Obesity in psoriasis: leptin and resistin as mediators of cutaneous inflammation.

BACKGROUND: Obesity is a significant risk factor for psoriasis and body mass index (BMI) correlates with disease severity. Objectives To investigate the relationship between obesity and psoriasis, focusing on the role of adipokines such as leptin and resistin. PATIENTS/METHODS: Patients with psoriasis (n = 30) were recruited and their BMI, waist circumference and disease severity [Psoriasis Area and Severity Index (PASI)] were recorded. Fasting serum samples were obtained on enrolment and after a course of ultraviolet (UV) B treatment. Age-, sex- and BMI-matched healthy controls were also recruited. RESULTS: On enrolment, serum leptin and soluble leptin receptor levels were not raised compared with the controls. However, resistin, interleukin (IL)-1beta, IL-6, and chemokines CCL2, CXCL8 and CXCL9 were all significantly elevated in the patient group and serum resistin correlated with disease severity (r = 0.372, P = 0.043). Improvement after UVB treatment was accompanied by decreased serum CXCL8. In vitro, both leptin and resistin could induce CXCL8 and tumour necrosis factor-alpha production by blood monocytes, and leptin could additionally induce IL-1beta and IL-1 receptor antagonist production. Leptin also dose dependently increased secretion of the growth factor amphiregulin by ex vivo-cultured lesional psoriasis skin. CONCLUSIONS: These data support the view that leptin and resistin may be involved in the pathogenesis of psoriasis in overweight individuals, possibly by augmenting the cytokine expression by the inflammatory infiltrate.

Development and evaluation of microbicidal hydrogels containing monoglyceride as the active ingredient.

A number of medium-chain saturated and long-chain unsaturated fatty acids and their monoglycerides were tested against herpes simplex virus (HSV-1) to determine which lipids were most active during a short incubation time. The aim was to find which lipid would be preferable as the active ingredient in a virucidal hydrogel formulation for the purpose of preventing transmission of pathogens to mucosal membranes, particularly sexually transmitted viruses, such as herpes simplex virus and human immunodeficiency virus (HIV), and bacteria, such as Chlamydia trachomatis and Neisseria gonorrheae. The main strategy was that the formulations would be fast-acting, killing large numbers of virus or bacteria on contact in a short time, preferably causing at least a 10000-fold reduction in virus/bacteria titer in 1-5 min. Monocaprin, the 1-monoglyceride of capric acid, and lauric acid were found to be most active of all the lipids tested, causing a greater than 100000-fold reduction in virus titer in 1 min at a concentration of 20 mM. When tested at a concentration of 10 mM for 1 min, monocaprin was still fully active whereas lauric acid had no or negligible activity. It was concluded that monocaprin was most suitable as the active ingredient in a fast-acting virucidal gel formulation, and several hydrogel formulations containing monocaprin were tested. Formulations where the monoglyceride was dissolved in glycofurol were found to be active against HSV-1. The hydrogel formulations containing 20 mM monocaprin were highly virucidal in vitro and caused a greater than 100000-fold (HSV-1) inactivation of virus in human semen in 1 min. Formulations in dilution 1:10 were cytotoxic in monolayers of CV-1 cells, but they were 10-100 fold less cytotoxic than a commercial product which contains 2% nonoxynol-9.

Effects of footwear on measurements of balance and gait in women between the ages of 65 and 93 years.

BACKGROUND AND PURPOSE: Footwear is not consistently standardized in the administration of the Functional Reach Test (FRT), Timed Up & Go Test (TUG), and 10-Meter Walk Test (TMW). This study was conducted to determine whether footwear affected performance on these tests in older women. SUBJECTS: Thirty-five women, aged 65 to 93 years, were recruited from assisted living facilities and retirement communities. METHODS: Each subject performed the FRT, TUG, and TMW wearing walking shoes, wearing dress shoes, and barefooted. Because of space constraints at the facilities where the testing was performed, 22 subjects performed the FRT and TUG on a linoleum floor and 13 subjects performed the tests on a firm, low-pile, carpeted floor. All 35 subjects completed the TMW on a firm, low-pile, carpeted floor. One-way repeated-measures analyses of variance (ANOVAs) and a Tukey Honestly Significant Difference test were used to compare the outcomes for the 3 footwear conditions, with separate ANOVAs conducted for the different floor surfaces for the FRT and TUG. RESULTS: Subjects performed better on the FRT when barefooted or wearing walking shoes compared with when they wore dress shoes, regardless of floor surface. Differences were found among all footwear conditions for the TUG performed on the linoleum floor and for the TMW. For these tests, the women moved fastest in walking shoes, slower barefooted, and slowest wearing dress shoes. CONCLUSION AND DISCUSSION: Footwear should be documented and should remain constant from one test occasion to another when the FRT, TUG, and TMW are used in the clinic and in research. Footwear intervention may improve performance of balance and gait tasks in older women.

