Control of Established Gingivitis and Dental Plaque Using a 1450 ppm Fluoride/Zinc-based Dentifrice: A Randomized Clinical Study.

PURPOSE: To investigate the clinical efficacy in controlling established gingivitis and dental plaque of a 1450 ppm fluoride as sodium monofluorophosphate (SMFP)/zinc-based dentifrice, as compared to a zinc-free dentifrice with 1450 ppm fluoride as SMFP after six months product use. METHODS: A six-month clinical study, with eighty-six (86) subjects, was conducted in Chengdu, China, using a double-blind, randomized, parallel-group treatment design. After a baseline evaluation, study subjects were randomly assigned to one of the two study treatments: 1) 1450 ppm fluoride as SMFP/zinc-based dentifrice (Test) or 2) 1450 ppm fluoride as SMFP/zinc-free dentifrice (Negative Control). Subjects were provided with a soft bristle toothbrush and brushed their teeth twice daily (morning and evening) for one minute with their assigned dentifrice. After three months, and again after six months of product use, subjects returned to the testing facility for their followup gingivitis and plaque examinations. Statistical analyses were performed separately for the gingivitis assessments and dental plaque assessments using the appropriate statistical methods. All statistical tests of hypotheses were two-sided, and employed a level of significance of α = 0.05. RESULTS: After three and six months of product use, subjects assigned to the Test treatment exhibited statistically significant (p < 0.001) reductions in gingival index and plaque index scores as compared to subjects assigned to the Negative Control treatment. CONCLUSION: The results of this single-center, double-blind, parallel-group and randomized clinical study support the conclusion that a 1450 ppm fluoride as SMFP/zinc-based dentifrice provides clinically meaningful and statistically significant reductions in gingivitis (23.8%) and dental plaque (22.5%) as compared to a 1450 ppm fluoride as SMFP/zinc-free dentifrice over a six-month period of twice-daily product use.

A comparative study of the effects on the skin of a classical bar soap and a syndet cleansing bar in normal use conditions and in the soap chamber test.

BACKGROUND/AIMS: The skin irritation potential of a body cleansing product is often compared under exaggerated test conditions, although the product is intended to be used at home with repetitive and brief contact with the skin. The aim of this study was to determine how much patch testing is predictive of the clinical, sub-clinical and subjective cutaneous effects of products used at home by consumers for their normal hygienic cleansing. METHODS: A double-blind comparative study of the normal use of an alkaline soap bar and a syndet at home during 10 consecutive weeks was performed on two identical groups of 25 healthy female subjects. The eventual skin changes observed at different anatomical skin sites were evaluated by clinical visual examination and by bioengineering measurements before the start of the study and then every 2 weeks. The objective measurements were compared with the subject's perceptions of dryness, tightness and product irritancy during the testing. RESULTS: The bioengineering measurements did not show any significant changes on all the anatomical skin sites, except for a small increase in skin pH with the classical soap bar. However, a trend appeared, showing that the alkaline soap bar is perceived by the subjects themselves as more of an irritant than the syndet bar. In the soap chamber test, the bar soap showed a significantly higher irritancy than the syndet bar. CONCLUSION: This study showed that cutaneous irritation induced by cleansing products in patch testing is not necessarily predictive of the irritation likely to occur in normal use conditions. Finally, a clear relationship could be demonstrated between the results of the soap chamber test and the consumer perception of both cleansing bars.

Subclinical, non-erythematous irritation with an open assay model (washing): sodium lauryl sulfate (SLS) versus sodium laureth sulfate (SLES).

Compared to exaggerated hand washing procedures, an open non-exaggerated assay better approximates consumer surfactant use. Our goal was to observe skin surface modifications induced by an open test with regard to discriminating between surfactant solutions. This human in vivo assay provided information about the effect of only three washes at the laboratory and a week of at-home use. Dorsal hand and volar forearm were compared. The results demonstrated that this clinical model permits exploration of subclinical surfactant-induced irritation. Both the volar forearm and the dorsal hand are capable of discriminating between the effects of sodium lauryl sulfate (SLS) and sodium laureth sulfate (SLES). Squamometry proved to be a sensitive assessment technique for detecting surfactant-induced subclinical skin surface alterations and for differentiating surfactant effects in this open application assay, in as few as three washes.

