SC411 treatment can enhance survival in a mouse model of sickle cell disease.

Sickle cell disease (SCD) is one of the most common inherited blood disorder among African Americans affecting 70,000-100,000 individuals in the United States. It is characterized by abnormal hemoglobin (HbS) which develops into severe hemolytic anemia and vaso-occlusive crisis. Therefore, patients with SCD suffer from a chronic state of inflammation, which is responsible for multiple organ damage, ischemic attacks, and premature death. Another major hallmark of SCD patients is the abnormally low levels of omega-3 fatty acids, especially docosahexaenoic acid (DHA) in their red blood cell membranes. Treatment with DHA can reduce red blood cell adhesion and enhance cerebral blood flow, thus, our main goal is to investigate the effect of SC411, which is a novel, highly purified DHA ethyl ester formulation with a proprietary delivery platform in SCD. Utilizing a transgenic mouse model of SCD (HbSS-Townes) and recurrent hypoxic challenges (10%O2, 0.5% CO2 and balance N2 for 3 h) to mimic ischemic-like conditions, our data suggest that SC411 can elevate blood DHA and eicosapentaenoic acid (EPA) levels after 8 weeks of treatment. SC411 can also decrease arachidonic acid (AA) and sickling of red blood cells. In addition, SC411-treated SCD mice showed presented with cerebral blood flow, alleviated neuroinflammation, and revived working memory which ultimately enhanced overall survival. In summary, this study suggests that treatment with SC411 improves cellular and functional outcomes in SCD mice. This finding may provide novel therapeutic opportunities in the treatment against ischemic injury elicited by SCD.

Psammomatous Cavernous Malformation Presenting as Drug-Resistant Epilepsy: Case Illustration and Review of Literature.

BACKGROUND: Psammoma bodies (PBs) are whorled, laminated hyaline spherules containing calcium deposits. Intracranially, the presence of PBs is associated with variants of meningioma and pituitary lesions, as well as aging choroid plexus. Limited information exists on their presence in vascular malformation. RESULTS: In this report, we describe a case of an adolescent male with drug-resistant epilepsy that was surgically managed at our regional epilepsy center. The epileptogenic focus was determined to be emanating from an indolent right insular lesion. Histopathologic evaluation showed the abundance of intravascular and perivascular PBs. Immunohistochemical evaluation confirmed the vascular origin using vascular markers. The unusual presence of PBs in a vascular lesion was unanticipated. CONCLUSIONS: Based on our case, we present the clinicoradiologic characteristics, supplemented with intraoperative findings, for this unusual lesion. In addition, because of the unusual presence of PBs in vascular lesions, we provide the findings of a systematic literature review to show the association of PBs with intracranial vascular lesions.

Effect of magnesium supplementation on carotid intima-media thickness and flow-mediated dilatation among hemodialysis patients: a double-blind, randomized, placebo-controlled trial.

OBJECTIVES: The aim of the present study was to determine the efficacy of oral magnesium (Mg) supplementation on endothelial function through evaluation of carotid intima-media thickness (cIMT), brachial artery flow-mediated dilatation (FMD), and C-reactive protein (CRP) among hemodialysis (HD) patients. METHODS: This randomized, controlled, double-blind clinical trial consisted of 54 patients on HD. One group was treated orally with 440 mg of Mg oxide 3 times per week for 6 months (n = 29). The control group (n = 25) was given placebo using the same administration protocol. cIMT, FMD, serum calcium levels, phosphorus, lipid, CRP, and bicarbonate were measured at baseline and at 6 months in both groups. RESULTS: At 6 months, cIMT was significantly decreased in the Mg group (0.84 ± 0.13 mm at baseline and 0.76 ± 0.13 mm at 6 months, p = 0.001). However, in the placebo group, cIMT was significantly increased (0.73 ± 0.13 and 0.79 ± 0.12 mm, respectively, p = 0.003). When hypertension, diabetes mellitus, smoking, hyperlipidemia, and systemic lupus erythematosus were controlled for in the analysis, the effect of Mg remained significant in both groups (p = 0.000). CONCLUSION: Our results indicate that Mg might not improve endothelial function (CRP level and FMD) and that a decreased cIMT as a marker of atherosclerosis may be due to the inhibition of calcification through the regulation parathormone, calcium, and phosphorus.

