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B Forbes

Publications and source records attributed to B Forbes.

At least 19 recordsLinked to original sources
PubMed2006

Sjögren syndrome in a child: favorable response of the arthritis to TNFalpha blockade.

Tumor necrosis factor alpha (TNFalpha) blockade has recently been found to be ineffective in treating glandular and extraglandular manifestations of adult Sjögren syndrome (SS), including arthralgia and arthritis. We report a girl who developed purpura, polyarthritis, uveitis, and severe dental caries in the first year of life and optic neuritis by age three. SS was diagnosed at 11 years of age, when severe hypokalemic renal tubular acidosis developed during infliximab treatment for arthritis. In contrast to her other disease manifestations, the arthritis responded remarkably well to TNFalpha blockade, suggesting that TNFalpha blockers may have a role in the treatment of arthritis with pediatric SS.

Acidosis, Renal Tubular↗
PubMed2006

Transesterification of p-hydroxybenzoate esters (parabens) by human intestinal (Caco-2) cells.

p-Hydroxybenzoate ester (paraben) preservatives are used in numerous orally administered products. The recognized route of metabolism for parabens is hydrolysis to p-hydroxybenzoic acid followed by conjugation and excretion. However, in the presence of alcohols, a presystemic transesterification pathway not previously reported for the human intestine can occur. Using human intestinal (Caco-2) cells, it was observed that hydrolysis of parabens to p-hydroxybenzoic acid is reduced markedly by ethanol concentrations that can occur in the human intestine, 0.25-0.5% (v/v). Ethanol concentrations of 1.0-2.5% (v/v) were optimal for transesterification to ethylparaben in Caco-2 cell homogenates. The kinetics of the transesterification reaction with regard to ethanol concentration (0-20%), time, pH (3-9), protein concentration (1-5 mg ml-1) and substrate concentration (6.25-200 microM) as well as the effects of different alcohols were studied. The Km and Vmax values for transesterification with ethanol for methyl, propyl, butyl, heptyl and octyl parabens were 449.7, 165.7, 86.1, 24.2 and 45.9 microM and 114.4, 37.5, 19.5, 7.5 and 7.6 micromol h-1 mg-1 Caco-2 cell protein, respectively. The Vmax values for transesterification of methylparaben with ethanol, propan-1-ol, butan-1-ol were 114.4, 5.1 and 4.9 micromol h-1 mg-1, respectively. Collectively, the kinetic data demonstrate that the enzyme responsible for the transesterification reaction has a preference for short-chain esters and represents the first report of transesterification in human intestinal cells. An implication of this mechanism is that alcohol-containing in vitro biosystems or protocols for the study of parabens disposition could generate transesterified artefacts. The clinical or toxicological implication is that, following co-ingestion of ester compounds with ethanol, transesterification could provide the basis for a previously unrecognized drug-alcohol interaction.

Biological Transport↗
PubMed2006

Use of simulated intestinal fluids with Caco-2 cells and rat ileum.

In most in vitro studies of oral drug permeability, little attempt is made to reproduce the gastrointestinal lumenal environment. The aim of this study was to evaluate the compatibility of simulated intestinal fluid (SIF) solutions with Caco-2 cell monolayers and Ussing chamber-mounted rat ileum under standard permeability experiment protocols. In preliminary experiments, fasted-state simulated intestinal fluid (FaSSIF) and fed-state simulated intestinal fluid (FeSSIF) solutions based on the dissolution medium formulae of Dressman and co-workers (1998) were modified for compatibility with Caco-2 cells to produce FaS-SIF and FeSSIF "transport" solutions for use with in vitro permeability models. For Caco-2 cells exposed to FaSSIF and FESSIF transport solutions, the transepithelial electrical resistance was maintained for over 4 h and mannitol permeability was equivalent to that in control (Hank's Balanced Salt Solution-treated) cell layers. Scanning electron microscopy revealed that microvilli generally maintained a normal distribution, although some shortening of microvilli and occasional small areas of denudation were observed. For rat ileum in the Ussing chambers, the potential difference (PD) collapsed to zero over 120 min when exposed to the FaSSIF transport solution and an even faster collapse of the PD was observed when the FeSSIF transport solution was used. Electron micrographs revealed erosion of the villi tips and substantial denudation of the microvilli after exposure of ileal tissue to FaSSIF and FeSSIF solutions, and permeability to mannitol was increased by almost two-fold. This study indicated that FaSSIF and FeSSIF transport solutions can be used with Caco-2 monolayers to evaluate drug permeability, but rat ileum in Ussing chambers is adversely affected by these solutions. Metoprolol permeability in Caco-2 experiments was reduced by 33% using the FaSSIF and 75% using the FeSSIF compared to permeability measured using HBSS. This illustrates that using physiological solutions can influence permeability measurements.