Early and selective pathology of light chain neurofilament in the spinal cord and sciatic nerve of G86R mutant superoxide dismutase transgenic mice.

Pathologic accumulation of neurofilament protein (NF), both within spheroids of the proximal axon and within inclusions of motor neuron somata, is a hallmark of neurodegeneration in amyotrophic lateral sclerosis (ALS). Transgenic mice that express mutations in superoxide dismutase (SOD-1), which were genetically linked to familial ALS, develop symptomatology and pathology that strongly resemble ALS and therefore provide a useful model for studying the disease. Examining NF in the G86R mutant SOD-1 transgenic mice, we previously demonstrated that phosphorylated NF accumulates in motor neuron somata of symptomatic transgenic mice. In the present study, we expand these results by examining the immunocytochemical distribution of the three subunits of NF (i.e., light, medium, and heavy chains) as well as tubulin in presymptomatic and symptomatic SOD-1 transgenic mice. Although all NF subunits, but not tubulin, accumulate along with phosphorylated NF in the spinal cord inclusions of symptomatic mice, numerous inclusions containing only light chain NF are found in the spinal cord of presymptomatic SOD-1 transgenic mice. In addition to these results in the spinal cord, intensely immunoreactive aggregates of NF-L, but not the other NF subunits or tubulin, were observed in the sciatic nerve of both symptomatic and presymptomatic mutant SOD-1 transgenic mice. These results suggest that the mechanism of NF alteration in SOD-1 transgenic mice, and also perhaps in ALS patients, originates with the disruption of NF-L, only later involving the other subunits.

An open assay model to induce subclincal non-erythematous irritation.

To avoid the acute irritation and dryness that a single occlusive surfactant application (24-h patch test) may cause, and to approximate clinical use, an open application model was chosen to define subclinical non-erythematous irritation in the stratum corneum. This human test combined a supervised washing at the laboratory with at-home use of the test products by the subjects. Effects of washing with the surfactants on the dorsal hand and volar forearm were compared. The results demonstrated that this situational use model permits the exploration of subclinical surfactant-induced irritation. The forearm appeared to be more discriminative as compared to the dorsal hand. Squamometry proved to be a sensitive, complementary assessment method for detecting surfactant-induced subclinical skin surface alterations and for differentiating surfactant effects in this open assay.

Amyotrophic lateral sclerosis associated with mutations in superoxide dismutase: a putative mechanism of degeneration.

Amyotrophic lateral sclerosis (ALS) is a devastating neurologic disease that rapidly progresses from mild motor symptoms to severe motor paralysis and premature death. Until recently, there were few substantive studies conducted on the pathogenesis of the disease. With the genetic linkage of mutations in the superoxide dismutase (SOD-1) gene with familial ALS patients, new avenues for study have become available including transgenic mice and culture models. Although not yet providing a complete picture of the disease mechanism, studies utilizing these model systems have greatly advanced our understanding of the mechanism of degeneration and should eventually lead to putative therapeutic agents. In this review, we will present the important findings from these model systems, provide a framework in which to evaluate these findings, and speculate on the mechanism of degeneration initiated by the mutations in SOD-1.

The effects of prolonged use of surfactants on the skin of normal and photo-exposed hairless mice.

Laboratory tests to assess the irritant potential of materials, such as skin cleansers, which are normally used over a long period by humans, fail to mimic actual use. Most washing tests last a few days or at most a few weeks. Skin sites and techniques are often not standardized. The more standardized patch test involves occlusion and results in exaggerated reactions, since even water and blank patches produce visible and pathophysiologic changes. All of these tests rely on visual assessment despite strong evidence that similarly appearing skin can be very different histologically. The primary objective of this study was to use a well-defined animal model to evaluate the cumulative effects of repeated skin exposure to low levels of surfactants of varying skin irritation potential. A secondary aim was to examine whether or not surfactant-induced skin changes were exacerbated by suberythemal UV radiation. Test materials were applied topically, 2x daily to the dorsal areas of normal and low-dose solar simulator exposed mice for 15 weeks. Our results show that, with conditions mimicking typical normal use, these surfactants and skin cleansers produce little or very mild histological changes in the skin. UV irradiation alone produced the greatest change in all histological parameters examined, with no synergistic or additive effects with the topical treatments.