The thalamus and multiple sclerosis: modern views on pathologic, imaging, and clinical aspects.

The paired thalamic nuclei are gray matter (GM) structures on both sides of the third ventricle that play major roles in cortical activation, relaying sensory information to the higher cortical centers that influence cognition. Multiple sclerosis (MS) is an immune-mediated disease of the human CNS that affects both the white matter (WM) and GM. A number of clinical observations as well as recent neuropathologic and neuroimaging studies have clearly demonstrated extensive involvement of the thalamus, basal ganglia, and neocortex in patients with MS. Modern MRI techniques permit visualization of GM lesions and measurement of atrophy. These contemporary methods have fundamentally altered our understanding of the pathophysiologic nature of MS. Evidence confirms the contention that GM injury can be detected in the earliest phases of MS, and that iron deposition and atrophy of deep gray nuclei are closely related to the magnitude of inflammation. Extensive involvement of GM, and particularly of the thalamus, is associated with a wide range of clinical manifestations including cognitive decline, motor deficits, fatigue, painful syndromes, and ocular motility disturbances in patients with MS. In this review, we characterize the neuropathologic, neuroimaging, and clinical features of thalamic involvement in MS. Further, we underscore the contention that neuropathologic and neuroimaging correlative investigations of thalamic derangements in MS may elucidate not heretofore considered pathobiological underpinnings germane to understanding the ontogeny, magnitude, and progression of the disease process.

Preventive effect of vitamin D3 supplementation on conversion of optic neuritis to clinically definite multiple sclerosis: a double blind, randomized, placebo-controlled pilot clinical trial.

Multiple sclerosis (MS) presents with optic neuritis (ON) in 20 % of cases and 50 % of ON patients develop MS within 15 years. In this study, we evaluated the preventive effects of vitamin D3 administration on the conversion of ON to MS (primary outcome) and on the MRI lesions (secondary outcome) of ON patients with low serum 25 (OH) D levels. Thirty ON patients (15 in each of 2 groups, aged 20-40 years) with serum 25 (OH) D levels of less than 30 ng/ml were enrolled in a double blind, randomized, parallel-group trial. The treatment group (cases) received 50,000 IU of vitamin D3 weekly for 12 months and the control group (controls) received a placebo weekly for 12 months. Finally, the subsequent relapse rate and changes in MRI plaques were compared between the two groups. Risk reduction was 68.4 % for the primary outcome in the treatment group (relative risk = 0.316, p = 0.007). After 12 months, patients in the treatment group had a significantly lower incidence rate of cortical, juxtacortical, corpus callosal, new T2, new gadolinium-enhancing lesions and black holes. The mean number of total plaques showed a marginally significant decrease in the group receiving vitamin D3 supplementation as compared with the placebo group (p = 0.092). Administration of vitamin D3 supplements to ON patients with low serum vitamin 25 (OH) D levels may delay the onset of a second clinical attack and the subsequent conversion to MS.

Vitamin D and multiple sclerosis: a critical review and recommendations on treatment.

Multiple sclerosis (MS) is an immune-mediated and degenerative disease of nervous system, which affects mostly young adults. Vitamin D deficiency is a well-known environmental risk factor for MS and is considerable in terms of immediate clinical implications. In addition to its classical action on regulation of bone homeostasis, vitamin D may have a potent impact on cytokine profiles and neuro-inflammation. Given the immunomodulatory effects of vitamin D and its high rate of deficiency in MS patients, prescribing vitamin D is a remarkable issue in MS. The results from several experimental and clinical studies indicate that vitamin D supplementation may ameliorate the inflammation during the relapse phase and attenuate disease progression. We present the experimental and clinical studies, which assessed the effects of vitamin D on the pathophysiology, prevalence and management of MS. The authors also discuss current recommendations on prescription of this vitamin to MS patients.

Molecular epigenetics, chromatin, and NeuroAIDS/HIV: translational implications.

We describe current research that applies epigenetics to a novel understanding of the immuno-neuropathogenesis of HIV-1 viral infection and NeuroAIDS. We propose the hypothesis that HIV-1 alters the structure-function relationship of chromatin, coding DNA and non-coding DNA, including RNA transcribed from these regions resulting in pathogenesis in AIDS, drug abuse, and NeuroAIDS. We discuss the general implications of molecular epigenetics with special emphasis on drug abuse, bar-codes, pyknons, and miRNAs for translational and clinical research. We discuss the application of the recent recursive algorithm of biology to this field and propose to synthesize the Genomic and Epigenomic views into a holistic approach of HoloGenomics.

