Uso de hidroxiapatita de cálcio no tratamento da dermatoporose / Use of calcium hydroxyapatite in the treatment of dermatoporosis

A dermatoporose é a síndrome de fragilidade cutânea. Acomete principalmente indivíduos acima de 60 anos, com maior prevalência no sexo feminino. Os principais fatores de risco são: envelhecimento, exposição solar intensa e uso de corticoterapia tópica e sistêmica. Se manifesta clinicamente por atrofia cutânea, púrpuras senis, pseudo cicatrizes estrelares e lacerações, podendo evoluir com hematomas dissecantes e infecções graves. Trata-se de uma doença com grande impacto na qualidade de vida dos pacientes e, até o presente momento, não há terapias com resultados satisfatórios. Hidratação, vitamina C tópica e oral, luz intensa pulsada foram algumas das terapêuticas estudadas. A hidroxiapatita de cálcio é um bioestimulador de colágeno composto por microesferas em um veículo de carboximetilcelulose (Radiesse®). Tem sido usada para estimular a produção endógena de colágeno e consequentemente melhorar a qualidade e espessura da pele. Este efeito do produto poderia melhorar o quadro clínico da dermatoporose. O estudo teve como objetivo avaliar a melhora das lesões purpúricas e da atrofia da pele após aplicação de Radiesse® no antebraço de 5 pacientes portadores de dermatoporose no setor de Dermatologia do Hospital do Servidor Público Municipal de São Paulo. Os 5 pacientes foram submetidos a aplicação de Radiesse® nos antebraços e foram avaliadas 45 e 90 dias após o procedimento, o número de lesões purpúricas, grau de atrofia da pele através do teste de pinçamento e realizado comparação fotográfica. Após o tratamento, observou-se melhora do número das lesões purpúricas, melhora da atrofia da pele e melhora da qualidade de pele quando comparada fotograficamente. Dessa forma, o tratamento com Radiesse® mostrou-se promissor, com resultados satisfatórios e com um bom perfil de segurança. Palavras-chave: Dermatoporose. Púrpura senil. Radiesse. Bioestimulador. Tratamento.

Carmellose Mucoadhesive Oral Films Containing Vermiculite/Chlorhexidine Nanocomposites as Innovative Biomaterials for Treatment of Oral Infections.

Infectious stomatitis represents the most common oral cavity ailments. Current therapy is insufficiently effective because of the short residence time of topical liquid or semisolid medical formulations. An innovative application form based on bioadhesive polymers featuring prolonged residence time on the oral mucosa may be a solution to this challenge. This formulation consists of a mucoadhesive oral film with incorporated nanocomposite biomaterial that is able to release the drug directly at the target area. This study describes the unique approach of preparing mucoadhesive oral films from carmellose with incorporating a nanotechnologically modified clay mineral intercalated with chlorhexidine. The multivariate data analysis was employed to evaluate the influence of the formulation and process variables on the properties of the medical preparation. This evaluation was complemented by testing the antimicrobial and antimycotic activity of prepared films with the aim of finding the most suitable composition for clinical application. Generally, the best results were obtained with sample containing 20 mg of chlorhexidine diacetate carried by vermiculite, with carmellose in the form of nonwoven textile in its structure. In addition to its promising physicomechanical, chemical, and mucoadhesive properties, the formulation inhibited the growth of Staphylococcus and Candida; the effect was prolonged for tens of hours.

Spray drying formulation of albendazole microspheres by experimental design. In vitro-in vivo studies.

Both an experimental design and optimization techniques were carried out for the development of chitosan-pectin-carboxymethylcellulose microspheres to improve the oral absorption of albendazole as a model drug. The effect of three different factors (chitosan, pectin and carboxy methyl cellulose concentrations) was studied on five responses: yield, morphology, dissolution rate at 30 and 60 min, and encapsulation efficiency of the microspheres. During the screening phase, the factors were evaluated in order to identify those which exert a significant effect. Simultaneous multiple response optimizations were then used to find out experimental conditions where the system shows the most adequate results. The optimal conditions were found to be: chitosan concentration, 1.00% w/v, pectin concentration 0.10% w/v and carboxymethylcellulose concentration 0.20% w/v. The bioavailability of the loaded drug in the optimized microspheres was evaluated in Wistar rats which showed an area under curve (AUC) almost 10 times higher than the pure drug.

