Particle Morphology of Amorphous Aluminum Hydroxycarbonate and Its Effect on Tablet Production

The particle morphology of amorphous aluminum hydroxycarbonate was studied by disaggregation induced by phosphate adsorption and direct observation by high resolution transmission electron microscopy. The primary particles are sheet-like and have equivalent diameters of 55A or less. The primary particles are believed to correspond to planar polymers comprised of six-membered rings of aluminum ions joined by double hydroxide bridges. Secondary particles form by attractive interaction of primary particles. The size of the primary particles affects the porosity of the secondary particles. The granulating and tableting properties of two spray dried amorphous aluminum hydroxycarbonates were shown to be related to the size of the primary particles and the porosity of the secondary particles.     

Nicotine pharmacokinetics and subjective effects of three potential reduced exposure products, moist snuff and nicotine lozenge

Objective

To compare nicotine pharmacokinetics and subjective effects of three new smokeless tobacco potential reduced exposure products (PREPs; Ariva, Revel and Stonewall) with moist snuff (Copenhagen) and medicinal nicotine (Commit lozenge).

Methods

10 subjects completed a randomised, within‐subject, crossover study. Subjects used one product for 30 min at each of the five laboratory sessions. Maximal nicotine concentration (C_max) was determined and area under the concentration time curve (AUC) was calculated for a 90‐min period (during use and 60 min after use). Nicotine craving, withdrawal symptoms and ratings of product effects and liking were measured during product use.

Results

Nicotine AUC and C_max were higher for Copenhagen than for any other product (p<0.002) and higher for Commit than for either Ariva or Revel (p<0.001). C_max for Commit was also higher than for Stonewall (p = 0.03). Craving was lowest during use of Copenhagen (p<0.03). Craving during use of Stonewall, Ariva and Commit was lower than during use of Revel (p<0.05). Withdrawal symptom score during use of Copenhagen was lower than during use of Revel (p = 0.009). Copenhagen scores were higher (p<0.005) than all other products in several measures of drug effects and liking (feel good effects, satisfaction, liking and desire for product, and strength of product).

Conclusion

The new smokeless tobacco PREPs result in lower nicotine concentrations and equivalent or lower reductions in subjective measures compared with medicinal nicotine. Since health effects of PREPs are largely unknown, medicinal nicotine should be preferentially encouraged for smokers or smokeless tobacco users wishing to switch to lower‐risk products.Over the past several years, a number of new tobacco products have been introduced, some of which are being marketed, either implicitly or explicitly, as having reduced toxicant exposure or decreased health risks. To assist in evaluating these potential reduced exposure products (PREPs), the United States Food and Drug Administration in 1999 asked the Institute of Medicine to formulate methods and standards by which PREPs could be assessed.¹ More recently, an expert panel was convened to develop guidelines for the evaluation of PREPs on both individual and population levels. Among the topics addressed was human clinical testing, which included recommendations on methods and biomarkers to assess PREPs.^2,3 The recommended evaluation of PREPs included conducting studies on the pharmacokinetic properties of the products and assessing misuse liability by measuring subjective responses to the products and ability of the products to suppress withdrawal.³The use of smokeless tobacco products, in lieu of cigarettes, has been suggested as a promising method by which to reduce tobacco‐related health consequences.⁴ Currently, tobacco companies including major cigarette‐manufacturing companies are test marketing smokeless and spitless tobacco products (eg, Camel Snus by Reynolds American, Taboka by Philip Morris) as a substitute for smoking. Although overall morbidity and mortality associated with the use of moist snuff or chewing tobacco is lower than the risks associated with cigarette smoking, health consequences such as increased rates of oral and pancreatic cancers remain.^5,6 Furthermore, health effects of all forms of smokeless tobacco are not equivalent. For example, an evaluation of the content of tobacco‐specific nitrosamines found large differences between the various forms and brands of smokeless tobacco.⁷ In a human study, a significant decrease in the uptake of tobacco carcinogens has been observed when users of conventional brands of smokeless tobacco switch to Swedish snus.⁸ A comparison of several brands of moist snuff products found significant differences between brands in the amount of unionised (free) nicotine^9,10,11 and in exposure to nicotine and heart rate response after use of a single dose of each product.¹² To accurately assess the potential health effects of a product and the factors associated with consumer use, it is therefore necessary to test each smokeless tobacco product individually, including evaluating the nicotine pharmacokinetics.The purposes of this study were to assess the pharmacokinetics and subjective responses of smokeless tobacco users when using three new PREPs and to compare them with a commonly used brand of moist snuff (Copenhagen) and the medicinal nicotine lozenge (4 mg Commit). The new smokeless tobacco products studied were (1) Ariva, a compressed powdered tobacco lozenge manufactured to contain low tobacco‐specific nitrosamines by Star Scientific marketed for use by smokers when they cannot or choose not to smoke; (2) Stonewall, another compressed powdered low tobacco‐specific nitrosamine tobacco lozenge from Star Scientific marketed as a spit‐free alternative for users of traditional moist snuff smokeless tobacco products; and (3) Revel, a spit‐free smokeless tobacco packet marketed by US Smokeless Tobacco for smokers seeking a discrete alternative to smoking.     

