Skeletal recovery after weaning does not require PTHrP

Mice lose 20% to 25% of trabecular bone mineral content (BMC) during lactation and restore it after weaning through unknown mechanisms. We found that tibial Pthrp mRNA expression was upregulated fivefold by 7 days after weaning versus end of lactation in wild‐type (WT) mice. To determine whether parathyroid hormone–related protein (PTHrP) stimulates bone formation after weaning, we studied a conditional knockout in which PTHrP is deleted from preosteoblasts and osteoblasts by collagen I promoter–driven Cre (Cre^ColI). These mice are osteopenic as adults but have normal serum calcium, calcitriol, and parathyroid hormone (PTH). Pairs of Pthrp^flox/flox;Cre^ColI (null) and WT;Cre^ColI (WT) females were mated and studied through pregnancy, lactation, and 3 weeks of postweaning recovery. By end of lactation, both genotypes lost lumbar spine BMC: WT declined by 20.6% ± 3.3%, and null decreased by 22.5% ± 3.5% (p < .0001 versus baseline; p = NS between genotypes). During postweaning recovery, both restored BMC to baseline: WT to –3.6% ± 3.7% and null to 0.3% ± 3.7% (p = NS versus baseline or between genotypes). Similar loss and full recovery of BMC were seen at the whole body and hind limb. Histomorphometry confirmed that nulls had lower bone mass at baseline and that this was equal to the value achieved after weaning. Osteocalcin, propeptide of type 1 collagen (P1NP), and deoxypyridinoline increased equally during recovery in WT and null mice; PTH decreased and calcitriol increased equally; serum calcium was unchanged. Urine calcium increased during recovery but remained no different between genotypes. Although osteoblast‐derived PTHrP is required to maintain adult bone mass and Pthrp mRNA upregulates in bone after weaning, it is not required for recovery of bone mass after lactation. The factors that stimulate postweaning bone formation remain unknown. © 2011 American Society for Bone and Mineral Research.     

Blood flow distribution in cerebral arteries

High-resolution phase–contrast magnetic resonance imaging can now assess flow in proximal and distal cerebral arteries. The aim of this study was to describe how total cerebral blood flow (tCBF) is distributed into the vascular tree with regard to age, sex and anatomic variations. Forty-nine healthy young (mean 25 years) and 45 elderly (mean 71 years) individuals were included. Blood flow rate (BFR) in 21 intra- and extracerebral arteries was measured. Total cerebral blood flow was defined as BFR in the internal carotid plus vertebral arteries and mean cerebral perfusion as tCBF/brain volume. Carotid/vertebral distribution was 72%/28% and was not related to age, sex, or brain volume. Total cerebral blood flow (717±123 mL/min) was distributed to each side as follows: middle cerebral artery (MCA), 21% distal MCA, 6% anterior cerebral artery (ACA), 12%, distal ACA, 4% ophthalmic artery, 2% posterior cerebral artery (PCA), 8% and 20% to basilar artery. Deviating distributions were observed in subjects with ‘fetal'' PCA. Blood flow rate in cerebral arteries decreased with increasing age (P<0.05) but not in extracerebral arteries. Mean cerebral perfusion was higher in women (women: 61±8; men: 55±6 mL/min/100 mL, P<0.001). The study describes a new method to outline the flow profile of the cerebral vascular tree, including reference values, and should be used for grading the collateral flow system.     

Atopy patch test reactions to Malassezia allergens differentiate subgroups of atopic dermatitis patients

BACKGROUND: The yeast Malassezia is considered to be one of the factors that can contribute to atopic dermatitis (AD). OBJECTIVES: To investigate the reactivity to Malassezia allergens, measured as specific serum IgE, positive skin prick test and positive atopy patch test (APT), in adult patients with AD. METHODS: In total, 132 adult patients with AD, 14 with seborrhoeic dermatitis (SD) and 33 healthy controls were investigated for their reactions to M. sympodialis extract and three recombinant Malassezia allergens (rMal s 1, rMal s 5 and rMal s 6). RESULTS: Sixty-seven per cent of the AD patients, but only one of the SD patients and none of the healthy controls, showed a positive reaction to at least one of the Malassezia allergens (extract and/or recombinant allergens) in at least one of the tests. The levels of M. sympodialis-specific IgE in serum correlated with the total serum IgE levels. Elevated serum levels of M. sympodialis-specific IgE were found in 55% and positive APT reactions in 41% of the AD patients with head and neck dermatitis. A relatively high proportion of patients without head and neck dermatitis and patients with low total serum IgE levels had a positive APT for M. sympodialis, despite lower proportions of individuals with M. sympodialis-specific IgE among these groups of patients. CONCLUSIONS: These results support that Malassezia can play a role in eliciting and maintaining eczema in patients with AD. The addition of an APT to the test battery used in this study reveals a previously overlooked impact of Malassezia hypersensitivity in certain subgroups of AD patients.     

The efficacy of nicotinamide gel 4% as an adjuvant therapy in the treatment of cutaneous erosions of pemphigus vulgaris

The high rate of morbidity and mortality resulting from long‐term use of corticosteroids in pemphigus vulgaris (PV) warrants discovery of a new treatment strategy. Based on the pathophysiology of PV, nicotinamide can block the process of blister formation through its anti‐inflammatory properties. This study was conducted to evaluate the clinical effectiveness of nicotinamide gel in the treatment of skin lesions of PV. In a double‐blind, placebo‐controlled study, eight PV patients with a total of 60 skin lesions were treated by either nicotinamide or placebo gel. After 30 days of treatment, epithelialization index of the two groups was compared. The mean of the epithelialization index in skin lesions that received nicotinamide was significantly higher than that of the placebo group (26 vs. –5.8, p < 0.001). Our results were suggestive that nicotinamide gel can effectively be used as an adjunctive treatment for PV lesions.