[Studies on screening of matrix and permeation enhancer of sustained-release patches of duliang].

OBJECTIVE: To screen the matrix and permeation enhancer of Duliang Patches. METHODS: Based on L9 (3(4)) orthogonal experimental design, the content of imperatorin of the release rate and transdermal osmolality were regarded as evaluation indexes to optimize the matrix and permeation enhancer of patches suing of Drug dissolution tester and Franz diffusion cell. RESULTS: The best prescriplion of sustained-release patch of Duliang was: the quality percentage content of the starch, sodium carboxymethyl cellulose, glycerin, azone, propylene glycol and PEG400 was 6%, 2%, 30%, 1%, 15% and 2.5% respectively. The release behavior of sustained-release patches of Duliang tallied with Higuchi equation and the effect of sustained-release was apparent. CONCLUSION: The sustained-release patches of Duliang have good property of sustained-release and transdermal in vitro and the stability of patches is also sound while the release in vivo awaits further inspection.

Dietary fiber supplementation for fecal incontinence: a randomized clinical trial.

Dietary fiber supplements are used to manage fecal incontinence (FI), but little is known about the fiber type to recommend or the level of effectiveness of such supplements, which appears related to the fermentability of the fiber. The aim of this single-blind, randomized controlled trial was to compare the effects of three dietary fiber supplements (carboxymethylcellulose [CMC], gum arabic [GA], or psyllium) with differing levels of fermentability to a placebo in community-living individuals incontinent of loose/liquid feces. The primary outcome was FI frequency; secondary outcomes included FI amount and consistency, supplement intolerance, and quality of life (QoL). Possible mechanisms underlying supplement effects were also examined. After a 14-day baseline, 189 subjects consumed a placebo or 16 g total fiber/day of one of the fiber supplements for 32 days. FI frequency significantly decreased after psyllium supplementation versus placebo, in both intent-to-treat and per-protocol mixed model analyses. CMC increased FI frequency. In intent-to-treat analysis, the number of FI episodes/week after supplementation was estimated to be 5.5 for Placebo, 2.5 for Psyllium, 4.3 for GA, and 6.2 for CMC. Only psyllium consumption resulted in a gel in feces. Supplement intolerance was low. QoL scores did not differ among groups. Patients with FI may experience a reduction in FI frequency after psyllium supplementation, and decreased FI frequency has been shown to be an important personal goal of treatment for patients with FI. Formation of a gel in feces appears to be a mechanism by which residual psyllium improved FI.

Effects of an orabase formulation with ethanolic extract of Malva sylvestris L. in oral wound healing in rats.

Malva sylvestris L. is widely used in medicine for treatment of inflammatory processes. The plant has anti-inflammatory properties due to substances such as mucilage, flavonoids, and tannins. A mouthwash with leaves from the plant can be used for the treatment of wounds in the oral mucosa. The aim of this study was to assess the wound healing effect of Malva sylvestris L. on a palate mucosa wound in rats. After intraperitoneal anesthesia, a 4-mm-diameter excisional wound was made in the center of the palatal mucosa of 136 rats, using a punch-out biopsy tool. Eight animals were used as baseline wound. The remaining rats were divided into four groups: CO, control; OB, orabase vehicle; CX, 2% chlorhexidine; and MA, 20% Malva in orabase. At 24 h postoperatively, the animals were immobilized without anesthetic to apply 25 mg of each substance twice a day, totaling 50 mg daily. The wound areas were measured photographically and the reepithelialization rates were determined histologically (%) after 0, 3, 7, 15, and 21 days. The data were analyzed by ANOVA and Tukey post hoc test. Similar healing pattern was observed among the groups (P>.05; ANOVA). According to the methodology, Malva sylvestris L. extract had no effect on wound healing in the palatal mucosa of rats.