Animals↗
PubMed2005

Homozygous and heterozygous expression of a novel insulin-like growth factor-I mutation.

IGF-I is a key factor in intrauterine development and postnatal growth and metabolism. The secretion of IGF-I in utero is not dependent on GH, whereas in childhood and adult life, IGF-I secretion seems to be mainly controlled by GH, as revealed from studies on patients with GHRH receptor and GH receptor mutations. In a 55-yr-old male, the first child of consanguineous parents, presenting with severe intrauterine and postnatal growth retardation, microcephaly, and sensorineural deafness, we found a homozygous G to A nucleotide substitution in the IGF-I gene changing valine 44 into methione. The inactivating nature of the mutation was proven by functional analysis demonstrating a 90-fold reduced affinity of recombinantly produced for the IGF-I receptor. Additional investigations revealed osteoporosis, a partial gonadal dysfunction, and a relatively well-preserved cardiac function. Nine of the 24 relatives studied carried the mutation. They had a significantly lower birth weight, final height, and head circumference than noncarriers. In conclusion, the phenotype of our patient consists of severe intrauterine growth retardation, deafness, and mental retardation, reflecting the GH-independent secretion of IGF-I in utero. The postnatal growth pattern, similar to growth of untreated GH-deficient or GH-insensitive children, is in agreement with the hypothesis that IGF-I secretion in childhood is mainly GH dependent. Remarkably, IGF-I deficiency is relatively well tolerated during the subsequent four decades of adulthood. IGF-I haploinsufficiency results in subtle inhibition of intrauterine and postnatal growth.

Heterozygote↗
PubMed2004

Resilience and vulnerability of northern regions to social and environmental change.

The arctic tundra and boreal forest were once considered the last frontiers on earth because of their vast expanses remote from agricultural land-use change and industrial development. These regions are now, however, experiencing environmental and social changes that are as rapid as those occurring anywhere on earth. This paper summarizes the role of northern regions in the global system and provides a blueprint for assessing the factors that govern their sensitivity to social and environmental change.

Arctic Regions↗
PubMed2004

Water Environment Research Foundation (WERF) anaerobic digestion and related processes, odour and health effects study.

Biosolids odour emissions can affect the ability of wastewater utilities to implement beneficial biosolids processing and reuse programs. Communities often become more sensitised and vocal about biosolids issues, once they experience odours emanating from a nearby site. Odour impacts from biosolids, including potential human health effects, have been targeted recently by many national and local newspapers, citizens' groups, and regulatory agencies, who have raised significant concerns, ranging from viable disposal methods/sites to outright bans. Many national and local regulatory agencies in the United States are considering biosolids disposal bans in their communities because of misinformation, poor science, and citizen pressure, but primarily because of odour impact concerns. The wastewater industry has a relatively poor understanding of the operations and treatment parameters that influence biosolids odour emissions. Thus, wastewater treatment plants are often unable to control the odour quality of the biosolids that are delivered into communities. A research study to demonstrate the influence of anaerobic digestion, mechanical dewatering, and storage design and operating parameters on the odour quality of the final product was performed and is the subject of this paper. Established and new sampling and analytical methods were used to measure biosolids odour emissions from 11 test sites in North America. By determining the impacts of these control variables on biosolids odour quality, design and operations of anaerobic digestion systems might be enhanced. This paper also summarises a corollary study performed as part of the WERF research study that addresses the health effects of biosolids odours.

Community Participation↗
PubMed2002

In vivo evaluation of novel hyaluronan/chitosan microparticulate delivery systems for the nasal delivery of gentamicin in rabbits.

Biodegradable microparticles containing gentamicin were prepared using chitosan hydroglutamate (CH), hyaluronic acid (HA) and a combination of both polymers by a solvent evaporation method. These formulations were administered nasally via an insufflator. Gentamicin was also administered nasally into rabbits as a solution and powder (a physical mixture of gentamicin and lactose), intravenously (IV) and intramuscularly (IM). The resultant serum levels of gentamicin were determined by Fluorescence Polarisation Immunoassay (FPIA). The bioavailability of gentamicin was poor when administered as a nasal solution (1.1%) and dry powder (2.1%) when compared with IV. However, the microparticulate systems composed of CH and HA/CH considerably enhanced the bioavailability of gentamicin (31.4 and 42.9%, respectively,) with HA microparticles inducing a less significant enhancement (23.3%). Previous in vitro dissolution and frog palate studies indicated that these microparticulate formulations were all mucoadhesive and demonstrated prolonged drug release. Such findings were translated into an increase in the bioavailability of gentamicin when compared with a simple nasal solution in vivo. When HA and CH were combined in the HA/CH formulation, the polymers appeared to improve the absorption of incorporated gentamicin synergistically in comparison to the individual polymers, suggesting a promising nasal delivery system.

