Nicotinamide downregulates gene expression of interleukin-6, interleukin-10, monocyte chemoattractant protein-1, and tumour necrosis factor-α gene expression in HaCaT keratinocytes after ultraviolet B irradiation.

Ultraviolet (UV) radiation has profound effects on human skin, causing sunburn, inflammation, cellular-tissue injury, cell death, and skin cancer. Most of these effects are mediated by a number of cytokines produced by keratinocytes. In this study we investigated whether nicotinamide (NCT), the amide form of vitamin B3, might have a protective function in reducing the expression of interleukin (IL)-1ß, IL-6, IL-8, IL-10, monocyte chemoattractant protein (MCP)-1 and tumour necrosis factor (TNF)-α in UV-irradiated keratinocytes. HaCaT cells were treated with UVB in the presence or absence of NCT, and cytokine mRNA levels were examined by quantitative real-time PCR. NCT significantly downregulated IL-6, IL-10, MCP-1 and TNF-α mRNA expression, whereas it did not exert any significant effect on IL-1ß or IL-8 expression. Because of its ability to decrease these cytokine mediators after UV exposure, NCT is a possible therapy to improve or prevent conditions induced or aggravated by UV light.

Modification of osteopontin and MMP-9 levels in patients with psoriasis on anti-TNF-α therapy.

Psoriasis is a chronic skin inflammatory disease in which a pleiotropic cytokine, tumor necrosis factor alpha (TNF-α), plays a central role, as demonstrated by the clinical success of anti-TNF-α therapy. Among the multiple effects of TNF-α on keratinocytes, the induction of matrix metalloproteinase-9 (MMP-9), a collagenase implicated in joint inflammation, might be one of the key mechanisms in psoriasis pathogenesis. Interestingly, MMP-9 expression can be enhanced also by osteopontin (OPN), a glycosylated protein whose levels are increased in skin and peripheral blood mononuclear cells (PBMC) of psoriasis patients. The aim of the current study is to investigate the relationship between OPN, MMP-9 and TNF-α in psoriasis. Our survey identified high levels of both OPN and MMP-9 in PBMC as well as skin of psoriatic patients with respect to healthy controls. Significant reduction of OPN and MMP-9 levels in PBMC, plasma and lesional skin of psoriasis patients was observed after 24 weeks of anti-TNF-α therapy. Moreover, OPN and MMP-9 were enhanced by TNF-α and down-regulated by anti-TNF-α treatment in healthy PBMC. These findings may suggest that OPN and MMP-9 may be regulated by TNF-α, indicating a possible role in the pathogenesis of psoriasis.

Cryptogenic stroke in hanging. A case report.

This paper reports the unique neuroimaging findings of a 37-year-old woman who attempted suicide by hanging. To our knowledge, this is the first reported case describing neuroimaging findings of unilateral lesions instead of the well-documented bilateral lesions after a hanging event. Computed tomography demonstrated a low density area in the right thalamus and no hemorrhage. 3.0 T Magnetic resonance revealed a hyperintense area on both T2-weighted and FLAIR images on the right thalamus. Diffusion weighted images demonstrated no area of diffusivity restriction. Another smaller lesion with the same signal characteristics was found in the left cerebellum. A second relevant point of this report is the observation that the most probable cause of the documented unilateral lesions was an ischemic-arterial event.

Silver syndrome variant of hereditary spastic paraplegia: A locus to 4p and allelism with SPG4.

OBJECTIVE: To perform a clinical and genetic study of two large Italian families (RM-36 and RM-51) showing the cardinal clinical features of Silver syndrome (SS), a rare dominantly inherited form of hereditary spastic paraplegia (HSP) complicated by amyotrophy of the small hand muscles. METHODS: Clinical assessment including neurophysiologic, neuropsychological, and neuroimaging evaluations. Genetic studies included linkage and sequence analyses. RESULTS: Using a genome-wide survey in the RM-36 family, a novel locus (SPG38) has been identified and mapped within the 13.1-cM region on chromosome 4p16-p15 between markers D4S432 and D4S1599. The RM-51 family was linked to the SPG4 locus at 2p21-p24 and sequence analysis of SPG4 showed a novel frameshift mutation p.Asp321GlyfsX6. Clinical examination of the affected members carrying the mutation showed high frequency of additional clinical features including decreased vibration sense, pes cavus, temporal lobe epilepsy, and cognitive impairment. CONCLUSIONS: This study demonstrates evidence of a novel locus SPG38 for Silver syndrome (SS) and suggests that genetic defects in SPG4 might lead to broad clinical features overlapped with those of SS.

Sixty-four-section CT cerebral perfusion evaluation in patients with carotid artery stenosis before and after stenting with a cerebral protection device.

