RESUMEN
Dental caries remains a world-wide disease despite the global distribution of fluoride. It has become apparent that the introduction of significant levels of sugar (fermentable carbohydrate) into the diet has resulted in a change in the biofilm, encouraging acid formation. Further, there has been a shift in the microbiota in the biofilm to a flora that produces acid, and thrives and reproduces in an acidic environment. The management of caries activity under these conditions has focused on brushing to remove the biofilm with fluoride pastes, and high-dose fluoride treatments. Kleinberg, in the 1970s, identified an arginine-containing compound in saliva that several oral biofilm bacterial species metabolize to produce base. Multiple in situ and in vivo studies have been conducted, and have discussed the ability of multiple bacteria to increase the resting pH of the biofilm and even reduce the decrease in pH when the biofilm is challenged with glucose. This shift in resting pH can shift the level of caries formation by the biofilm. Here, we present 8 clinical studies, with different clinical designs, measuring different clinical outcomes, for a diverse, world-wide population. Each of these studies demonstrates reductions in caries formation beyond that seen with fluoride alone and several demonstrate the reversal of early caries lesions. Significant clinical research has been shown that 1.5% arginine combined with fluoride toothpaste has superior anti-caries efficacy to toothpaste containing fluoride alone.
Asunto(s)
Arginina/farmacología , Biopelículas/efectos de los fármacos , Cariostáticos/química , Cariostáticos/farmacología , Fluoruros Tópicos/farmacología , Pastas de Dientes/química , Pastas de Dientes/farmacología , Amoníaco/metabolismo , Placa Dental/microbiología , Humanos , Concentración de Iones de Hidrógeno , Lactatos/metabolismoRESUMEN
Infection with equine herpesvirus-1 (EHV-1) causes respiratory disease, late-term abortions and equine herpesvirus myeloencephalitis (EHM). Our understanding of EHM pathogenesis is limited except for the knowledge that EHV-1 infected, circulating peripheral blood mononuclear cells (PBMC) transport virus to the central nervous system vasculature causing endothelial cell infection leading to development of EHM. Our objective was to develop a model of CNS endothelial cell infection using EHV-1 infected, autologous PBMC. PBMCs, carotid artery and brain endothelial cells (EC) from 14 horses were harvested and grown to confluency. PBMC or ConA-stimulated PBMCs (ConA-PBMCs) were infected with EHV-1, and sedimented directly onto EC monolayers ('contact'), or placed in inserts on a porous membrane above the EC monolayer ('no contact'). Cells were cultured in medium with or without EHV-1 virus neutralizing antibody. Viral infection of ECs was detected by cytopathic effect. Both brain and carotid artery ECs became infected when cultured with EHV-1 infected PBMCs or ConA-PBMCs, either in direct contact or no contact: infection was higher in carotid artery than in brain ECs, and when using ConA-PBMCs compared to PBMCs. Virus neutralizing antibody eliminated infection of ECs in the no contact model only. This was consistent with cell-to-cell spread of EHV-1 infection from leucocytes to ECs, demonstrating the importance of this mode of infection in the presence of antibody, and the utility of this model for study of cellular interactions in EHV-1 infection of ECs.