Adjuvants, Pharmaceutic↗
PubMed2002

Adaptive resistance to benzalkonium chloride, amikacin and tobramycin: the effect on susceptibility to other antimicrobials.

AIMS: To produce strains of antimicrobial-resistant Pseudomonas aeruginosa via adaptation to benzalkonium chloride, amikacin and tobramycin and to then examine the incidence, or otherwise, of cross-resistance between antibiotics and between antibiotics and benzalkonium chloride. METHODS AND RESULTS: Adaptation was obtained by progressive subculturing in subinhibitory concentrations of the antimicrobials. Pseudomonas aeruginosa NCIMB 10421 adapted to grow in high concentrations of benzalkonium chloride (BC) had lower MIC to antibiotics than the wild type, whereas Ps. aeruginosa adapted to grow in antibiotics had greater MIC to benzalkonium by a small degree. CONCLUSIONS: Adaptive resistance to BC of Ps. aeruginosa generally produced cultures with a decrease in resistance to several antibiotics. Adaptive resistance to the aminoglycosides Ak and Tm produced a low-level increase in tolerance to BC. The adaptive mechanisms of resistance appear to be different for the different types of antimicrobials used. SIGNIFICANCE AND IMPACT OF THE STUDY: The relationships between biocide and antibiotic resistance are complex. It appears, from this study, that an organism resistant to a common biocide can become sensitive to antibiotics, but the converse was not true. Could this observation be used in a strategy to alleviate antibiotic resistance?

Adaptation, Physiological↗
PubMed2001

In vivo and in vitro characterization of novel microparticulates based on hyaluronan and chitosan hydroglutamate.

This study examined the application of previously characterized microparticles composed of hyaluronan (HA) and chitosan hydroglutamate (CH) as well as novel microparticles consisting of both polymers (HA/CH) to improve the nasal delivery of a model drug. The rabbit bioavailabilities of gentamicin incorporated in HA, CH, and HA/CH microparticles were increased 23-, 31-, and 42-fold, respectively, compared with the control intranasal solution of gentamicin, indicating that all test microparticles were retained for longer periods on the nasal mucosa of the rabbits as supported by previous in vitro dissolution as well as frog palate mucoadhesion studies, thereby improving drug absorption. The higher bioavailabilities of CH-based formulations (CH and HA/CH) suggest the penetration-enhancing effects of CH may also be partially responsible for the improvement. A model was developed, based on a glass impinger device, to deliver dry powder formulations reproducibly onto the surface of cultured cell monolayers. In vitro permeability and fluorescence microscopy studies on the tight junctions of the 16HBE14o- cell lines further confirmed the ability of CH-based formulations to enhance penetration. Furthermore, the in vitro absorption profile from cell culture studies was consistent with those determined from in vivo studies. The complementary effect from the mucoadhesive nature of HA coupled with the penetration-enhancing effects of CH makes the novel HA/CH formulation a promising nasal delivery system.

Administration, Intranasal↗
PubMed2001

Activation of clindamycin phosphate by human skin.

AIMS: To investigate the relative antimicrobial activity of clindamycin phosphate (CP) and clindamycin (Cly) and to examine the effect of skin homogenates on the activity of CP. METHODS AND RESULTS: Minimum inhibitory concentrations (MIC) were determined against dermally relevant organisms and bactericidal activity was studied using time-kill methodology. The effect of skin homogenates on the antimicrobial activity of CP was studied by well-diffusion assay. The MIC of Cly was substantially lower than that of CP in all susceptible organisms. Clindamycin also showed greater bactericidal activity (rate of kill) than CP. Phosphatases in skin homogenates activated CP at pH 4-8 with a maximal activation at pH 4. CONCLUSION: Phosphatases within the skin have been shown to convert CP to the more potent form Cly. SIGNIFICANCE AND IMPACT OF THE STUDY: Conversion to Cly is a major determinant of antimicrobial activity in the skin layers following topical application of CP.

Anti-Bacterial Agents↗
PubMed2001

The relationships and susceptibilities of some industrial, laboratory and clinical isolates of Pseudomonas aeruginosa to some antibiotics and biocides.

