Radiolabeled octreotide

Octreotide is a synthetic analog of the peptide hormone somatostatin (SMS). A wide variety of tumors express enhanced numbers of SMS receptors, notably neuroendocrine tumors and lymphomas, but also some of the more common adenocarcinomas. Octreotide contains only eight amino acids, some of which are in the (D) configuration in order to enhance the stability of the molecule in vivo. Tyrosine and ATPA-containing analogs of octreotide have been synthesized and labeled with iodine-123 and indium-111, respectively, with the intention of targeting SMS receptor-containing tumors for diagnostic purposes. Both radiopharmaceuticals demonstrate a high sensitivity and specificity for these tumors, indicating a clinical role for these agents in management of these diseases. Lessons can be learned from the success of these agents when designing improved antibody-based molecules. Tumor uptake of radiolabeled octreotide is very rapid, occurring within minutes of administration. Blood clearance is also rapid, such that tumors are soon visible even in areas of high blood background. An interesting finding has been the differences between the pharmacokinetics of the iodinated and indium-labeled species. Although the majority of¹²³I-Tyr³-octreotide undergoes hepatobiliary excretion,¹¹¹In-DTPAPhe¹-octreotide is eliminated predominantly by the kidneys. These results suggest that the smallest possible antibody-like tracers are likely to have advantages over native immunoglobulins and conventionals Fab-like fragments.     

The effect of carbon monoxide on haem-facilitated oxygen diffusion

The aim of this paper is to quantify the effect of small quantities of carbon monoxide on the facilitated diffusion of oxygen by haemoglobin in the steady state. It is the first phase in the study of a mathematical model for carbon monoxide poisoning. Here we extend the Wyman model for facilitated diffusion to the case in which there are two ligands. The equations are solved using an asymptotic technique developed by Murray. We obtain accurate analytic approximations for the biologically important quantities of the problem for various percentages of carbon monoxide. These are the concentrations of free oxygen, haemoglobin, oxyhaemoglobin and carboxyhaemoglobin, and hence the saturation of the protein and the facilitated oxygen flux. The major effect of very small quantities of carbon monoxide on the oxygen flux is shown.     

A mathematical model for the population dynamics of army ants

A stochastic cellular automata model for the population dynamics of the army antEciton burchelli on Barro Colorado Island in Panama is set up. It is simulated on the computer and shown to give good agreement with biological data. It is analysed using two approximations akin to the mean field approximation in statistical mechanics, and good agreement with the simulations is obtained. Finally, the role of distance between successive statary phase bivouacs is discussed with regard to the rate of colony growth. There are two aspects of the biological system studied here that make it of general importance. First, the population is structured, since the size of each colony of army ants is crucial. Second, the spatial behaviour of the population, as in many others, is not diffusion-like, although it is random. This has implications for the kind of model that is chosen.     

Can morbidity associated with untreated asthma in primary school children be reduced?: a controlled intervention study.

OBJECTIVE--To determine whether an intervention programme based on existing school and community resources can reduce school absence and improve participation in games lessons and sport in children with unrecognised or undertreated asthma. DESIGN--Parallel group controlled intervention study. SETTING--102 primary schools in Nottingham: 49 were randomised to receive the intervention and 53 to be control schools. SUBJECTS--All children aged 5 to 10 years with parent reported absence from school because of wheezing in the previous year and taking no treatment or beta agonists only. INTERVENTIONS--Children with asthma were referred to their general practitioner for assessment of symptoms and treatment. Teachers were given education on asthma by the school nurse in 44 of the 49 intervention schools. MAIN OUTCOME MEASURES--Changes in school absence and missed games and swimming lessons because of wheezing, and schools'' policy towards management of asthma in school. RESULTS--Of 17,432 children screened, 451 met the entry criteria--228 in intervention schools and 223 in control schools. 152 (67%) children in intervention schools visited their general practitioner, of whom 39 (26%) were given a new diagnosis of asthma and 58 (38%) had treatment for asthma increased or changed. Over the next academic year mean (SE) parent reported school absence due to wheezing fell significantly, but to a similar extent, in both intervention and control schools (0.82 (0.11) and 1.09 (0.21) weeks respectively). There was little change in school recorded absence or participation in games lessons and swimming lessons in either group. At the end of the study intervention schools were more likely to have improved aspects of management of asthma in school. CONCLUSION--The intervention resulted in a majority of children being assessed by their general practitioner and improved teachers'' understanding and management of asthma, but it did not result in any appreciable reduction in morbidity.     

