Phenols and aromatic amines as thermal stabilizers in polyolefin processing

Scavenging of C- and O-centered free radicals is mandatory in processing stabilization of polypropylene. Phenolic antioxidants act principally as O-radical scavengers only. Aromatic amines, N,N'-disubstituted 1,4-phenylenediamines (PD) and 4,4'disubstituted diphenylamines (DPA), scavenge both C- and O-centered radicals and have consequently a broader activity spectrum. PD cannot be used, however, in polypropylene because of formation of strongly discoloring and staining sacrificial transformation products. Such products formed from DPA have even more discoloring properties. A good processing stability and acceptable extent of discoloration can be achieved by blends of phenols with 4,4'-di-tert.octyl DPA. The effect is considered as a beneficial cooperation between the two chain-breaking antioxidants involving interactions with amine-based transformation products.

Treatment of ocular allergies:nonpharmacologic, pharmacologic and immunotherapy

Ocular allergy is a significant and growing issue worldwide but for many patients, it is often not differentiated from systemic conditions, such as hay fever. Management of seasonal and perennial allergic conjunctivitis is often poor. Management is principally through avoidance measures (blocking or hygiene), nonpharmaceutical (such as artificial tears and cold compresses) and pharmaceutical (such as topical antihistamines and prophylactic mast cell stabilizers). Vernal and atopic keratoconjunctivitis are more severe and generally need treatment with NSAIDs, steroids and immunomodulators. Giant papillary conjunctivitis can be related to allergy but also is often contact lens related and in such cases can be managed by a period of abstinence and replacement of the lens or a change in lens material and/or design. Immunotherapy can be efficacious in severe, persistent cases of contact lens or allergic conjunctivitis.

Grewia polysaccharide gum as a pharmaceutical excipient

Grewia gum is obtained from the inner stem bark of the edible plant Grewia mollis Juss (Fam. Tiliaceae) which grows widely in the middle belt region of Nigeria, and is also cultivated. The dried and pulverised inner stem bark is used as a thickening agent in some food delicacies in that region of the country. This ability of the material to increase solution viscosity has generated a lot of interest and is the catalysing momentum for this research. Such materials have been used as stabilizers or suspending agents in cosmetics, foods and liquid medications, and as mucoadhesives and controlled release polymeric matrices in solid dosage forms. The physicochemical characterization of candidate excipients forms an essential step towards establishing suitability for pharmaceutical application. For natural gums, this usually requires isolation of the gum from the storage site by extraction processes. Grewia polysaccharide gum was extracted and dried using techniques such as air-drying, freeze-drying or spray-drying. Component analysis of the gum showed that it contains five neutral sugars: glucose, galactose, rhamnose, arabinose and xylose. The gum contains traces of elements such as zinc, magnesium, calcium and phosphorus. At low substance weight, the gum hydrates in aqueous medium swelling and dispersing to give a highly viscous dispersion with pseudoplasmic flow behaviour. The method by which drying is achieved can have significant effect on some physicochemical properties of the gum. Consequently, the intrinsic viscosity and molecular weight, and parameters of powder flow were shown to differ with the method of drying. The gum has good thermal stability. In comparison with established excipients, grewia gum may be preferable to gum Arabic or sodium carboxymethylcellulose as a suspending agent in ibuprofen suspension formulations. The release retardant property of the gum was superior to guar and Metolose® in ibuprofen matrices. Similarly, carboxy methylcellulose, Methocel®, gum Arabic or Metolose® may not be preferable to grewia gum when controlled release of a soluble drug like cimetidine is indicated. The mucoadhesive performance of the gum compared favourably with excellent mucoadhesives such as hydroxypropyl methylcellulose, carboxymethylcellulose, guar and carbopol 971 P.

The behaviour of antioxidants in polyolefins under conditions of U.V. exposure

The effects of antioxidants and stabilizers on the oxidative degradation of polyolefins (low density polyethylene [LDPE] and polypropylene [PPJ have been studied after subjecting to prior high temperature processing treatments. The changes in the both chemical and physical properties of unstabilized polymers occurring during processing were found to be strongly dependent on the amount of oxygen present in the mixer. Subsequent thermal and photo-oxidation showed very similar characteristics and the chromophore primarily responsible for:both thermo and photooxidative degradation of unstabilized polymers was found to be hydroperoxide formed during processing. Removal of hydroperoxide by heat treatment in an inert atmosphere although increasing ketonic carbonyl concentration, markedly decreased the rate of photo-oxidation, introducing an induction period similar to that of an unprocessed sample. It was concluded that hydroperoxides are the most important initiators in normally processed polymers during the early stages of photo-oxidation. Antioxidants such as metal dithiocarbamates which act by destroying peroxides into non-radica1 products were found to be efficient melt stabilizers for polyolefins and effective UV stabilizers during the initial photo-oxidation stage, whilst a phenolic antioxidant, n-octadecyl-3-(3',5'-di-terbutyl 4'hydroxypheny1) propionate (Irganox 1076) retarded photo-oxidation rate in the later stages. A typical 'UV absorber' 2-hydroxy-4-octyloxy-benzophenone (HOBP) has a minor thermal antioxidant action but retarded photo-oxidation at all stages. A substituated piperidine derivative, Bis [2.2.6.6-tetramethylpiperidlnyl-4] sebacate (Tinuvin 770) behaved as an pro-oxidant during thermal oxidation of polyolefins but was an effective stabilizer against UV light. The UV absorber, HOBP synergised effectively with both peroxide decomposing antioxidants (metal dithiocarbamates) and a chain-breaking antioxidant (Irganox 1076) during photo-oxidation of the poymers studed whereas the combined effect was additive during thermal oxidation. By contrast, the peroxide decornposers and chain-breaking antioxidant (Irganox 1076) which were effective synergists during thermal oxidation of LDPE· were antagonistic during photo-oxidation. The mechanisms of these processes are discussed.