AIMS: To provide evidence to support or refute the hypothesis that cross-resistance between antibiotics and biocides can occur. METHODS AND RESULTS: Fifty-five strains of Pseudomonas aeruginosa were tested for their resistance to anti-pseudomonal antibacterials. Twenty clinical, 19 industrial and 16 culture collection isolates were used. The MIC was found for the antibiotics amikacin, ceftazidime, ciprofloxacin, gentamycin, ticarcillin, tobramycin, imipenem and polymyxin B. The MIC was also found for the biocides benzalkonium chloride and chlorhexidine. The analysis of the data was based on the production of a normal distribution of the log (MIC) plots for each antimicrobial. Strains were then labelled as resistant, intermediate or sensitive based on the mean and standard deviation of the distributions. CONCLUSIONS: In general the clinical isolates were the most recalcitrant organisms, with the industrial isolates being the most sensitive. SIGNIFICANCE AND IMPACT OF THE STUDY: The work shows that antibiotic/biocide correlations do occur, especially with clinical strains. That such correlations were not found with industrial isolates suggests that the clinical environment is responsible for the correlation. We could infer that it is the selective pressure of antibiotic usage that differentiates the clinical environment from the industrial.

Animals↗
PubMed2001

Bear mauling: a descriptive review.

OBJECTIVE: Provide a descriptive review of bear and human interactions in the United States. STUDY DESIGN: Descriptive review. RESULTS: The bear population in the United States includes the grizzly bear, the polar bear, and the black bear, including the glacier phase or blue bear. As the human population grew and remote or wilderness access improved, the bear population suffered both in total numbers and safe habitat. Conservation efforts, such as hunting restrictions and habitat enhancement, have helped to increase the total numbers of bears on the North American continent. The chance of a human encountering a bear increases as the remote bear territory diminishes. Bear incidents are widely publicized, though few serious incidents occur. The authors have direct knowledge of these bear-human encounters in Alaska. Serious human injuries from black bears, or maulings, including fatalities are uncommon. Grizzly bears when trapped or stimulated may be very dangerous. The polar bear sees everything that moves or has color, as potential food, and therefore, will attack seemingly unprovoked. CONCLUSIONS: The chance of a human encountering a bear increases as the remote bear territory diminishes. Bear incidents are widely publicized, though few serious incidents occur.

Animals↗
PubMed2000

Formulation of inhaled medicines: effect of delivery vehicle on immortalized epithelial cells.

The small volume of airway lining fluid renders it susceptible to alteration by the deposition of inhaled formulations. The increasing popularity of the pulmonary route for drug delivery has led to an increasing number of pharmaceutical excipients being incorporated into inhaled dosage forms. The effects of drug delivery vehicle on airway epithelial cells can be studied with the aid of cell culture models of the respiratory epithelium. The effects of pH, osmolarity, and lactose on epithelial cell layers were studied using 16HBE14o- cells. Mannitol flux was used to assess epithelial permeability, enzymatic conversion of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) was used as a measure of epithelial cell metabolism, and release of the cytosolic enzyme lactate dehydrogenase was used as a measure of cell integrity. The effect of buffer composition on epithelial cell mucus secretion was studied using HT29-clone H cells, with mucus secretion measured using an enzyme-linked lectin assay. The permeability of 16HBE14o- cell layers was increased by apical fluid of pH 5, 6, and 9 as well as osmolarities of 96 and 545 mOsm. MTT conversion was reduced by apical fluid of pH 5 and 6 and osmolarity of 96 mOsm. Lactate dehydrogenase release was only increased by apical fluid of pH 9. No effect of lactose solution (100 mM) on the epithelial cells was observed. Mucus secretion by HT29-clone H cells was lowest in Dulbecco's modified Eagle medium (2.92 +/- 0.23 ng per cell layer) and was increased in phosphate-buffered saline with magnesium and calcium (4.28 +/- 0.38 ng per cell layer) and phosphate-buffered saline without magnesium and calcium (6.56 +/- 0.72 ng per cell layer). These results suggest that the physicochemical properties of inhaled formulations should be carefully controlled. The effect of buffer composition on mucus secretion suggests that even the application of "physiological" solutions may affect the epithelium. These cell models represent an opportunity to investigate the interaction of drug delivery vehicles with the epithelium.

Analysis of Variance↗
PubMed2000

Mitigation of surfactant erythrocyte toxicity by egg phosphatidylcholine.