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Células Endoteliales/virología , Infecciones por Herpesviridae/veterinaria , Herpesvirus Équido 1/patogenicidad , Caballos/virología , Animales , Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/inmunología , Encéfalo/citología , Arterias Carótidas/citología , Células Cultivadas , Sistema Nervioso Central/citología , Células Endoteliales/patología , Infecciones por Herpesviridae/inmunología , Infecciones por Herpesviridae/virología , Herpesvirus Équido 1/inmunología , Enfermedades de los Caballos/inmunología , Enfermedades de los Caballos/patología , Enfermedades de los Caballos/virología , Leucocitos Mononucleares/patología , Leucocitos Mononucleares/virologíaRESUMEN
The aim of this study was to evaluate the reproductive performance of gilts that had a similar age but different weights at the onset of puberty stimulation by boar exposure at 144 days. Gilts were divided into two groups according to their lifetime growth rate from birth to approximately 144 days of age. Mean growth rates at this moment were 577 and 724 g/day for group 1 (G1; n = 58) and group 2 (G2; n = 58), respectively. After selection, gilts were weighed at approximately 155, 165 and 175 days of age, on the insemination day and at slaughter. Gilts were inseminated, on average, at 193 days of age and were slaughtered 32 days after insemination, when the number of corpora lutea and embryos were recorded. Higher growth rate gilts (G2) reached puberty earlier (155.3 vs 164.1 days; p < 0.01). More gilts of G2 group attained puberty by 190 days of age (p = 0.004) than G1 gilts (95%; 55/58 vs 76%; 44/58). The anoestrous rate, until 60 days after the onset of boar exposure was higher (p < 0.01) in G1 (19.0%; 11/58) than in G2 (3.4%; 2/58) group. However, there were no differences in the pregnancy rate (90.7 vs 94.5), ovulation rate (15.9 vs 16.5), total embryos (12.9 vs 11.7), viable embryos (12.0 vs 11.1) and embryo survival (73.7% vs 68.5%), between G1 gilts and G2 gilts, respectively (p > 0.05). High growth rate gilts attain puberty earlier and have a lower anoestrous rate than low growth rate gilts.
Asunto(s)
Reproducción/fisiología , Maduración Sexual/fisiología , Porcinos/crecimiento & desarrollo , Tejido Adiposo/anatomía & histología , Envejecimiento , Anestro/fisiología , Animales , Peso Corporal , Pérdida del Embrión/epidemiología , Pérdida del Embrión/veterinaria , Desarrollo Embrionario , Femenino , Inseminación Artificial , Masculino , Ovulación , Embarazo , Índice de Embarazo , Análisis de Regresión , Porcinos/anatomía & histología , Porcinos/fisiologíaRESUMEN
UNLABELLED: The Red Queen said, 'It takes all the running you can do, to keep in the same place.' Lewis Carrol MOTIVATION: Newly solved protein structures are routinely scanned against structures already in the Protein Data Bank (PDB) using Internet servers. In favourable cases, comparing 3D structures may reveal biologically interesting similarities that are not detectable by comparing sequences. The number of known structures continues to grow exponentially. Sensitive-thorough but slow-search algorithms are challenged to deliver results in a reasonable time, as there are now more structures in the PDB than seconds in a day. The brute-force solution would be to distribute the individual comparisons on a massively parallel computer. A frugal solution, as implemented in the Dali server, is to reduce the total computational cost by pruning search space using prior knowledge about the distribution of structures in fold space. This note reports paradigm revisions that enable maintaining such a knowledge base up-to-date on a PC. AVAILABILITY: The Dali server for protein structure database searching at http://ekhidna.biocenter.helsinki.fi/dali_server is running DaliLite v.3. The software can be downloaded for academic use from http://ekhidna.biocenter.helsinki.fi/dali_lite/downloads/v3.
Asunto(s)
Bases de Datos de Proteínas , Proteínas/química , Programas Informáticos , Algoritmos , Internet , Análisis de Secuencia de ProteínaRESUMEN
Platelet/endothelial cell adhesion molecule-1 (PECAM-1, CD31), expressed on the surfaces of leukocytes and concentrated in the junctions between endothelial cells plays an important role in transendothelial migration of neutrophils and monocytes. Soluble recombinant PECAM-IgG injected i.v. into mice blocks acute leukocyte emigration by 80%. To study the role of PECAM in models of chronic inflammation, we generated transgenic mice constitutively expressing soluble full-length murine PECAM as an IgG chimera. Three founder lines expressed this transgene and constitutively secreted murine PECAM-IgG into the plasma where it was maintained at characteristic concentrations for each line. All mice had similar hematologic profiles to wild-type littermates and were healthy when maintained in the standard laboratory animal facility. Both the leukocytes and the endothelium of mice of all transgenic lines expressed the same levels of endogenous PECAM-1 as wild-type littermates. Similarly, there were no detectable differences in the expression of several other common leukocyte and endothelial cell adhesion molecules. Mice that produced moderate (10-20 microg/ml) concentrations of PECAM-IgG demonstrated a severely blunted acute inflammatory response, despite mobilizing appropriate numbers of circulating leukocytes. Surprisingly, mice that constitutively produced high (400-1,000 microg/ml) concentrations of PECAM-IgG were unresponsive to its anti-inflammatory effects. This is the first demonstration that a soluble form of a cell adhesion molecule can be stably expressed and retain efficacy in vivo over prolonged periods. This approach is applicable to many other extracellular molecules. However, the plasma concentrations of such constitutively produced inhibitors may greatly influence the resulting phenotype.
