The aim of this review article is to provide an overview of the role of pigs as a biomedical model for humans. The usefulness and limitations of porcine models have been discussed in terms of metabolic, cardiovascular, digestive and bone diseases in humans. Domestic pigs and minipigs are the main categories of pigs used as biomedical models. One drawback of minipigs is that they are in short supply and expensive compared with domestic pigs, which in contrast cost more to house, feed and medicate. Different porcine breeds show different responses to the induction of specific diseases. For example, ossabaw minipigs provide a better model than Yucatan for the metabolic syndrome as they exhibit obesity, insulin resistance and hypertension, all of which are absent in the Yucatan. Similar metabolic/physiological differences exist between domestic breeds (e.g. Meishan v. Pietrain). The modern commercial (e.g. Large White) domestic pig has been the preferred model for developmental programming due to the 2-to 3-fold variation in body weight among littermates providing a natural form of foetal growth retardation not observed in ancient (e.g. Meishan) domestic breeds. Pigs have been increasingly used to study chronic ischaemia, therapeutic angiogenesis, hypertrophic cardiomyopathy and abdominal aortic aneurysm as their coronary anatomy and physiology are similar to humans. Type 1 and II diabetes can be induced in swine using dietary regimes and/or administration of streptozotocin. Pigs are a good and extensively used model for specific nutritional studies as their protein and lipid metabolism is comparable with humans, although pigs are not as sensitive to protein restriction as rodents. Neonatal and weanling pigs have been used to examine the pathophysiology and prevention/treatment of microbial-associated diseases and immune system disorders. A porcine model mimicking various degrees of prematurity in infants receiving total parenteral nutrition has been established to investigate gut development, amino acid metabolism and non-alcoholic fatty liver disease. Endoscopic therapeutic methods for upper gastrointestinal tract bleeding are being developed. Bone remodelling cycle in pigs is histologically more similar to humans than that of rats or mice, and is used to examine the relationship between menopause and osteoporosis. Work has also been conducted on dental implants in pigs to consider loading; however with caution as porcine bone remodels slightly faster than human bone. We conclude that pigs are a valuable translational model to bridge the gap between classical rodent models and humans in developing new therapies to aid human health.

We examined the effect of route of delivery on brown adipose tissue (BAT) function and thermoregulation in lambs born either vaginally at term or by cesarean section close to term. Immediately after birth, lambs were placed in a warm (30 degrees C; WD) or cool (15 degrees C; CD) ambient temperature, and measurements of colonic temperature, plus heat production (i.e., oxygen consumption and carbon dioxide production), were recorded for 6 h. Over the first 30 min of life, colonic temperature remained constant in vaginally delivered lambs and was lower in the WD group. Following cesarean section delivery, colonic temperature declined rapidly, a response that was greater in the CD group. Cesarean section-delivered lambs had an increased reliance on shivering thermogenesis and restored colonic temperature after 2 h, and by 6 h these parameters were higher than in lambs born vaginally. Irrespective of delivery, temperature, plasma thyroid hormone concentrations and norepinephrine content of BAT were lower in lambs born by cesarean section compared with those born vaginally. Plasma cortisol concentrations and epinephrine content of BAT were greater in lambs born by cesarean section. The amount of uncoupling protein and level of guanosine 5'-diphosphate binding in BAT were higher in vaginally delivered than in cesarean section-delivered lambs, and for each group mean values were greater for CD than WD lambs. Cesarean section delivery results in altered thyroidal, adrenal, and sympathetic activity, which appears to have a marked influence on BAT function, thereby contributing to distinct differences in thermoregulation compared with lambs born vaginally.

