Non-glycosylated BMP-2 can induce ectopic bone formation at lower concentrations compared to glycosylated BMP-2.

Bone morphogenic protein-2 (BMP-2) is a well-known growth factor that can improve the biological performance of bone substitute materials. BMP-2 produced via bacterial expression systems are non-glycosylated (ng) whereas native and recombinant equivalents produced in mammalian cell expression systems are glycosylated (g) proteins. ngBMP-2 is less soluble, resulting in lower BMP-2 release from carriers as used as bone substitute materials. This seems promising for reducing the amount of included growth factor in bone substitute materials. Hence, it was hypothesized that ngBMP-2 would induce formation of the same amount of bone at an ectopic site at lower dosage as gBMP-2. To that end, gBMP-2 and ngBMP-2 were firstly in vitro comparatively evaluated for biological activity and release from a calcium phosphate (CaP) based bone substitute material. Thereafter, an ectopic implantation model in rats was used, in which gBMP-2 and ngBMP2 were loaded in various dosages (2-20 µg/implant) on the CaP-based bone substitute material and implanted for 4 and 12 weeks. The results revealed that both the in vitro biological activity of and the in vitro release of ngBMP-2 are lower compared to gBMP2. Upon ectopic implantation, however, ngBMP-2 loaded implants induced more bone formation at lower concentrations from 4-weeks onward compared to gBMP-2 equivalents, indicating the value of ngBMP-2 as a potential alternative for mammalian produced recombinant BMP-2 for bone regenerative therapies.

Experimental study of radioimmunotherapy versus chemotherapy for colorectal cancer.

BACKGROUND: Radioimmunotherapy (RIT) has been shown to reduce the incidence of local recurrence of colorectal cancer in an experimental model. The aim of the present study was to investigate the survival benefit of RIT compared with chemotherapy. METHODS: An anastomosis was constructed in male Wag/Rij rats after intraluminal injection of CC531 tumour cells. The therapeutic efficacy of (177) Lu-labelled MG1 (single intravenous dose of 300 MBq/kg, n = 20) was compared with that of 5-fluorouracil-based chemotherapy (6 weekly cycles administered intraperitoneally, n = 20) and no treatment (n = 20). The primary endpoint was survival. Toxicity was monitored by bodyweight measurement. RESULTS: Both chemotherapy and RIT affected bodyweight, but the weight of animals in the RIT group remained significantly higher than in the chemotherapy group (median slope of bodyweight plot 0·48 versus 0·30 g/day; P < 0·001). Kaplan-Meier analysis showed that overall survival in the RIT and chemotherapy groups was significantly better than that in the control group (50 and 46 per cent versus 25 per cent respectively after 170 days; P = 0·024 and P = 0·029). Survival after treatment with RIT did not differ from that after chemotherapy (P = 0·911). CONCLUSION: RIT is as effective as chemotherapy in experimental colorectal cancer.

Correlation of impedance response patterns to histological findings in irritant skin reactions induced by various surfactants.

We have explored the use of measurements of electrical impedance to discriminate between the effects of different irritant substances upon the skin, and have studied the relationships between impedance and histopathological change. Three compounds with different chemical profiles were tested on volunteers: sodium lauryl sulphate, benzalkonium chloride and nonanoic acid. The concentrations selected were such that each irritant produced responses of a similar order, as judged by visual scores. The magnitude and phase of electrical impedance were measured and, for comparison, also the transepidermal water loss. Four physically distinct aspects (indices) were devised from the impedance data, and the values obtained were statistically analysed. The three irritants produced different effects, giving distinctive impedance patterns. These were also found to be reflected by three different types of histopathological skin response. Our results suggest that the indices can be used to classify irritant contact reactions, which it is difficult or impossible to achieve by other non-invasive techniques.

Electrical impedance measured to five skin depths in mild irritant dermatitis induced by sodium lauryl sulphate.

The non-invasive electrical impedance technique used in this study reflects structural changes in a tissue, and provides an estimate of the level of oedema by a simple impedance index. Sodium lauryl sulphate (SLS), dissolved in water at concentrations of 0.1, 0.5 and 2.0%, was applied for 24 h in 12 mm Finn chambers on both volar forearms of 12 healthy volunteers. An unoccluded area was used as a reference site. Readings from all sites were taken before the application of the irritant, and 24 h after its removal. After the last reading, a 3-mm punch biopsy was taken from each test site for histological examination. The results obtained from electrical impedance measurements at five different skin depths were correlated with those obtained from histological examination, visual scoring and transepidermal water loss (TEWL). For all of the methods used the responses were proportional to the concentration of the irritant. Statistically significant changes of electrical impedance were found for all depths and concentrations, except for 0.1% SLS at the most superficial depth. The histological changes were focused in the epidermis, and mainly consisted of oedema. Alterations in the thickness of the epidermis due to oedema were used as a quantitative parameter for correlation with the assessment of irritation using the electrical impedance technique. For the detection of irritant reactions, TEWL and electrical impedance are more sensitive than visual scoring, and selection of the optimum depth penetration further increases the sensitivity of the electrical impedance measurement.

Electrical impedance for estimation of irritation in oral mucosa and skin.

Our aim is to establish an objective, easy-to-use technique to evaluate tissue irritation in vivo using non-invasive electrical impedance measurements. Such a technique would facilitate testing the biocompatibility of various materials, and also in quantifying skin diseases and other processes involving structural changes. It has been found that irritation of the oral mucosa not clinically or histologically discernible could be detected with a simple device based on electrical impedance techniques. Originally, the key problem was to focus the probing electrical field in order to minimize artefacts emanating from tissue layers of no interest. The device was then refined and applied to skin testing. It was found that irritation effects far below the limit of the commonly used visual readings could be detected. In this case, it is desirable to exclude from the measurement tissue layers with no diagnostic information, or at least reduce their influence. In this paper, the essential steps of the development of a multi-frequency depth selective device are reviewed.

[Dementia in the elderly. A 3-year project]. / Demenstilstander hos eldre. Et treårig pilotprosjekt.

In order to meet the need of proper examination and treatment of memory problems in the elderly a specialized unit of psychogeriatrics has been established as a pilot project. In the period from September 1986 to April 1988, 146 persons were examined, 42% as outpatients and 58% as inpatients. The average age was 75.3 years. 54% had dementia senilis and 16% other sorts of dementia. 30% were not demented: 14% had a psychiatric illness, 8% organic damage or illness of the brain and 7% were confused. Overdose or wrong use of psychopharmacological drugs was a frequent problem, and cutting out the medication, regulating the dose, or changing to another medicine had surprising consequences. The further treatment was planned in cooperation with the patient's family and the community health service. A follow-up after nine months indicated that this was a positive procedure for the patients, and that the unit was a professional resource to the local health services in the whole district. The hospital has now been allocated funds from the Government to function as a competence centre for part of Eastern Norway.