BACKGROUND AND PURPOSE: Brain tissue viability depends on cerebral blood flow (CBF) that has to be kept within a narrow range to avoid the risk of developing ischemia. The aim of the study was to evaluate by 64-section CT (VCT) the cerebral perfusion modifications in patients with severe carotid stenosis before and after undergoing carotid artery stent placement (CAS) with a cerebral protection system. MATERIALS AND METHODS: Fifteen patients with unilateral internal carotid stenosis (>or=70%) underwent brain perfusional VCT (PVCT) 5 days before and 1 week after the stent-placement procedure. CBF and mean transit time (MTT) values were measured. RESULTS: Decreased CBF and increased MTT values were observed in the cerebral areas supplied by the stenotic artery as compared with the areas supplied by the contralateral patent artery (P < .001). A significant normalization of the perfusion parameters was observed after the stent-placement procedure (mean pretreatment MTT value, 5.3 +/- 0.2; mean posttreatment MTT value, 4.3 +/- 0.18, P < .001; mean pretreatment CBF value, 41.2 mL/s +/- 2.1; mean posttreatment CBF value, 47.9 mL/s +/- 2.9, P < .001). CONCLUSIONS: PVCT is a useful technique for the assessment of the hemodynamic modifications in patients with severe carotid stenosis. The quantitative evaluation of cerebral perfusion makes it a reliable tool for the follow-up of patients who undergo CAS.

A diffusion longitudinal MR imaging study in normal-appearing white matter in untreated relapsing-remitting multiple sclerosis.

BACKGROUND AND PURPOSE: Our aim was to evaluate the hypothesis that water diffusion alterations are present in normal-appearing white matter of patients with relapsing-remitting multiple sclerosis (RRMS) and to assess their change with time. MATERIALS AND METHODS: Fifty-four subjects with clinically diagnosed RRMS, with disease duration of less than 12 months and an expanded disability status scale (EDSS) score of <3.5, underwent a diffusion 3T MR imaging study. The apparent diffusion coefficient (ADC) maps generated were compared with those of 18 control subjects. Eighteen of the 54 patients underwent MR imaging assessment at 3 and 6 months after baseline evaluation. Remitting patients were clinically and MR imaging stable for the 2 months before the study. All patients were drug-free for the 3 months before the study, and in the relapsing patients, the MR imaging was always performed before beginning treatment. RESULTS: Mean ADC values showed significant differences when relapsing, remitting, and control patients were compared. The relapsing or remitting phase showed significant difference when compared both with controls (P < .01) and between them (P < .05). Comparing mean ADC values of patients with clinical disability (EDSS <2 versus EDSS >/=2) also provided significant differences with the control group (P < .01). The data of patients showing a relapsing episode during the longitudinal part of the study showed a significant difference compared with data from their remitting phase (P < .01). CONCLUSION: Brain microstructural changes can be detected and correlate with clinical impairment during the stages of MS. These changes modify with time in the relapsing group.

Evaluation of basal ganglia haemodynamic changes with perfusion-weighted magnetic resonance imaging in patients with Parkinson's disease.

PURPOSE: The aim of our study was to assess the regional cerebral blood flow (rCBF) of basal ganglia and thalami in patients with Parkinson's disease (PD) using perfusion-weighted magnetic resonance imaging (PW-MRI). MATERIAL AND METHODS: Twenty subjects affected by idiopathic PD according to the United Kingdom Brain Bank criteria were enrolled in the study. Twenty normal subjects matched for age and gender were included as controls. After 20-day therapy withdrawal, the PD patients underwent PW-MRI. The rCBF was calculated both in patients and in controls. The regions of interest were manually positioned on rCBF maps over the caudate nucleus, the putamen, the external and internal globus pallidus, and over the ventrolateral nucleus of the thalamus. Data were normalised with those obtained from parieto-occipital white matter (POWM). Statistical analysis was performed using a parametric ANOVA test. RESULTS: Patients showed a significant (p<0.01) interhemispheric asymmetry; rCBF values were higher on the more severely affected side. Controls showed no interhemispheric asymmetry. CONCLUSION: Our study suggests that PW-MRI is a valuable tool for assessing haemodynamic changes in PD patients. Haemodynamic change pattern may be useful in the early diagnosis of PD.

A new SPG4 mutation in a variant form of spastic paraplegia with congenital arachnoid cysts.

The clinical and genetic findings are described for 16 patients from a large Italian family with a variant form of hereditary spastic paraplegia and congenital arachnoid cysts inherited as an autosomal dominant trait. A molecular study has revealed a novel missense mutation, T614I, in exon 17 of SPG4, which may play a role in both focal cortical dysgenesis and neurodegeneration of the motor neurons in the corticospinal tract.