Determinants of neuronal vulnerability in neurodegenerative diseases.

Selective neuronal vulnerability can be defined anatomically by the differential vulnerability of circuits and neurochemically by the vulnerability of neurons that differentially express particular proteins. The anatomic perspective is exemplified by the vulnerability of the nigrostriatal projection in Parkinson's disease (PD), the degeneration of upper and lower motor neurons in amyotrophic lateral sclerosis (ALS), and the preferential loss of long corticocortical projections in Alzheimer's disease (AD). The neurochemical perspective is reflected in the heightened vulnerability of neurons that normally express high somatodendritic levels of neurofilament (eg, entorhinal and association cortices in AD, the spinal cord in a mouse model of ALS, and the retina in a primate model of glaucoma), as well as the reduced vulnerability of neurons that express calcium-binding proteins (eg, neocortex of AD patients, the spinal cord and brainstem of ALS patients, and the spinal cord of a mouse model of ALS). By combining neurochemical and anatomic correlates of vulnerability, an integrated view of vulnerable neurons is emerging in which characteristics of vulnerable neurons appear to transcend both brain region and disease state, suggesting that neurodegenerative disorders share common mechanisms of degeneration.

Superoxide dismutase and neurofilament transgenic models of amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a devastating neurologic disease characterized by progressive motor dysfunction that leads to paralysis and eventually death. There are numerous hypotheses for the pathogenesis of this disease, but the mechanisms of degeneration were difficult to investigate before the development of animal models. Transgenic mice with alterations in either the superoxide dismutase (SOD-1) or neurofilament genes display motor neuron pathology and deficits in motor function and, therefore, provide animal models for the study of ALS neurodegeneration. Using these animal models, as well as several in vitro models, researchers have made rapid progress during the last several years toward understanding the cause and mechanism of ALS neurodegeneration. These studies have demonstrated that motor neuron degeneration in ALS may be secondary to a number of causes, including neurofilament disruption, mutations in SOD-1, and glutamate excitotoxicity. Although each of these mechanisms can cause motor neuron degeneration by itself, studies of transgenic mice have indicated several points at which these mechanisms may interact, suggesting that they are components of one general mechanism of neurodegeneration.

Light and electron microscopic distribution of the AMPA receptor subunit, GluR2, in the spinal cord of control and G86R mutant superoxide dismutase transgenic mice.

Excitotoxicity has been hypothesized to contribute to amyotrophic lateral sclerosis (ALS) neurodegeneration. The similar pattern of vulnerability in the spinal cord of mutant superoxide dismutase (SOD-1) transgenic mice and mice treated with excitotoxins supports a role for excitotoxicity in the mechanism of degeneration. The distribution of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) class of glutamate receptors (GluRs) with different calcium permeabilities has been proposed as an explanation for this differential vulnerability. GluR2 appears to be the dominant determinant of calcium permeability for AMPA receptors; thus, it is critical for their contribution to excitotoxic mechanisms. In this study, we investigate the distribution of GluR2 immunoreactivity in the spinal cord of control and SOD-1 transgenic mice. GluR2 immunoreactivity is present equally within vulnerable neurons (i.e., motor neurons and calretinin-immunoreactive neurons) as well as nonvulnerable neurons (i.e., calbindin-immunoreactive neurons and dorsal horn neurons). In addition, postembedding immunoelectron microscopy reveals that GluR2 is present in synapses of dorsal and ventral horn neurons and that the percentage of labeled synapses and numbers of immunogold particles per synapse do not vary between these spinal cord regions. Comparing control mice with SOD-1 transgenic mice, at both the light and the electron microscopic levels, the distribution and intensity of GluR2-immunoreactivity do not appear to be altered. These results suggest that the cellular and synaptic distribution of GluR2 is not a determinant of the selective vulnerability observed in SOD-1 transgenic mice or in ALS patients.

Time course of neuropathology in the spinal cord of G86R superoxide dismutase transgenic mice.