In vitro degradation and fermentation of three dietary fiber sources by human colonic bacteria.

Although clinical benefits of dietary fiber supplementation seem to depend partially on the extent of fiber degradation and fermentation by colonic bacteria, little is known about the effect of supplemental fiber type on bacterial metabolism. In an experiment using a nonadapted human bacterial population from three normal subjects, the extent of in vitro fermentation was greater for gum arabic (GA) than for psyllium (PSY), which was greater than that for carboxymethylcellulose (CMC). In a separate experiment, in vitro incubation with feces from 52 subjects with fecal incontinence, before and after random assignment to and consumption of one of three fiber (GA, PSY, or CMC) supplements or a placebo for 20-21 days, indicated that prior consumption of a specific fiber source did not increase its degradation by fecal bacteria. Results suggest that the colonic microbial community enriched on a particular fiber substrate can rapidly adapt to the presentation of a new fiber substrate. Clinical implications of the findings are that intake of a fiber source by humans is not expected to result in bacterial adaptation that would require continually larger and eventually intolerable amounts of fiber to achieve therapeutic benefits.

[Optimization of preparation technology of LIUWEI cataplasm, a kind of Zhuang national herbs].

OBJECTIVE: To optimize preparation process of liuwei cataplasm, a Zhuang folk medical herb popularly applied as a kind of rheumatism, rheumatoid drug in Guangxi Zhuang Autonomous Region. METHODS: Orthogonal design test was employed to optimise matrix proportion and molding technology of liuwei cataplasma with glossiness, adhesive power, matrix residue, skin following and repeatedly exposing as indexes. RESULTS: Optimum matrix ratio of PANA, pressure sensitive adhesive, CNC-Na, gelatin, dihydroxyaluminium aminoacetate and glycerol was 0.5:1.0:0.4:0.1:0.3:3.0. Optimized parameters of technology were as follows: stiring speed 600 r/min, refining temperature 60 degrees C and drug loading of Liuwei extract 13.04%. CONCLUSION: Optimized liuwei cataplasm has a good adhesive power, exipcients and glossiness, meanwhile drug loading is large and no skin residue. The process is simple, stable and viable.

Novel antiviral therapeutics to control foot-and-mouth disease.

Foot-and-mouth disease virus (FMDV) causes a highly contagious disease of cloven-hoofed animals. Vaccines require ∼7 days to induce protection; thus, before this time, vaccinated animals are still susceptible to the disease. Our group has previously shown that swine inoculated with 1×10(11) focus forming units (FFU) of a replication-defective human adenovirus containing the gene for porcine interferon alpha (Adt-pIFN-α) are sterilely protected from FMDV serotypes A24, O1 Manisa, or Asia 1 when the animals are challenged 1 day postadministration, and protection can last for 3-5 days. Polyriboinosinic-polyribocytidylic acid stabilized with poly-l-lysine and carboxymethyl cellulose (poly ICLC) is a synthetic double-stranded RNA that is a viral mimic and activates multiple innate immune pathways through interaction with toll-like receptor 3 and MDA-5. It is a potent inducer of IFNs. In this study, we initially examined the effect of poly IC and IFN-α on FMDV replication and gene induction in cell culture. Poly ICLC alone or combined with Adt-pIFN-α was then evaluated for its therapeutic efficacy in swine against intradermal challenge with FMDV A24, 1 day post-treatment. Groups of swine were subcutaneously inoculated either with poly ICLC alone (4 or 8 mg) or in combination with different doses of Adt-pIFN-α (2.5×10(9), 1×10(9), or 2.5×10(8) FFU). While different degrees of protection were achieved in all the treated animals, a dose of 8 mg of poly ICLC alone or combined with 1×10(9) FFU of Adt-pIFN-α was sufficient to sterilely protect swine when challenged 24 h later with FMDV A24. IFN-stimulated gene (ISG) expression in peripheral blood mononuclear cells at 1 day post-treatment was broader and higher in protected animals than in nonprotected animals. These data indicate that poly ICLC is a potent stimulator of IFN and ISGs in swine and at an adequate dose is sufficient to induce complete protection against FMD.

