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Islet encapsulation devices serve to deliver pancreatic beta cells to type 1 diabetic patients without the need for chronic immunosuppression. However, clinical translation is hampered by mass transport limitations causing graft hypoxia. This is exacerbated in devices relying only on passive diffusion for oxygenation. Here, we describe the application of a cylindrical in vitro perfusion system to study oxygen effects on islet-like clusters immobilized in alginate hydrogel. Mouse insulinoma 6 islet-like clusters were generated using microwell plates and characterized with respect to size distribution, viability, and oxygen consumption rate to determine an appropriate seeding density for perfusion studies. Immobilized clusters were perfused through a central channel at different oxygen tensions. Analysis of histological staining indicated the distribution of viable clusters was severely limited to near the perfusion channel at low oxygen tensions, while the distribution was broadest at normoxia. The results agreed with a 3D computational model designed to simulate the oxygen distribution within the perfusion device. Further simulations were generated to predict device performance with human islets under in vitro and in vivo conditions. The combination of experimental and computational findings suggest that a multichannel perfusion strategy could support in vivo viability and function of a therapeutic islet dose.

Abstract: Much research has gone into developing a sustainable management tool for haemonchosis, namely the FAMACHA© system, which has been validated by numerous studies worldwide. However, the financial implications on production of implementing this system have not been fully investigated in sheep previously. A trial was conducted on a farm comprising a flock of approximately 300 Mutton Merinos on which the FAMACHA© system was in use. Seventy five maiden and multiparous ewes were randomly allocated to the following three trial groups: (i) FAMACHA© in which ewes judged to be in categories 4 or 5 were dosed with levamisole HCl 2.5% (Nemasol NF, Intervet); (ii) Conventionally dosed in which all ewes were dosed every six weeks with levamisole HCl 2.5% (Nemasol NF, Intervet); (iii) Suppressively dosed in which all ewes were injected every six weeks with moxydectin 1%m/v (Cydectin, Bayer AH). There were no significant differences in body weight gains, FAMACHA© and body condition scores amongst the three treatment regimens for ewes that did not conceive. For those that became pregnant during the trial there was a significant difference when analysed by calendar date but not when analysed by reproductive stage. There were also no significant differences between trial groups in lamb birth weight and, after slow growers had been sold, the average daily gain of the lambs born to ewes in the trial. The cost of anthelmintics was considerably lower for the FAMACHA© group. In conclusion there were no significant differences in selected production parameters when using the FAMACHA© system as opposed to other methods of anthelmintic use in a Mutton Merino flock in a semi-intensive farming system and that the gestation status should be taken into account when measuring these parameters in future studies. [Copyright &y& Elsevier]

Dietary potassium intake was estimated in 46 men and 88 women randomly selected from people aged 65 and over living in their own homes, and 24-hour urinary potassium, creatinine, and urea excretions were determined. The mean dietary potassium intake was 71 mEq/day in men and 54 mEq/day in women. There was a decline with age in both sexes. The sex and age differences were eliminated by expression of dietary potassium intake per unit lean body mass. Urinary potassium excretion averaged 51 mEq/day in men and 44 mEq/day in women, and again the sex difference and decline with age were abolished by expression of urinary potassium per unit lean body mass. There were highly significant relationships between dietary and urinary potassium. Consideration of the regression lines of these correlations suggested that if faecal potassium losses were 5 mEq/day, a negative potassium balance would be inevitable if dietary potassium fell below 27 mEq/day in men and 35 mEq/day in women. These findings are discussed in the light of experimental studies on dietary potassium restriction in man. [ABSTRACT FROM PUBLISHER]

Interleukin-8 (IL-8) attracts neutrophils into tissues and causes them to degranulate. Both menstruation and parturition involve neutrophil migration into uterine tissues and therefore IL-8 is a likely mediator of the tissue re-arrangements that accompany these events. We have examined the ability of endometrium explants and chorion cells in culture to synthesize and release IL-8 and the ability of progesterone, a synthetic progestin [medroxyprogesterone acetate (MPA)] and dexamethasone to inhibit this production. In endometrium, the stage of the menstrual cycle did not affect IL-8 production but a 10(-6) M concentration of progesterone or dexamethasone significantly reduced the concentration of IL-8 in medium after 24 h. After a further 24 h with lipopolysaccharide (LPS) stimulation, only MPA and dexamethasone inhibited production significantly. In chorion cells, IL-8 production was significantly decreased by both MPA and dexamethasone in the LPS stimulated cells but the reduction in the first 24 h was not significant. The IL-8 produced in uterine tissues might act synergistically with prostaglandin E (PGE), a likely site for this interaction being blood vessels where PGE production is also repressed by progesterone. Such a cooperative action would maintain low leukocyte entry into uterine tissues in the presence of progesterone and falling steroid levels would induce leukocyte immigration and activation with consequent tissue destruction. Such steroid-dependent interactions are important in our understanding of the mechanisms of menstruation and parturition and could allow new approaches to the treatment of uterine pathology. [ABSTRACT FROM AUTHOR]

Sixteen common biochemical estimations have been performed on nearly 500 people randomly selected from those over 65 living at home. The mean values and ranges found for serum sodium, potassium, chloride, bicarbonate, magnesium, bilirubin, inorganic phosphate, total protein, albumin, and globulin, were identical, and those of urea, creatinine, cholesterol, uric acid, calcium, and alkaline phosphatase were higher than those considered normal in younger people. Sex differences were demonstrable for serum urea, creatinine, bilirubin, phosphate, cholesterol, calcium, and alkaline phosphatase; in the last four instances these seemed likely to be of clinical importance. [ABSTRACT FROM PUBLISHER]