Polyoxyethylene alkyl ether surfactants have been shown to have excellent penetration enhancing abilities although they are associated with a high level of local toxicity. We have compared the toxicity of a range of polyoxyethylene alkyl ethers (Brij 96, Brij 76, Brij 56, 10 lauryl ether and 9 lauryl ether) to an anionic surfactant (sodium dodecyl sulphate (SDS)), an ampholytic surfactant (lysophosphatidylcholine) and a cationic surfactant (tetradecyltrimethylammonium bromide (TTAB)), in the presence and absence of egg phosphatidylcholine. The toxicity of the surfactants or phospholipid/surfactant mixtures was assessed by measuring haemolytic activity. The test samples were incubated with a suspension of red blood cells for 30 min and Drabkin's reagent was used to indicate the amount of haemoglobin released. All of the polyoxyethylene alkyl ethers, SDS, TTAB and lysophosphatidylcholine exhibited haemolytic activity at concentrations between 0.10 and 0.25 mM. The addition of egg phosphatidylcholine reduced the toxicity for all of the surfactants, with the toxicity of Brij 96 being mitigated to a greater extent than the toxicity of the other polyoxyethylene surfactants examined. The rate of haemolysis induced by Brij 96 or 10 lauryl ether was also reduced by increasing concentrations of phosphatidylcholine. As the phosphatidylcholine content of a mixed surfactant system comprising egg phosphatidylcholine: Brij 96 was replaced by lysophosphatidylcholine and fatty acid, the haemolytic action of the mixture increased markedly. The results from this study show that the toxicity of surfactants to erythrocytes can be mitigated by the addition of egg phosphatidylcholine. Synthetic surfactants combined with phosphatidylcholine may generate drug delivery systems worthy of more extensive investigation.

Drug Delivery Systems↗
PubMed1999

Temporal dependence of ectopeptidase expression in alveolar epithelial cell culture: implications for study of peptide absorption.

There is little data available regarding the extent of peptide metabolism encountered following inhalation to the lung. We have studied the activity of five ectopeptidases in primary rat alveolar epithelial cells, A549 cells and pulmonary macrophages. Peptidase activity was assayed in the plasma membrane fractions (PMF) of primary type II alveolar epithelial cells (ATII cells) after 2 days in culture and after 7 days in culture when they had formed monolayers of type I-like cells (ATI-like cells). Dipeptidyl peptidase IV (DPP) activity fell from 36.65 mU/mg protein to 16.29 mU/mg protein between day 2 and day 7 in culture, aminopeptidase N (AMN) activity increased from 16.16 mU/mg protein to 23.99 mU/mg protein, angiotensin-converting enzyme (ACE) activity was lost (4.29 mU/mg protein at day 2, not detected at day 7), and carboxypeptidase M (CPM) activity was acquired (not detected at day 2, 5.20 mU/mg protein at day 7). The profile of exopeptidase expression in A549 cells was similar to that of primary rat alveolar cells at day 7 in culture (DPP 24.24 mU/mg protein, AMN 47.74 mU/mg protein, CPM 4.28 mU/mg protein, ACE not detected). Macrophages expressed high levels of aminopeptidases (DPP 46.85 mU/mg protein, AMN 28.28 mU/mg protein) but carboxypeptidase activity was not detected. Low neutral endopeptidase 24.11 (NEP) activity was found in all cell types studied (0.96-2.41 mU/mg protein). The qualitative and quantitative changes in the peptidase activity of primary cultured rat alveolar cells between day 2 and day 7 in culture has implications for the use of alveolar cell monolayers as drug absorption models to investigate peptide absorption from the lung. Ectopeptidase activity in cultured alveolar cells can be used to infer the peptide-metabolising capacity of the surface of the alveolar epithelium. The aminopeptidase activity in particular, if representative of enzyme activity in vivo, would offer a significant metabolic barrier to systemic delivery of peptides via the lung.

Absorption↗
PubMed1997

Smoking cessation in military personnel.

Tobacco use is the single most important preventable cause of death in military personnel. The purpose of this randomized clinical trial was to evaluate the effectiveness of two behavioral interventions when added to nicotine-replacement therapy on smoking cessation. The sample of 512 included 52% active duty military, 29% family, 11% retirees, and 8% Department of Defense civilians. There was a main effect of compliance at the end of the program (EOP); 69% of those who attended 75% of the classes were abstinent from tobacco; regression analysis found the more intensive program to be twice as effective at EOP and at 3 months, an outcome not continued at 6 months. The longer, more intensive Vanderbilt University Medical Center program was significantly more effective at helping the civilian portion of the population (85% versus 60% in the American Cancer Society program) but not the active duty participants.

Adult↗