Postoperative adhesion prevention using a statin-containing cellulose film in an experimental model.

BACKGROUND: Intraperitoneal adhesions are a common problem in abdominal surgery. The aim of this study was to compare the effectiveness of Statofilm, a novel antiadhesive film based on cross-linked carboxymethylcellulose and atorvastatin, with that of sodium hyaluronate-carboxymethylcellulose (Seprafilm(®)) in the prevention of postoperative intraperitoneal adhesions in rats. METHODS: One hundred male Wistar rats underwent a laparotomy and adhesions were induced by caecal abrasion. The animals were allocated to five groups: a control group with no adhesion barrier, Seprafilm(®) group, placebo group with a film containing carboxymethylcellulose without atorvastatin, and low- and high-dose groups with films containing carboxymethylcellulose and atorvastatin 0·125 and 1 mg per kg bodyweight respectively. Adhesions were classified by two independent surgeons 2 weeks after surgery. Caecal biopsies were obtained for histological evaluation of fibrosis, inflammation and vascular proliferation. RESULTS: All antiadhesive film groups (Seprafilm(®), placebo, low-dose and high-dose) had statistically significant adhesion reduction compared with the control group (P < 0·001, P = 0·015, P < 0·001 and P < 0·001 respectively). The low-dose Statofilm was superior to Seprafilm(®) in terms of adhesion prevention (P = 0·001). Adhesions were present in three-quarters of rats in the Seprafilm(®) group, but only one-quarter in the low-dose Statofilm group. CONCLUSION: The data suggest that the newly developed adhesion barrier Statofilm has better results than Seprafilm(®) in preventing postoperative adhesions in rats. A low-dose atorvastatin-containing film, such as Statofilm, could be evaluated for future clinical application.

Randomized, phase III study comparing osmoprotective carboxymethylcellulose with sodium hyaluronate in dry eye disease.

PURPOSE: To compare a treatment containing carboxymethylcellulose (CMC) and the osmoprotective (OsPr) compatible osmolytes erythritol, L-carnitine, and glycerin (OsPr-CMC) with a standard sodium hyaluronate (Na-HY) formulation in patients with dry eye disease. METHODS: This was a 3-month, phase III, noninferiority study. Patients were randomized 1:1 to receive OsPr-CMC (OPTIVE®) or Na-HY (VISMED®). The primary efficacy outcome was the mean change from baseline in total ocular staining at day 35, scored using the 15-point Oxford scale. Noninferiority was assessed using the adjusted means. The secondary efficacy outcome was change in ocular surface disease index (OSDI) score from baseline to day 35. Other outcomes included tear osmolarity, Schirmer-I test score, OSDI, ease of use, patient acceptability, tolerability, and safety. RESULTS: A total of 82 patients were randomized. The primary efficacy analysis was per protocol (OsPr-CMC, n=37; Na-HY, n=29). OsPr-CMC was noninferior to Na-HY in terms of adjusted mean change (SE) in ocular staining score at day 35: -2.0 (0.33) with OsPr-CMC vs -1.7 (0.37) with Na-HY. Similar improvements were seen in tear osmolarity, Schirmer-I test score, OSDI, and ocular staining for OsPr-CMC and Na-HY. More patients treated with OsPr-CMC vs Na-HY liked using their eyedrops, reported that their eyes felt comfortable, and found the treatment easy to use. Both treatments were well tolerated, with no serious treatment-related adverse events. CONCLUSIONS: Compared with Na-HY, OsPr-CMC was noninferior in terms of efficacy and safety, preferred by patients, and easier to use. Osmoprotection using OsPr-CMC therefore represents a viable option for dry eye disease management.

[Preparation and pharmacokinetics of brucine hydrogel patch].

