Multicentre, randomised, double blind, placebo controlled, phase III study of weekly, low dose, subcutaneous interferon beta-1a in secondary progressive multiple sclerosis.

Objective: Interferon (IFN) beta has repeatedly shown benefit in multiple sclerosis (MS) in reducing the rate of relapse, the disease activity as shown with magnetic resonance imaging and, to some degree, the progression of disability; however, it is unknown how much the therapeutic response depends on the dose, the subgroup involved, and the disease stage. This multicentre, double blind, placebo controlled study explored the dose–response curve by examining the clinical benefit of low dose IFN beta-1a (Rebif®), 22 µg subcutaneously once weekly, in patients with secondary progressive MS. Methods: A total of 371 patients with clinically definite SPMS were randomised to receive either placebo or subcutaneous IFN beta-1a, 22 µg once weekly, for 3 years. Clinical assessments were performed every 6 months. The primary outcome was time to sustained disability, as defined by time to first confirmed 1.0 point increase on the Expanded Disability Status Scale (EDSS). Secondary outcomes included a sensitive disability measure and relapse rate. Results: Treatment had no beneficial effect on time to confirmed progression on either the EDSS (hazard ratio (HR) = 1.13; 95% confidence interval (CI) 0.82 to 1.57; p = 0.45 for 22 µg v placebo) or the Regional Functional Status Scale (HR = 0.93; 95% CI 0.68 to 1.28; p = 0.67). Other disability measures were also not significantly affected by treatment. Annual relapse rate was 0.27 with placebo and 0.25 with IFN (rate ratio = 0.90; 95% CI 0.64 to 1.27; p = 0.55). The drug was well tolerated with no new safety concerns identified. No significant gender differences were noted. Conclusions: This patient population was less clinically active than SPMS populations studied in other trials. Treatment with low dose, IFN beta-1a (Rebif®) once weekly did not show any benefit in this study for either disability or relapse outcomes, including a subgroup with preceding relapses. These results add a point at one extreme of the dose–response spectrum of IFN beta therapy in MS, indicating that relapses in this phase may need treatment with higher doses than in the initial phases

Safety and efficacy of cladribine tablets in patients with relapsing-remitting multiple sclerosis: Results from the randomized extension trial of the CLARITY study.

BACKGROUND: In the 2-year CLARITY study, cladribine tablets significantly improved clinical and magnetic resonance imaging (MRI) outcomes (vs placebo) in patients with relapsing-remitting multiple sclerosis (MS). OBJECTIVE: To assess the safety and efficacy of cladribine treatment in a 2-year Extension study. METHODS: In this 2-year Extension study, placebo recipients from CLARITY received cladribine 3.5 mg/kg; cladribine recipients were re-randomized 2:1 to cladribine 3.5 mg/kg or placebo, with blind maintained. RESULTS: A total of 806 patients were assigned to treatment. Adverse event rates were generally similar between groups, but lymphopenia Grade ⩾ 3 rates were higher with cladribine than placebo (Grade 4 lymphopenia occurred infrequently). In patients receiving cladribine 3.5 mg/kg in CLARITY and experiencing lymphopenia Grade ⩾ 3 in the Extension, >90% of those treated with cladribine 3.5 mg/kg and all treated with placebo in the Extension, recovered to Grade 0-1 by study end. Cladribine treatment in CLARITY produced efficacy improvements that were maintained in patients treated with placebo in the Extension; in patients treated with cladribine 3.5 mg/kg in CLARITY, approximately 75% remained relapse-free when given placebo during the Extension. CONCLUSION: Cladribine tablets treatment for 2 years followed by 2 years' placebo treatment produced durable clinical benefits similar to 4 years of cladribine treatment with a low risk of severe lymphopenia or clinical worsening. No clinical improvement in efficacy was apparent following further treatment with cladribine tablets after the initial 2-year treatment period in this trial setting.This study was sponsored by EMD Serono, Inc., a business of Merck KGaA, Darmstadt, Germany (in the United States), and Merck Serono SA, Geneva, an affiliate of Merck KGaA Darmstadt, Germany (rest of the world)

Determination of the Wound Healing Potentials of Medicinal Plants Historically Used in Ghana

The present study was carried out to investigate the wound healing potentials of 17 medicinal plants historically used in Ghana for wound healing. Warm and cold water extracts were prepared from the 17 dried plant species and tested in vitro in the scratch assay with NIH 3T3 fibroblasts from mice. The wound healing scratch assay was used to evaluate the effect of the plants on cell proliferation and/or migration in vitro, as a test for potential wound healing properties. After 21 hours of incubation increased proliferation and/or migration of fibroblasts in the scratch assay was obtained for 5 out of the 17 plant species. HPLC separation of the most active plant extract, which was a warm water extract of Philenoptera cyanescens, revealed the wound healing activity to be attributed to rutin and a triglycoside of quercetin. The present study suggests that Allophylus spicatus, Philenoptera cyanescens, Melanthera scandens, Ocimum gratissimum, and Jasminum dichotomum have wound healing activity in vitro