Transgenic mice with a G86R mutation in the mouse superoxide dismutase (SOD-1) gene, which corresponds to a mutation observed in familial amyotrophic lateral sclerosis (ALS), display progressive motor dysfunction leading to paralysis and premature death. In endstage SOD-1 transgenic mice, there is marked loss of spinal motor neurons and interneurons, accumulation of phosphorylated neurofilament inclusions, and reactive astrocytosis. The present study details the time course and ultrastructural appearance of these pathologic changes and correlates the timing of these events with the behavioral symptoms. There is no significant reduction in the number of total neurons, motor neurons, or interneurons in the ventral spinal cord of presymptomatic mice, as compared to age-matched control mice. In contrast, there is a significant reduction in the number of total neurons (-23.5%), motor neurons (-28.9%), and interneurons (-23.5%) in symptomatic SOD-1 transgenic mice. This neuron loss correlates temporally with the onset of reactive astrocytosis and the appearance of phosphorylated neurofilament inclusions. The identical timing of motor neuron and interneuron degeneration in this model of ALS strongly suggests that degeneration in the spinal cord of patients with ALS is not specifically directed at motor neurons, but rather more generally at several populations of neurons in the spinal cord. In addition, the late onset and rapid progression of neuron loss suggest that a toxic property is accumulating while the SOD-1 transgenic mice are presymptomatic, and that this toxic property must reach a threshold level before the onset of neuronal degeneration.

Open application assay in investigation of subclinical irritant dermatitis induced by sodium lauryl sulfate (SLS) in man: advantage of squamometry.

BACKGROUND/AIMS: After a single occlusive application (24 h patch test), SLS can cause irritation, dryness, and tightness. In typical use, clinical surfactant exposure is usually brief, of open application, and cumulative. The open application model becomes relevant when phenomena, such as dryness and subclinical, i.e., non-visible, irritation are induced. METHODS: Exaggerated hand wash was performed in a total of 21 healthy individuals. Signs of skin irritation were scored, and skin reactions were measured using various bioengineering techniques. RESULTS: These studies demonstrate that an exaggerated hand wash model permits exploration of sub-clinical irritation. CONCLUSIONS: Squamometry proved to be a sensitive, complementary method to detect surfactant-induced, sub-clinical skin alterations.

Quantitative immunocytochemical analysis of the spinal cord in G86R superoxide dismutase transgenic mice: neurochemical correlates of selective vulnerability.

Transgenic mice with a G86R mutation in the mouse superoxide dismutase (SOD-1) gene, which corresponds to a mutation that has been observed in familial amyotrophic lateral sclerosis (ALS), display progressive loss of motor function and provide a valuable model of ALS. The pathology in the spinal cords of these mice was evaluated to determine whether there are chemically identified populations of neurons that are either highly vulnerable or resistant to degeneration. Qualitatively, there were phosphorylated neurofilament protein (NFP)-immunoreactive inclusions and a pronounced loss of motoneurons in the ventral horn of the spinal cord without the presence of vacuoles that has been reported in other SOD-1 transgenic mice. Neuron counts from SOD-1 and control spinal cords revealed that the percentage loss of NFP-, choline acetyltransferase (ChAT)-, and calretinin (CR)-immunoreactive neurons was greater than the percentage loss of total neurons, suggesting that these neuronal groups are particularly vulnerable in SOD-1 transgenic mice. In contrast, calbindin-containing neurons did not degenerate significantly and represent a protected population of neurons. Quantitative double-labeling experiments suggested that the vulnerability of ChAT- and CR-immunoreactive neurons was due primarily to the presence of NFP within a subset of these neurons, which degenerated preferentially to ChAT- and CR-immunoreactive neurons that did not colocalize with NFP. Our findings suggest that NFP, which has been demonstrated previously to be involved mechanistically in motoneuron degeneration, may also be important in the mechanism of degeneration that is initiated by the SOD-1 mutation.

Self-perceived sensory responses to soap and synthetic detergent bars correlate with clinical signs of irritation.

BACKGROUND: Epidemiologic studies indicate that after using soaps and other personal care products, many consumers experience irritation. In 50% of the cases the feelings of skin dryness, itching, and stinging occur in the absence of visible signs of irritation. OBJECTIVE: We sought to determine the relation between self-perceived sensory responses of panelists to cleansing products and clinical signs of irritation. METHODS: A combination of exaggerated arm-washing methods was designed to induce clinical signs of irritation with psychometric techniques developed to quantify sensations. RESULTS: Two studies demonstrated that panelists could reproducibly differentiate between products on the basis of the sensations they felt and that there was a significant correlation (frequently r > 0.80) between these and the observable signs. In the case of skin dryness panelists differentiated products several washing cycles before observable differences were detected. CONCLUSION: Sensory evaluations of irritation yield additional information on soap and detergent irritancy beyond clinical observations and expand understanding of the irritation process.