OBJECTIVE: To investigate the effect of dose on pharmacokinetic properties of brucine hydrogel patch. METHODS: The plasma concentration of brucine was determined by HPLC. Brucine hydrogel patch was prepared and its pharmaceutical characterization was investigated. After transdermal administration of different dose brucine hydrogel patch; Plasma concentration versus time profiles were determined and pharmacokinetic parameters were calculated by DAS program. RESULTS: The pharmaceutical properties of brucine hydrogel patch were satisfactory. The AUC0-1 values were 7.24 +/- 0.61, 16.02 +/- 2.34 and 54.84 +/- 26.59 microg x h/mL after administration of 30, 60 and 180 mg/kg brucine hydrogel patch, respectively. The corresponding C(max) values were 0.73 +/- 0.23, 1.45 +/- 0.28 and 4.59 +/- 1.85 microg/mL, respectively. And the corresponding T(max) values were 8.67 +/- 2.07, 11.67 +/- 2.66 and 8.33 +/- 2.65 h, respectively. CONCLUSION: The pharmacokinetic properties of brucine do not vary with the dose of brucine hydrogel patch.

Imaging assessment of the modified double contrast barium enema using carboxymethylcellulose on radiography and ultrasonography in dogs.

A modified double contrast barium enema using carboxymethylcellulose was evaluated in beagle dogs and compared with dogs receiving a conventional barium enema. The experimental group was divided into three groups (1, 2, and 3) and given 30 ml/kg of different volume ratios of a barium vs. carboxymethylcellulose mixture. Each group underwent sonography following radiography. The volume ratio of one part barium to three parts carboxymethylcellulose was judged to be the optimal mixture, resulting in a general distribution of contrast and bowel radiolucency on radiographs and adequate postradiography sonography. The modified barium enema using carboxymethylcellulose is useful for assessing the general morphology and mucosal layers of the colon simultaneously on radiographs and ultrasonographs.

Topical application of glycyrrhizin preparation ameliorates experimentally induced colitis in rats.

AIM: To examine the efficacy of glycyrrhizin preparation (GL-p) in the treatment of a rat model of ulcerative colitis (UC). METHODS: Experimental colitis was induced by oral administration of dextran sodium sulfate. Rats with colitis were intrarectally administered GL-p or saline. The extent of colitis was evaluated based on body weight gain, colon wet weight, and macroscopic damage score. The expression levels of pro-inflammatory cytokines and chemokines in the inflamed mucosa were measured by cytokine antibody array analysis. The effect of GL-p on myeloperoxidase (MPO) activity in the inflamed mucosa and purified enzyme was assayed. RESULTS: GL-p treatment significantly ameliorated the extent of colitis compared to sham treatment with saline. Cytokine antibody array analysis showed that GL-p treatment significantly decreased the expression levels of pro-inflammatory cytokines and chemokines, including interleukin (IL)-1ß, IL-6, tumor necrosis factor-α, cytokine-induced neutrophil chemoattractant-2, and monocyte chemoattractant protein-1 in the inflamed mucosa. Furthermore, GL-p inhibited the oxidative activity of mucosal and purified MPO. CONCLUSION: GL-p enema has a therapeutic effect on experimental colitis in rats and may be useful in the treatment of UC.

Wound healing evaluation of sodium fucidate-loaded polyvinylalcohol/sodium carboxymethylcellulose-based wound dressing.

The cross-linked hydrogel films containing sodium fucidate were previously reported to be prepared polyvinyl alcohol (PVA) and sodium carboxymethylcellulose (Na-CMC) using the freeze-thawing method and their physicochemical property was investigated. For the development of novel sodium fucidate-loaded wound dressing, here its in vivo wound healing test and histopathology were performed compared with the conventional ointment product. In wound healing test, the sodium fucidate-loaded composed of 2.5% PVA, 1.125% Na-CMC and 0.2% drug showed faster healing of the wound made in rat dorsum than the hydrogel without drug, indicating the potential healing effect of sodium fucidate. Furthermore, from the histological examination, the healing effect of sodium fucidate-loaded hydrogel was greater than that of the conventional ointment product and hydrogel without drug, since it might gave an adequate level of moisture and build up the exudates on the wound area. Thus, the sodium fucidate-loaded wound dressing composed of 5% PVA, 1.125% Na-CMC and 0.2% drug is a potential wound dressing with excellent wound healing.

[Study on formulation of naoxuekang dispersible tablets].