Freshwater Ice Thickness Observations Using Passive Microwave Sensors

Walden Reservoir, a freshwater lake in north-central Colorado, was overflown six times by a NASA C-130 aircraft between January 1977 and April 1980. The aircraft was equipped with four microwave radiometers operating between 0.81 and 6.0 cm in wavelength (37.0 to 5.0 GHz). The 6.0-cm radiometer data showed a good relationship (R2 = 0.98) with ice thickness based on a sample of four ice thickness values. The 1.67- and 1.35-cm radiometer data showed weaker relationships with ice thickness. The 0.81-cm sensor data showed no positive relationship with ice thickness. None of the relationships was statistically significant because of the small sample size. The 6.0-cm sensor data in the nadir-viewing mode was found to have the most potential of all the wavelengths studied, for use in remotely determining ice thickness. The 6.0-cm radiometer probably sensed the entire thickness of the ice on the reservoir (ranging from 25.4 to 67.3 cm in thickness) and was apparently not significantly affected by the snow overlying the ice. The shorter wavelengths are scattered by the snow overlying the ice and are more suitable for snow studies than for ice thickness studies.     

Intensifying efforts to reduce child malnutrition in India: an evaluation of the Dular program in Jharkhand, India

BACKGROUND: The Dular strategy is a unique nutrition initiative initiated by UNICEF India in collaboration with the states of Bihar and Jharkhand. Designed to complement the government's Integrated Child Development Services (ICDS) and build upon its infrastructure, one of the major goals of the Dular program is to capitalize and develop community resources at the grassroots level. The emphasis of the Dular program is on establishing a community-based tracking system of the health status of women and of children 0 to 36 months of age by neighborhood-based local resource persons (LRPs). The main objectives of the Dular program include increased prenatal attendance, improvement in breastfeeding and colostrum delivery, improved nutritional practices, and decreased malnutrition. OBJECTIVES AND METHOD: An impact evaluation of 744 women and children in Jharkhand examined antenatal and birthing practices, colostrum delivery, delivery of breastmilk as first food, reported use of iodized salt, measured iodized salt status, immunization and weight-for-age z-scores (WAZ) of children 0 to 36 months of age, controlling for various measures of socioeconomic status. RESULTS: Differences were found between Dular and non-Dular villages in all major outcomes. Particularly noteworthy is that young children in Dular areas had a 45% lower prevalence of severe malnutrition and were four times more likely to receive colostrum than those in non-Dular villages. CONCLUSIONS: Our evaluation results indicate that programmatic overlays to the ICDS program, which focus primary attention on children 0 to 36 months of age and on women, have the potential to transform into a cost-effective instrument for reducing child malnutrition in India, with implications for women and children in India.     

Comparison of bactericidal activity of six lysozymes at atmospheric pressure and under high hydrostatic pressure

The antibacterial working range of six lysozymes was tested under ambient and high pressure, on a panel of five gram-positive (Enterococcus faecalis, Bacillus subtilis, Listeria innocua, Staphylococcus aureus and Micrococcus lysodeikticus) and five gram-negative bacteria (Yersinia enterocolitica, Shigella flexneri, Escherichia coli O157:H7, Pseudomonas aeruginosa and Salmonella typhimurium). The lysozymes included two that are commercially available (hen egg white lysozyme or HEWL, and mutanolysin from Streptomyces globisporus or M1L), and four that were chromatographically purified (bacteriophage lambda lysozyme or LaL, bacteriophage T4 lysozyme or T4L, goose egg white lysozyme or GEWL, and cauliflower lysozyme or CFL). T4L, LaL and GEWL were highly pure as evaluated by silver staining of SDS-PAGE gels and zymogram analysis while CFL was only partially pure. At ambient pressure each gram-positive test organism displayed a specific pattern of sensitivity to the six lysozymes, but none of the gram-negative bacteria was sensitive to any of the lysozymes. High pressure treatment (130-300 MPa, 25 degrees C, 15 min) sensitised several gram-positive and gram-negative bacteria for one or more lysozymes. M. lysodeikticus and P. aeruginosa became sensitive to all lysozymes under high pressure, S. typhimurium remained completely insensitive to all lysozymes, and the other bacteria showed sensitisation to some of the lysozymes. The possible applications of the different lysozymes as biopreservatives, and the possible reasons for the observed differences in bactericidal specificity are discussed.     

A Control Theory for Boolean Monomial Dynamical Systems

Recently criteria for determining when a certain type of nonlinear discrete dynamical system is a fixed point system have been developed. This theory can be used to determine if certain events modeled by those systems reach a steady state. In this work we formalize the idea of a “stabilizable” discrete dynamical system. We present necessary and sufficient conditions for a Boolean monomial dynamical control system to be stabilizable in terms of properties of the dependency graph associated with the system. We use the equivalence of periodicity of the dependency graph and loop numbers to develop a new O(n ²logn) algorithm for determining the loop numbers of the strongly connected components of the dependency graph, and hence a new O(n ²logn) algorithm for determining when a Boolean monomial dynamical system is a fixed point system. Finally, we show how this result can be used to determine if a Boolean monomial dynamical control system is stabilizable in time O(n ²logn).