SURVIVAL OF MANX SHEARWATERS PUFFINUS PUFFINUS

The breeding success of Manx Shearwaters at Skokholm Island, Pembrokeshire, was followed in study burrows, and data on survival of the young were augmented by ringing large numbers as they were about to leave the island and recapturing them in later years.
The weight of the young at fledging and the date at which they leave affect their chances of survival; overall, as many as 30% of the young birds may survive to reach breeding age, which is thought to be normally about 5–6 years. Adult mortality varies between wide limits of about 5 and 20%, but juvenile survival appears to be of about the right order to balance adult losses.
The significance of the one-egg clutch is discussed. At the normal time of laying the female may not be able to obtain sufficient food to form a second egg. A two-egg clutch, laid at a later date, would not produce more surviving young since these would fledge too late in the season to have a good chance of survival.
The advantage of leaving the island at a heavy weight is discussed, and it is concluded that the fat stores laid down give heavy young a greater chance than light young of migrating a long distance without food. It is possible that the young may even reach their winter quarters (off Brazil) without having to feed on passage if they depart with enough stored fat.     

Hepatic injury in chronic iron overload. Role of lipid peroxidation

In both hereditary hemochromatosis and in the various forms of secondary hemochromatosis, there is a pathologic expansion of body iron stores due mainly to an increase in absorption of dietary iron. Excess deposition of iron in the parenchymal tissues of several organs (e.g. liver, heart, pancreas, joints, endocrine glands) results in cell injury and functional insufficiency. In the liver, the major pathological manifestations of chronic iron overload are fibrosis and ultimately cirrhosis. Evidence for hepatotoxicity due to iron has been provided by several clinical studies, however the specific pathophysiologic mechanisms for hepatocellular injury and hepatic fibrosis in chronic iron overload are poorly understood. The postulated mechanisms of liver injury in chronic iron overload include (a) increased lysosomal membrane fragility, perhaps mediated by iron-induced lipid peroxidation, (b) peroxidative damage to mitochondria and microsomes resulting in organelle dysfunction, (c) a direct effect of iron on collagen biosynthesis and (d) a combination of all of the above.     

In vitro rates of oxidation and gluconeogenesis from L(+)- and D(-)lactate in bovine tissues

Slices of bovine kidney cortex, liver, heart and sternomandibularis muscle actively metabolized D- and L-lactate. Rates of D-lactate oxidation were greatest in kidney cortex followed by heart and liver with muscle exhibiting the lowest rates. L-lactate oxidation was greatest in kidney cortex followed by heart with liver and muscle exhibiting similar rates. Rates of oxidation of gluconeogenesis were similar for D- and L-lactate at 0.1 mm lactate but D utilization, as a percent of L, decreased as substrate concentrations increased to 50 mM. Bovine tissues appear to possess significant potential for D(-)lactate utilization. Estimates of this and possible interactions are discussed.     

Centrifugal waste disposal and the optimization of ant nest craters

We considered how ant, Tapinoma simrothi, colonies dispose of the material generated by their nest excavations in nest entrance craters. We developed a model for optimum crater formation on both flat and sloping ground (although we have not solved it in full generality for sloping ground). We found that the ants, when working on flat ground, show a close approximation to this least costly waste disposal. Craters on slopes may not be optimal even though they will be cheaper to make than ones of a similar volume on level ground. We further tested the model with a manipulative experiment, which also suggested the simple rule of thumb that ants might use. In response to having one-quarter of their crater removed, the ants focused most of their further waste disposal in that quarter. This suggests that their rule of thumb may be to deposit material at the nearest point with an angle of elevation less than that of the optimal angle. This should generate symmetrical craters on flat ground. The model also makes certain additional and testable predictions about the fine structure of craters.