OBJECTIVE: To study the formulation of Naoxuekang dispersible tablets. METHODS: The formulation was determined by pre-processing leech extractum prior to a series of experiments used to screen excipients like bulking agents and disintegrants and so on, and by adding disintegrants within and without. RESULTS: Microcrystalline cellulose was determined as the bulking agent, and carboxymethyl cellulose and low-substituted hydroxypropyl cellulose were determined as the disintegrants of Naoxuekang dispersible tablet formula. The average disintegration time and nitrogen content of one tablet were 52 seconds and 5.47 milligrams, respectively. Also disperse homogeneity, weight variation and microbial limit all met the requirements in Ch. P. CONCLUSION: The prepared Naoxuekang dispersible tablet is reasonable in formula, feasible in technology, which meets the quality standards.

Preventing intraperitoneal adhesions with vitamin E and sodium hyaluronate/carboxymethylcellulose: a comparative study in rats.

PURPOSE: To compare the effectiveness of intraperitoneally administered vitamin E with the sodium hyaluronate/carboxymethylcellulose membrane (HA/CBMC) in preventing postoperative intraperitoneal adhesion formation. METHODS: Sixty Wistar rats underwent a laparotomy and adhesions were induced (IA). The animals were divided into four groups: group 1, control (IA); group 2 (IA + Vitamin E): group 3 (IA+HA/CBMC) and group 4 (IA+ Vitamin E + HA/CBMC). The Vitamin E (groups 2 and 4) and HA/CBMC (groups 3 and 4) were administered intraperitoneally before the abdominal wall was closed. After 30 days, adhesions were classified by an independent surgeon. RESULTS: Three animals died; one from group 3 and two from group 4. All control animals had substantial adhesions compared with unsubstantial adhesions observed in 11/15 in group 2 (P = 0.000), 11/14 in group 3 (P = 0.001), and 10/13 in group 4 (P = 0.000). CONCLUSION: Vitamin E, administered intraperitoneally, is as effective as HA/CBMC in preventing postoperative adhesions.

Preventing intraperitoneal adhesions with vitamin E and sodium hyaluronate/carboxymethylcellulose: a comparative study in rats

PURPOSE: To compare the effectiveness of intraperitoneally administered vitamin E with the sodium hyaluronate/carboxymethylcellulose membrane (HA/CBMC) in preventing postoperative intraperitoneal adhesion formation. METHODS: Sixty Wistar rats underwent a laparotomy and adhesions were induced (IA). The animals were divided into four groups: group 1, control (IA); group 2 (IA + Vitamin E): group 3 (IA+HA/CBMC) and group 4 (IA+ Vitamin E + HA/CBMC). The Vitamin E (groups 2 and 4) and HA/CBMC (groups 3 and 4) were administered intraperitoneally before the abdominal wall was closed. After 30 days, adhesions were classified by an independent surgeon. RESULTS: Three animals died; one from group 3 and two from group 4. All control animals had substantial adhesions compared with unsubstantial adhesions observed in 11/15 in group 2 (P = 0.000), 11/14 in group 3 (P = 0.001), and 10/13 in group 4 (P = 0.000). CONCLUSION: Vitamin E, administered intraperitoneally, is as effective as HA/CBMC in preventing postoperative adhesions.

OBJETIVO: Comparar a efetividade da Vitamina E e da membrana de Carboximetilcelulose/Hialuronato de Sódio (CBMC/HA) na prevenção da formação de aderências intraperitoneais pós-operatórias. MÉTODOS: Sessenta ratos Wistar foram submetidos à laparotomia para indução de aderências (IA) com abrasão do ceco seguido de aplicação de álcool absoluto e sutura com fio de seda no peritônio parietal. Os animais foram divididos em quatro grupos: 1 controle ( IA ); 2 ( IA + Vitamina E ); 3( IA + CBMC/HA ) e 4 ( IA + Vitamina E + CBMC/HA ). A Vitamina E ( grupos 2 e 4 ) e CBMC/HA ( grupos 3 e 4 ) foram administrados intraperitonealmente antes do fechamento da parede. Os ratos foram sacrificados em 30 dias e as aderências foram classificadas por cirurgião independente. Resultados: Três animais morreram, sendo um do grupo 3 e dois do grupo 4. Todos os animais do grupo controle ( 1 ) tiveram aderências substanciais, comparados com aderências insubstanciais em 11/15 no grupo 2 ( p = 0,000 ), 11/14 no grupo 3 ( p = 0,001 ) e 10/13 no grupo 4 ( p = 0,000 ). CONCLUSÃO: A Vitamina E administrada de maneira intraperitoneal é tão eficaz quanto a CBMC/HA na prevenção da formação de aderências pós-operatórias.