Determination of the Wound Healing Potentials of Medicinal Plants Historically Used in Ghana

The present study was carried out to investigate the wound healing potentials of 17 medicinal plants historically used in Ghana for wound healing. Warm and cold water extracts were prepared from the 17 dried plant species and tested in vitro in the scratch assay with NIH 3T3 fibroblasts from mice. The wound healing scratch assay was used to evaluate the effect of the plants on cell proliferation and/or migration in vitro, as a test for potential wound healing properties. After 21 hours of incubation increased proliferation and/or migration of fibroblasts in the scratch assay was obtained for 5 out of the 17 plant species. HPLC separation of the most active plant extract, which was a warm water extract of Philenoptera cyanescens, revealed the wound healing activity to be attributed to rutin and a triglycoside of quercetin. The present study suggests that Allophylus spicatus, Philenoptera cyanescens, Melanthera scandens, Ocimum gratissimum, and Jasminum dichotomum have wound healing activity in vitro

Eliminating Medical Waste Liabilities Through Mobile Maceration and Disinfection

Commercial medical waste treatment technologies include incineration, melting, autoclaving, and chemical disinfection. Incineration disinfects, destroys the original nature of medical waste, and reduces the waste volume by converting organic waste content to carbon dioxide and water, leaving only residual inorganic ash. However, medical waste incinerator numbers have plummeted from almost 2,400 in 1995 to 115 in 2003 and to about 62 in 2005, due to negative public perception and escalating compliance costs associated with increasingly strict regulations. High-temperature electric melters have been designed and marketed as incinerator alternatives, but they are also costly and generally must comply with the same incinerator emissions regulations and permitting requirements. Autoclave processes disinfect medical waste at much lower operating temperatures than incinerators operate at, but are sometimes subject to limitations such as waste segregration requirements to be effective. Med-Shred, Inc. has developed a patented mobile shredding and chemical disinfecting process for on-site medical waste treatment. Medical waste is treated on-site at customer facilities by shredding and disinfecting the waste. The treated waste can then be transported in compliance with Health Insurance Portability and Accountability Act of 1996 (HIPAA) requirements to a landfill for disposal as solid municipal waste. A team of Idaho National Laboratory engineers evaluated the treatment process design. The process effectiveness has been demonstrated in mycobacterium tests performed by Analytical Services Incorporated. A process description and the technical and performance evaluation results are presented in the paper. A treatment demonstration and microbiological disinfecting tests show that the processor functions as it was intended

Preliminary physiologically based pharmacokinetic models for benzo[a]pyrene and dibenzo[def,p]chrysene in rodents

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental contaminants generated as byproducts of natural and anthropogenic combustion processes. Despite significant public health concern, physiologically based pharmacokinetic (PBPK) modeling efforts for PAHs have so far been limited to naphthalene, plus simpler PK models for pyrene, nitropyrene, and benzo[a]pyrene (B[a]P). The dearth of published models is due in part to the high lipophilicity, low volatility, and myriad metabolic pathways for PAHs, all of which present analytical and experimental challenges. Our research efforts have focused upon experimental approaches and initial development of PBPK models for the prototypic PAH, B[a]P, and the more potent, albeit less studied transplacental carcinogen, dibenzo[def,p]chrysene (DBC). For both compounds, model compartments included arterial and venous blood, flow limited lung, liver, richly perfused and poorly perfused tissues, diffusion limited fat, and a two compartment theoretical gut (for oral exposures). Hepatic and pulmonary metabolism was described for both compounds, as were fractional binding in blood and fecal clearance. Partition coefficients for parent PAH along with their diol and tetraol metabolites were estimated using published algorithms and verified experimentally for the hydroxylated metabolites. The preliminary PBPK models were able to describe many, but not all, of the available data sets, comprising multiple routes of exposure (oral, intravenous) and nominal doses spanning several orders of magnitude. Supported by Award Number P42 ES016465 from the National Institute of Environmental Health Sciences. Published by Elsevier Inc.Keywords: Metabolic activation, Gastrointestinal absorption, Cytochrome P450, Mouse skin, Benzo[a]Pyrene, Rat mammary gland, Ultimate carcinogens, Aromatic hydrocarbons, Tumor initiating activity, Partition coefficient

Cerebrospinal fluid biomarkers for predicting development of multiple sclerosis in acute optic neuritis: a population-based prospective cohort study