Combination therapy with interferon beta-1a and doxycycline in multiple sclerosis: an open-label trial.

OBJECTIVE: To evaluate the efficacy, safety, and tolerability of combination therapy with intramuscular interferon beta-1a and oral doxycycline, a potent inhibitor of matrix metalloproteinases, in patients with relapsing-remitting multiple sclerosis (RRMS) having breakthrough disease activity. DESIGN: Open-label, 7-month trial. SETTING: Louisiana State University Health Sciences Center, Shreveport. PATIENTS: Fifteen patients with RRMS taking interferon beta-1a with breakthrough disease activity took doxycycline for 4 months. Patients underwent monthly neurologic examination, magnetic resonance imaging of the brain using triple-dose gadolinium, and safety blood work. INTERVENTIONS: Ongoing treatment with intramuscular interferon beta-1a plus oral doxycycline, 100 mg daily, for 4 months. MAIN OUTCOME MEASURES: The primary end point was gadolinium-enhancing lesion number change, and the secondary end points were relapse rates, safety and tolerability of the combination of interferon beta-1a and doxycycline in patients with MS, Expanded Disability Status Scale score, serum matrix metalloproteinase-9 levels, and transendothelial migration of monocytes exposed to serum from patients with RRMS. RESULTS: Combination of doxycycline and interferon beta-1a treatment resulted in reductions in contrast-enhancing lesion numbers and posttreatment Expanded Disability Status Scale values (P < .001 for both). Only 1 patient relapsed. Multivariate analyses indicated correlations between decreased serum matrix metalloproteinase-9 levels and enhancing lesion activity reduction. Transendothelial migration of monocytes incubated with serum from patients with RRMS undergoing combination therapy was suppressed. Adverse effects were mild; no adverse synergistic effects of combination therapy or unexpected adverse events were reported. CONCLUSIONS: Combination of intramuscular interferon beta-1a and oral doxycycline treatment was effective, safe, and well tolerated. Controlled clinical trials in larger cohorts of patients with MS are needed to evaluate the efficacy and tolerability of this combination. Trial Registration clinicaltrials.gov Identifier: NCT00246324

Acupuncture therapy for the symptoms of Parkinson's disease.

Interest in alternative medical treatments, including acupuncture, is increasing. Alternative treatments must be subjected to the same objective standards as all medical treatments. A non-blinded pilot study of the safety, tolerability, and efficacy of acupuncture (ACUPX) for the symptoms of (PD) was performed. Twenty PD patients (mean age, 68 years; disease duration, 8.5 years; Hoehn and Yahr [H&Y] stage, 2.2; Unified Parkinson's Disease Rating Scale score [UPDRS], 38.7) each received acupuncture treatments by a licensed acupuncturist. All patients were treated with two acupuncture treatment sessions per week. The first seven patients received 10 treatments and the last 13 patients 16 treatments. Patients were evaluated before and after ACUPX with the Sickness Impact Profile (SIP); UPDRS; H & Y; Schwab and England (S & E); Beck Anxiety Inventory (BAI); Beck Depression Inventory (BDI); quantitative motor tests, including timed evaluations of arm pronation supination movements, finger dexterity, finger movements between two fixed measured points, and the stand-walk-sit test; and a patient questionnaire designed for the study. Following ACUPX, there were no significant changes in the UPDRS, H&Y, S&E, BAI, BDI, quantitative motor tests, total SIP or the two SIP Dimension scores. Analysis of the 12 SIP categories not corrected for multiple comparisons revealed a post-ACUPX improvement in the sleep and rest category only (P = 0.03). On the patient questionnaire, 85% of patients reported subjective improvement of individual symptoms including tremor, walking, handwriting, slowness, pain, sleep, depression, and anxiety. There were no adverse effects. ACUPX therapy is safe and well tolerated in PD patients. A range of PD and behavioral scales failed to show improvement following ACUPX other than sleep benefit, although patients reported other discrete symptomatic improvements. A broad battery of tests in PD patients suggested that ACUPX resulted in improvement of sleep and rest only. This finding needs to be verified using more in-depth and controlled evaluation of ACUPX for PD-related sleep disturbance.