Anaesthetized, laterally recumbent horses were found to havelarge alveolar-arterial oxygen tension differences. These differenceshad a rapid onset following the induction of anaesthesia andremained constant during the anaesthetic period both in horsesbreathing spontaneously and in those subjected to intermittentpositive pressure ventilation. It is suggested that the differencesmay result from mismatching of ventilation and perfusion dueto the effect of gravity on the pulmonary circulation and restrictedventilation of the lower lung. The large fall in cardiac outputfound may, if unaccompanied by a decrease in oxygen utilization,augment the alveolar-arterial oxygen tension differences bycausing a decrease in the mixed venous oxygen tension.