Background: Long-term outcome in multiple sclerosis (MS) depends on early treatment. In patients with acute optic neuritis (ON), an early inflammatory event, we investigated markers in cerebrospinal fluid (CSF), which may predict a diagnosis of MS. Methods: Forty patients with acute ON were recruited in a prospective population-based cohort with median 29 months (range 19–41) of follow-up. Paired CSF and serum samples were taken within 14 days (range 2–38), prior to treatment. Prospectively, 16/40 patients were by a uniform algorithm diagnosed with MS (MS-ON) and 24 patients continued to manifest isolated ON (ION) during follow-up. Levels of cytokines and neurofilament light chain (NF-L) were measured at the onset of acute ON and compared to healthy controls (HC). Significance levels were corrected for multiple comparisons (“q”). The predictive value of biomarkers was determined with multivariable prediction models using nomograms. Results: CSF TNF-α, IL-10, and CXCL13 levels were increased in MS-ON compared to those in ION patients (q = 0.021, 0.004, and 0.0006, respectively). MS-ON patients had increased CSF pleocytosis, IgG indices, and oligoclonal bands (OCBs) compared to ION (q = 0.0007, q = 0.0058, and q = 0.0021, respectively). CSF levels of IL-10, TNF-a, IL-17A, and CXCL13 in MS-ON patients correlated with leukocyte counts (r > 0.69 and p < 0.002) and IgG index (r > 0.55, p < 0.037). CSF NF-L levels were increased in ON patients compared to those in HC (q = 0.0077). In MS-ON, a progressive increase in NF-L levels was observed at 7 to 14 days after disease onset (r = 0.73, p < 0.0065). Receiver-operating characteristic (ROC) curves for two multivariable prediction models were generated, with IL-10, CXCL13, and NF-L in one (“candidate”) and IgG index, OCB, and leukocytes in another (“routine”). Area under the curve was 0.89 [95% CI 0.77–1] and 0.86 [0.74–0.98], respectively. Predictions of the risk of MS diagnosis were illustrated by two nomograms. Conclusions: CSF TNF-α, IL-10, CXCL13, and NF-L levels were associated with the development of MS, suggesting that the inflammatory and neurodegenerative processes occurred early. Based on subsequent diagnosis, we observed a high predictive value of routine and candidate biomarkers in CSF for the development of MS in acute ON. The nomogram predictions may be useful in the diagnostic work-up of MS

Hypericum sp.: essential oil composition and biological activities

Phytochemical composition of Hypericum genus has been investigated for many years. In the recent past, studies on the essential oils (EO) of this genus have been progressing and many of them have reported interesting biological activities. Variations in the EO composition of Hypericum species influenced by seasonal variation, geographic distribution, phenological cycle and type of the organ in which EO are produced and/or accumulated have also been reported. Although many reviews attributed to the characterization as well as biological activities of H. perforatum crude extracts have been published, no review has been published on the EO composition and biological activities of Hypericum species until recently (Crockett in Nat Prod Commun 5(9):1493–1506, 2010; Bertoli et al. in Global Sci Books 5:29–47, 2011). In this article, we summarize and update information regarding the composition and biological activities of Hypericum species EO. Based on experimental work carried out in our laboratory we also mention possible biotechnology approaches envisaging EO improvement of some species of the genus.Fundação para a Ciência e a Tecnologia (FCT) - project PTDC/AGR AAM/70418/2006, SFRH/BD/ 13283/2003

Longitudinal retinal changes in MOGAD

OBJECTIVE: Patients with myelin oligodendrocyte glycoprotein antibody (MOG-IgG) associated disease (MOGAD) suffer from severe optic neuritis (ON) leading to retinal neuro-axonal loss, which can be quantified by optical coherence tomography (OCT). We assessed whether ON-independent retinal atrophy can be detected in MOGAD. METHODS: Eighty MOGAD patients and 139 healthy controls (HC) were included. OCT data was acquired with 1) Spectralis spectral domain OCT (MOGAD (N=66) and HC (N=103)) and 2) Cirrus HD-OCT (MOGAD (N=14) and HC (N=36)). Macular combined ganglion cell and inner plexiform layer (GCIPL) and peripapillary retinal nerve fibre layer (pRNFL) were quantified. RESULTS: At baseline, GCIPL and pRNFL were lower in MOGAD eyes with a history of ON (MOGAD-ON) compared with MOGAD eyes without a history of ON (MOGAD-NON) and HC (p12 months ago (p<0.001). The overall MOGAD cohort did not exhibit faster GCIPL thinning compared with HC. INTERPRETATION: Our study suggests the absence of attack-independent retinal damage in MOGAD. Yet, ongoing neuroaxonal damage or oedema resolution seems to occur for up to 12 months after ON, which is longer than what has been reported with other ON forms. These findings support that the pathomechanisms underlying optic nerve involvement and the evolution of OCT retinal changes after ON is distinct in MOGAD. This article is protected by copyright. All rights reserved