Quantitative assessment of the astrocytic response in natural scrapie of sheep.

Scrapie of sheep and goats belongs to the spongiform encephalopathies, a term derived from the characteristic vacuolar degeneration in the central nervous system. Astrocytosis has been described, but a systematic quantitative study has not been made. Such a study is important in resolving the still controversial issues as to whether the astrocytic response is caused directly by the infectious agent or represents a secondary reaction to tissue damage. In this study the numbers of astrocytes in 12 sheep with scrapie and 12 healthy sheep of a similar age were assessed and compared. Sections from eight planes of the brain were immunostained with anti-glial fibrillary acidic protein (GFAP) for astrocytes and their numbers counted in 40 areas of 1 mm2. The main findings were as follows. (1) A significant increase of astrocytes was detected in sheep with scrapie. (2) Astrocytosis was not usually related to the severity of the characteristic vacuolar lesions, indicating that it was at least partly due to a direct effect of the infectious agent but was not a secondary response to the neuronal damage. (3) The astrocytic response varied considerably between individual affected sheep; this may have been due to differences in agent strains, host response, or both.

Is there a need for special antenatal clinic for women with a medical disorder?

A two year review of clinical practice in a medical antenatal clinic was performed. Forty-six per cent of the patients were diabetics and the other 54% were a mixture of endocrine, cardiac, vascular and other medical disorders. The referral rate was 1.5% of total deliveries during the time period and the perinatal mortality rate was 27/1000. The preterm delivery rate was 20%. The feasibility of this kind of clinic in a single hospital is discussed.

Constitutive and visna virus induced expression of class I and II major histocompatibility complex antigens in the central nervous system of sheep and their role in the pathogenesis of visna lesions.

Expression of major histocompatibility complex (MHC) antigens was studied in the brains of 10 healthy sheep 2 months to 5 years old and 13 sheep infected with visna virus by intracerebral inoculation and killed one and 6 months post infection (p.i.). In healthy sheep there was prominent expression of class I, mainly on endothelial cells but also detected on ependyma, choroid plexus and in the leptomeninges. Class II expression was sparse. It was observed on perivascular cells, in choroid plexus, leptomeninges and on microglial cells in the white matter. No definite increase with age in the constitutive expression of class I and II was observed, confirming that we are dealing with a true constitutive expression. In visna-infected sheep a considerable induction of MHC antigens on microglia was observed, which correlated with severity of lesions and was mainly found in or adjacent to inflammatory infiltrates of the white matter. Increase in class II antigen expression was detected in all sheep but class I only in sheep with the most severe lesions 6 months p.i., an indication of a higher threshold for induction of class I than class II antigens on microglia. Few cells expressed viral antigens, indicating that direct immune-mediated destruction of infected cells plays a minor role in evolution of lesions. Since the preferential induction of MHC antigens on microglia in the white matter correlated with the lesion pattern, activated microglia may play a considerable role in the pathogenesis of lesions.

Biological and genetic differences between lung- and brain-derived isolates of maedi-visna virus.

During the epidemic caused by maedi-visna virus (MVV) of sheep in Iceland, the pulmonary affection, maedi, was the predominant clinical manifestation. In some flocks, however, a central nervous system (CNS) affection, visna, was the main cause of morbidity and mortality. As there is only one breed of sheep in the country, host factors did apparently not play an important role in the different clinical manifestations. To obtain some information on possible viral genetic determinants of neurotropism and neurovirulence we studied both phenotypic and genotypic properties of two maedi-visna virus strains; a strain that was originally isolated from the brain of sheep with encephalitis (visna), and another strain isolated from the lungs of a sheep suffering from pneumonia (maedi). The brain isolate was found to grow faster in sheep choroid plexus cells than the lung isolate, whereas the growth rate in macrophages was similar for the maedi and visna virus strains. Intracerebral inoculation indicated that the visna virus isolate induced more severe brain lesions than the maedi isolate. In addition, a pathogenic molecular clone derived from a visna strain (KV1772kv72/67) was tested for growth in sheep choroid plexus cells and macrophages. The molecularly cloned virus retained the fast growth rate in choroid plexus cells. The nucleotide sequence of the env gene and the U3 of the LTR was determined for the maedi strain and compared to that of the visna strains. There was an 11.7% difference in deduced amino acid sequence in the Env protein and a 6% difference in the LTR. The molecular clone KV1772kv72/67 will be a useful reagent for characterization of viral determinants of cell tropism in vitro and possibly neurovirulence in vivo.