Skin irritancy classification of body cleansing products: Comparison of two test methodologies.

BACKGROUND/AIMS: Mildness of skin cleansing products is often claimed although difficult to substantiate. Both the society and the producer share a common interest that cleansing products are safe in use and that valid methods are used for premarketing evaluation of new products. The object of the present study was to evaluate methodological aspects when three products were compared using two different test systems to characterize their irritant properties. METHODS: A modified soap chamber test (M-SCT) and an iterative short-term patch test (IPT) were performed. Eight healthy female volunteers aged 18 to 55 selected as having responsive skin were studied. Colorimetry and measurement of transepider-mal water loss was employed. A soap, a synthetic detergent bar and a facial cleanser were studied with deionized water as a reference. RESULTS: The IPT appeared more sensitive than the M-SCT for the detection and discrimination of irritation. The techniques allowed the ranking of the irritant properties of the products relative to water, which showed low values in both systems. CONCLUSION: Ranking of irritant properties of cleansing products was possible even in a limited number of individuals. Iterative short-term patch test was more sensitive than a modified soap chamber test.

Corneometiy measurements to evaluate skin dryness in the modified soap chamber test.

BACKGROUND/AIMS: Patch test procedures have been developed to compare the irritation potential of surfactant-based products. Skin changes due to product application are usually assessed visually by a trained evaluator using standard scoring scales or instrumentally. This study has been carried out to optimize the assessment of skin dryness in the Modified Soap Chamber Test both by visual scoring and Comeometer measurement, with transepidermal water loss as an additional measure. METHODS: Products were applied, under occlusion, to the skin, for 2 successive periods of 24 and 21 h; skin reactions were evaluated 3 h after removal of each series of patches, and followed up to 7 days after patches had been removed. RESULTS: Skin dryness progressively develops after patch removal, and reaches a maximum 3 to 5 days later. Capacitance measurements correlate the best with visual scoring of dryness when waiting 5 days after patch removal before assessment. CONCLUSIONS: Comeometer is an useful instrument to quantify observed dryness only when transepidermal water loss has recovered a value close to its baseline value. For both visual and instrumental assessments of skin dryness, waiting 3 to 5 days after patch removal in the Modified Soap Chamber Test will provide the most valuable results.

Infant mortality in Sri Lankan households: a causal model.

The infant mortality rate in Sri Lanka has fallen precipitiously since World War II, to 44 per 1000 births, a rate that is similar to a number of Western Countries. Yet the aggregated country rate masks wide variations across districts, from a low 21 per 1000 in Jaffna District to a high of 100 per 1000 in Nuwara Eliya District. Such regional variations in infant mortality rates have been shown to be related to a number of social, demographic and intitutional characteristics of each area. To specify such linkages we move, in this paper, from the aggregate level of analysis to the level of individual households in order to look for social, economic and other characteristics associated with infant deaths. Data are derived from a systematic interview of 480 household heads in 12 villages of Sri Lanka, collected in 1980. The most proximate factors, public health or medical variables, that predict infant death in particular households include quality of family nutrition, supervised childbirth, immunization of children and, most significant, whether the family has a sanitary latrine. Yet these medical variables are strongly associated with educational and economic characteristics of the family which, in turn, are predictive of infant mortality. Poor families and poorly educated mothers are less likely to go to hospital for childbirth, have a latrine, etc., and more likely to have had an infant die. Underlying the variations in education and economic status are variations in ethnic group; families with poor sanitation, least education and few economic resources are most likely to be members of the minority communities, Ceylon or Indian Tamils and Muslims. Minority group membership is significantly associated with infant mortality as well. When a set of medical, educational, economic and cultural variables are examined simultaneously within a path model we show that the best causal explanation of infant death in Sri Lankan households says, "Minority group status results in poverty which prevents families from having safe sanitary facilities which causes infant death". Infant mortality in Sri Lanka is thus not simply a medical problem to be dealt with by public health programs, nor is it solely an economic problem that can be solved with creation of jobs, but it is better seen as a problem of the structure of the whole society.