Effect of various calcium/phosphates ratios of carboxymethylcellulose-based saliva substitutes on mineral loss of bovine enamel in vitro.

OBJECTIVES: The present study evaluated the effects of various calcium and phosphate concentrations and ratios of carboxymethylcellulose (CMC)-based solutions on the mineral loss of predemineralised bovine enamel in vitro. METHODS: Bovine enamel specimens were prepared, polished and partly covered with nail varnish, thus serving as control of sound enamel. After demineralisation (37 degrees C; pH 5.0; 14 days) the specimens were exposed to CMC-based solutions (20g/l) with various saturations with respect to apatites containing 0.1mM NaF, CaCl2 (0-32 mM) and KH2PO4 (0-52 mM) at two different pH values (5.5 or 6.5). A fluoride-free solution served as control, and four commercially available products were tested as well. The differences in mineral loss (DeltaDeltaZ) between the values prior to (DeltaZ Demin) and after storage (DeltaZ Effect) in the various solutions were evaluated from microradiographs of thin sections (100microm). RESULTS: The general linear model revealed a significant dependency for DeltaDeltaZ on 'calcium' (p<0.001), 'phosphate' (p=0.023), 'fluoride' (p=0.002) and 'pH' (p<0.001). With increasing calcium and phosphate concentrations an increase in DeltaDeltaZ could be observed up to the solution containing the third highest saturation with respect to octacalciumphosphate (3.2), showing a significant remineralisation (p<0.05; t-test). The commercially available products as well as the control groups revealed significantly reduced DeltaDeltaZ values compared to this group (p<0.01; Bonferroni). CONCLUSIONS: A saturation with respect to octacalciumphosphate of 3.2 and a pH of 6.5 enables CMC-based solutions to remineralise bovine enamel in vitro.

Novel dry powder preparations of whole inactivated influenza virus for nasal vaccination.

The purpose of these studies was to enhance mucosal and systemic antibody production in response to increased local residence time of a whole inactivated influenza virus administered as a dry powder nasal vaccine formulation. Spray-freeze-drying (SFD) particles suitable for nasal delivery were characterized for physico-chemical properties and stability. Mucoadhesive compounds (MA) were characterized for their effects on nasal residence time of vaccine powders in rats compared with published in vitro data and elicited immune responses. SFD particles (D(50) = 26.9 microm) were spherical with a specific surface area of 1.25 m(2)/g. Thermal analysis indicated SFD powders were amorphous and demonstrated improved stability with respect to liquid formulations under various storage conditions. In vitro physico-chemical studies and in vivo scintigraphic imaging experiments indicated sodium alginate (SA) and carboxymethylcellulose-high molecular weight (CMC-HMW) powder formulations most significantly increased residence time in Brown Norway rats. Intramuscular delivery provided equivalent serum antibody titers to intranasal (IN) powder without MA, in the presence of CMC-HMW, SA, and hydroxypropyl methylcellulose (HPMC-HMW) after initial dosing and all formulations except IN powder with chitosan after boosting. IN liquid provided equivalent serum antibody titers to all IN powders after the initial vaccination and significantly greater serum antibody titers than IN powder with chitosan after boosting. Trends were consistent between residence time studies and immune response; however, no statistically significant differences between powder and liquid formulations were observed. It was concluded that enhanced serum and mucosal antibody responses were elicited by a dry powder nasal vaccine, specifically, administered in the presence of sodium alginate.