Ro 10–9359 is a retinoic acid derivative, selected for study because of a better tolerance than retinoic acid, shown in animal experiments. Doses of 25 mg b.i.d., 25 mg t.i.d. and 50 mg b.i.d. were administered orally to 27 patients suffering from severe chronic generalized psoriasis. The clinical efficacy was evaluated by means of a new index, psoriasis area and severity index (PASI) based on severity and area of psoriatic lesions. At doses of 25 mg t.i.d. or 50 mg b.i.d. Ro 10–9359 proved to be an extremely potent antipsoriatic drug. A more than 90% reduction of psoriatic lesions could be seen in 10 patients out of 20 after 4–8 weeks of treatment. This good effect lasted about 5 weeks after treatment. Side effects were frequent, but mostly mild and completely reversible after termination of treatment.

Sex differences in obesity-induced complications such as type 2 diabetes have been reported. The aim of the study was to pinpoint the mechanisms resulting in different outcome of female and male mice on a high-fat diet (HFD). Mice fed control or HFD were monitored for weight, blood glucose, and insulin for 14 weeks. Circulating chemokines, islet endocrine function and blood flow, as well as adipose tissue populations of macrophages and regulatory T-lymphocytes (Treg) were thereafter assessed. Despite similar weight (43.8±1.0 and 40.2±1.5 g, respectively), male but not female mice developed hyperinsulinemia on HFD as previously described (2.5±0.7 and 0.5±0.1 pmol/l, respectively) consistent with glucose intolerance. Male mice also exhibited hypertrophic islets with intact function in terms of insulin release and blood perfusion. Low-grade, systemic inflammation was absent in obese female but present in obese male mice (IL-6 and mKC, males: 77.4±17 and 1795±563; females: 14.6±4.9 and 240±22 pg/ml), and the population of inflammatory macrophages was increased in intra-abdominal adipose tissues of high-fat-fed male but not female mice. In contrast, the anti-inflammatory Treg cell population increased in the adipose tissue of female mice in response to weight gain, while the number decreased in high-fat-fed male mice. In conclusion, female mice are protected against HFD-induced metabolic changes while maintaining an anti-inflammatory environment in the intra-abdominal adipose tissue with expanded Treg cell population, whereas HFD-fed male mice develop adipose tissue inflammation, glucose intolerance, hyperinsulinemia, and islet hypertrophy.

No abstract

Drs Ioannidis and Trikalinos had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Drs van Meurs and Trikalinos contributed equally to this article.

Forty-eight community living women 66-87 years old volunteered to participate in a 12-month prospective, randomized, controlled, trial. The aim was to determine if a combined weight-bearing training program twice a week would be beneficial to bone mineral density and neuromuscular function. The participants were pairwise age-matched and randomly assigned to either an exercise group (n=24) or a control group (n=24). Twenty-one subjects in the intervention group and 19 in the control group completed the study. The exercise program lasted for 50 min and consisted of a combination of strengthening, aerobic, balance and coordination exercises. The mean percentage of scheduled sessions attended for the exercise group was 67%. At the completion of the study, the intervention group showed significant increments in bone mineral density of the Ward's triangle (8.4%, P<0.01) as well as improvement in maximum walking speed (11.4%, P<0.001) and isometric grip strength (9.9%, P<0.05), as compared to the control group. The conclusion was that a combined weight-bearing training program might reduce fracture risk factors by improving bone density as well as muscle strength and walking ability. This program could be suitable for older community living women in general, and might, therefore, have important implications for fracture prevention.

No abstract

OBJECTIVENo previous study has measured the oxygenation of intraportally transplanted islets, although recent data suggest that insufficient engraftment may result in hypoxia and loss of islet cells.RESEARCH DESIGN AND METHODSAfter intraportal infusion into syngeneic mice, islet oxygenation was investigated in 1-day-old, 1-month-old, or 3-month-old grafts and compared with renal subcapsular grafts and native islets. Animals received an intravenous injection of pimonidazole for immunohistochemical detection of low-oxygenated islet cells (pO2 <10 mmHg), and caspase-3 immunostaining was performed to assess apoptosis rates in adjacent tissue sections.RESULTSIn the native pancreas of nontransplanted animals, ∼30% of the islets stained positive for pimonidazole. In 1-day-old and 1-month-old grafts, the percentage of pimonidazole-positive islets in the liver was twice that of native islets, whereas this increase was abolished in 3-month-old grafts. Beneath the renal capsule, pimonidazole accumulation was, however, similar to native islets at all time points. Apoptosis rates were markedly increased in 1-day-old intrahepatic grafts compared with corresponding renal islet grafts, which were slightly increased compared with native islets. One month posttransplantation renal subcapsular grafts had similar frequencies of apoptosis as native islets, whereas apoptosis in intraportally implanted islets was still high. In the liver, islet graft vascular density increased between 1 and 3 months posttransplantation, and apoptosis rates simultaneously dropped to values similar to those observed in native islets.CONCLUSIONSThe vascular engraftment of intraportally transplanted islets is markedly delayed compared with renal islet grafts. The prolonged ischemia of intraportally transplanted islets may favor an alternative implantation site.

Background The number of hip fractures has doubled in the last 30–40 years in many countries. Age-adjusted incidence has been reported to be decreasing in Europe and North America, but is there a decreasing trend in all age groups?Patients and methods This population-based study included all hip-fracture patients over 50 years of age (a total of 2,919 individuals, 31% of whom were men) admitted to Umeå University Hospital, Sweden, from 1993 through 2005.Results The incidence of hip fracture declined between the periods 1993–1996 and 2001–2005: from 706 to 625 hip fractures per 105 women and from 390 to 317 hip fractures per 105 men. However, there was a 114% increase in the number of fractures in women aged 90 or older (12 and 25 hip fractures/year, respectively, in the two time periods). For the period 2001–05, women ≥ 90 years of age accounted for almost the same numbers of hip fractures as women aged 75–79 (27 fractures/year). The rate increased during this period, from 2,700 per 105 women to 3,900 per 105 women > 90 years. In men there were declining trends for both relative and absolute numbers.Interpretation Although age-adjusted incidence declined in the population > 50 years of age, absolute fracture rate and incidence increased in the very old. Women over 90 now have the same absolute number of hip fractures every year as women aged 75–79 years. There was a right-shift in hip fracture distribution towards the oldest old, probably due to an increased number of octo/nonagenarians, a new population of particularly frail old people that hardly existed earlier. Better health among septuagenarians may also have delayed the age at which fractures occurred. This changing pattern will strain orthopedic and geriatric resources even more.