SUMMARY1. This study examines the effect of chronic cold exposure during pregnancy, induced by winter shearing twin-bearing ewes 4 weeks before predicted lambing date, on 02 consumption and CO2 production during non-rapid-eye-movement (REM) sleep in lambs maintained for at least 1 h at warm (28-18 'C) and cold (14-5 'C) ambient temperatures at 1, 4, 14 and 30 days of age. This was combined with measurement of the thermogenic activity (GDP binding to uncoupling protein in mitochondrial preparations) of perirenal adipose tissue from lambs immediately after birth and at 33 days of age.2. Lambs born from shorn (cold-exposed) ewes were 15% heavier (P < 0-01) and possessed 21 % (P < 0-01) more perirenal adipose tissue that contained 40% more protein and mitochondrial protein than unshorn (P < 0-05) controls. Total GDP binding in perirenal adipose tissue was 40 % greater (P < 0'05) in lambs born from shorn ewes but there was no difference in lipid content of this tissue between the two groups.3. At 1 day of age, lambs born from shorn ewes exhibited a 16 % higher (P < 0 05) rate of 02 consumption (per kilogram bodyweight) at the warm temperature and a 40 % greater metabolic response to the cold ambient temperature. All lambs born from shorn ewes responded to cold exposure without shivering (i.e. via non-shivering thermogenesis) whilst shivering was measured in four out of seven lambs in the unshorn group. These differences had disappeared by 4 days of age as a result of a 25% increased (P < 0-01) rate of 02 consumption in the warm in lambs born from unshorn ewes and a 20 % decrease (P < 0 05) in the response to the cold in lambs from shorn ewes. Shivering during cold exposure was measured in six out of nine lambs born from shorn ewes indicating a rapid alteration in thermoregulatory responses to cold during the first few days of life.4. The levels of GDP binding and mitochondrial protein in perirenal adipose tissue fell by one-third in both groups of lambs during the first 33 days of life whereas lipid content either increased or was unchanged. This indicated that brown adipose tissue (BAT) was developing the characteristics of white adipose tissue. In lambs aged 33 days that were born from shorn ewes, perirenal adipose tissue weighed 88 % more MS 9883 M. E SYMONDS AND OTHERS (P < 0 01), contained more (P < 0 05) protein and lipid, and the level of total GDP binding to mitochondrial protein was 100 % greater than in lambs born from unshorn ewes. There were no differences at this age between the two groups of lambs in metabolic rate but four out of eight lambs born from shorn ewes exhibited shivering responses to a cold ambient temperature compared with seven out of eight in the unshorn group.5. It is concluded that maternal cold exposure during late pregnancy stimulates fetal growth and the thermogenic activity of BAT in the neonatal lamb. At 1 day of age this alternation in BAT was associated with an increased metabolic response to cold achieved entirely via non-shivering thermogenesis while longer term consequences...

No existing response measure independently predicts outcome. A complete response (TRG 1) defines a unique cohort after neoadjuvant therapy, associated closely with nodal response, and overall survival. This classification merits consideration for standardization of treatment response, and for inclusion in staging nomenclature.

We examined the effect of maternal chronic cold exposure, induced by winter-shearing ewes 4 weeks before their predicted lambing date, on brown adipose tissue (BAT) and liver development in lambs. Fetuses were sampled from under-fed (60% of energy requirements for maintenance and pregnancy of an unshorn ewe) shorn or unshorn ewes at 126,140 and 145 d of gestation. Lambs were sampled from ewes within 2 h of birth. Throughout gestation fetal body, BAT and liver weights were similar in shorn and unshorn groups. The level of GDP binding to mitochondrial uncoupling protein remained low throughout gestation, but increased dramatically after birth. Lambs born to shorn ewes possesd more mitochondrial protein and exhibited a significantly higher total thermogenic activity in BAT. Type I iodothyronine 5 deiodinas(EC 3.8.1.4) activity in BAT peaked at birth, as did hepatic iodothyronine Sdeiodinase activity and was significantly greater in lambs born to under-fed shorn ewes, which exhibited a higher plasma triiodothyronine concentration. Chronic maternal adaptations to prolonged cold exposure appear to enable pregnant ewes to compensate for the negative effects of under-feeding on fetal growth and development