Elevated left and reduced right orbitomedial prefrontal fractional anisotropy in adults with bipolar disorder revealed by tract-based spatial statistics

Context - Diffusion tensor imaging (DTI) studies in adults with bipolar disorder (BD) indicate altered white matter (WM) in the orbitomedial prefrontal cortex (OMPFC), potentially underlying abnormal prefrontal corticolimbic connectivity and mood dysregulation in BD. Objective - To use tract-based spatial statistics (TBSS) to examine WM skeleton (ie, the most compact whole-brain WM) in subjects with BD vs healthy control subjects. Design - Cross-sectional, case-control, whole-brain DTI using TBSS. Setting - University research institute. Participants - Fifty-six individuals, 31 having a DSM-IV diagnosis of BD type I (mean age, 35.9 years [age range, 24-52 years]) and 25 controls (mean age, 29.5 years [age range, 19-52 years]). Main Outcome Measures - Fractional anisotropy (FA) longitudinal and radial diffusivities in subjects with BD vs controls (covarying for age) and their relationships with clinical and demographic variables. Results - Subjects with BD vs controls had significantly greater FA (t > 3.0, P = .05 corrected) in the left uncinate fasciculus (reduced radial diffusivity distally and increased longitudinal diffusivity centrally), left optic radiation (increased longitudinal diffusivity), and right anterothalamic radiation (no significant diffusivity change). Subjects with BD vs controls had significantly reduced FA (t > 3.0, P = .05 corrected) in the right uncinate fasciculus (greater radial diffusivity). Among subjects with BD, significant negative correlations (P < .01) were found between age and FA in bilateral uncinate fasciculi and in the right anterothalamic radiation, as well as between medication load and FA in the left optic radiation. Decreased FA (P < .01) was observed in the left optic radiation and in the right anterothalamic radiation among subjects with BD taking vs those not taking mood stabilizers, as well as in the left optic radiation among depressed vs remitted subjects with BD. Subjects having BD with vs without lifetime alcohol or other drug abuse had significantly decreased FA in the left uncinate fasciculus. Conclusions - To our knowledge, this is the first study to use TBSS to examine WM in subjects with BD. Subjects with BD vs controls showed greater WM FA in the left OMPFC that diminished with age and with alcohol or other drug abuse, as well as reduced WM FA in the right OMPFC. Mood stabilizers and depressed episode reduced WM FA in left-sided sensory visual processing regions among subjects with BD. Abnormal right vs left asymmetry in FA in OMPFC WM among subjects with BD, likely reflecting increased proportions of left-sided longitudinally aligned and right-sided obliquely aligned myelinated fibers, may represent a biologic mechanism for mood dysregulation in BD.

The use of topiramate in mood stabilization

OBJECTIVE: To review data on the effectiveness of topiramate as a mood stabilizer. DATA SOURCES: Clinical literature accessed through MEDLINE (1985-September 2001) and the manufacturer. Key search terms included topiramate, mania, mood stabilizer, and bipolar disorder. DATA SYNTHESIS: The traditional standard therapy for bipolar disorder has been lithium. Other mood stabilizers are increasingly being used to manage this complex disorder. Studies that used topiramate in bipolar disorders were evaluated. CONCLUSIONS: The present data from open trials suggest that topiramate may possibly possess antimanic properties. Controlled, double-blind studies are required to confirm this efficacy

Gabapentin treatment for bipolar disorders

OBJECTIVE: To review the effectiveness data on the use of gabapentin in bipolar disorders. DATA SOURCES: Clinical literature was accessed through MEDLINE (January 1985–November 2000). Key search terms included gabapentin, mood stabilizer, and bipolar disorder. DATA SYNTHESIS: Bipolar disorder is a complex condition that can be difficult to treat effectively. Mood stabilizers are increasingly being used to manage bipolar disorder. Studies that used gabapentin in bipolar disorders are evaluated. CONCLUSIONS: From the data presented, gabapentin cannot be recommended for treatment of bipolar disorder. Further studies are required to determine whether gabapentin has any role in the management of bipolar disorder.