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Inmunoglobulina G/biosíntesis , Inmunoglobulina G/genética , Peritonitis/inmunología , Molécula-1 de Adhesión Celular Endotelial de Plaqueta/biosíntesis , Molécula-1 de Adhesión Celular Endotelial de Plaqueta/genética , Animales , Antiinflamatorios no Esteroideos/farmacología , Enfermedad Crónica , Cruzamientos Genéticos , Relación Dosis-Respuesta Inmunológica , Humanos , Inmunoglobulina G/sangre , Inyecciones Intraperitoneales , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos , Ratones Transgénicos , Peritonitis/genética , Peritonitis/prevención & control , Fenotipo , Molécula-1 de Adhesión Celular Endotelial de Plaqueta/sangre , Molécula-1 de Adhesión Celular Endotelial de Plaqueta/fisiología , Proteínas Recombinantes de Fusión/administración & dosificación , Proteínas Recombinantes de Fusión/sangre , Proteínas Recombinantes de Fusión/genética , Solubilidad , Tioglicolatos/administración & dosificaciónRESUMEN
The present study was performed to assess dose-response relationships of local botulinum toxin A (BtxA) treatment in children and teenagers with spastic gait due to cerebral palsy (CP) in a randomized, double-blind study employing a "high-dose" (200 units Botox per leg) and a "low-dose" (100 units Botox per leg) treatment arm in 33 patients with CP. Response parameters included changes in muscle tone assessed by the Ashworth scale at knee joint, range-of-motion (ROM) measurements at knee and ankle joint, objective analysis of longitudinal gait parameters as well as subjective assessments of improvement. Patients in the "high-dose" arm received 40-80 units Botox/muscle versus 20-40 units Botox/muscle in the "low-dose" group. Patients in both treatment arms showed significant improvement of Ashworth score (p<0.001) and ROM (p<0.01), while gait analysis revealed significant increase in gait velocity (p<0.01) and stride-length (p<0.001) over baseline. Subjects in the "high-dose" group showed significantly greater improvement on objective response measurements compared to "low-dose" patients. Also, children aged 7 years or less had greater functional benefit compared to the subgroup of patients older than 7 years. Incidence and severity of side-effects were similar in both treatment groups. The present study demonstrated dose-dependent functional improvement of dynamic deformities and spastic gait pattern in children and young adults with CP treated with local injections of botulinum toxin. A dose of 200 units Botox per leg distributed to 4 or 5 muscle bellies per leg is superior compared to 100 units Botox per leg without significantly affecting the risk of side-effects.
Asunto(s)
Toxinas Botulínicas Tipo A/administración & dosificación , Parálisis Cerebral/tratamiento farmacológico , Marcha/efectos de los fármacos , Espasticidad Muscular/tratamiento farmacológico , Adolescente , Adulto , Toxinas Botulínicas Tipo A/efectos adversos , Parálisis Cerebral/diagnóstico , Niño , Preescolar , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Femenino , Humanos , Inyecciones Intramusculares , Masculino , Espasticidad Muscular/diagnósticoRESUMEN
Declining blood CD4(+) T-cell counts mark the progress of simian immunodeficiency virus (SIV) disease in macaques and model the consequences of untreated human immunodeficiency virus infection in humans. However, blood lymphocytes are only a fraction of the recirculating lymphocyte pool, and their numbers are affected by cell synthesis, cell depletion, and distribution among blood and lymphoid tissue compartments. Asymptomatic, SIV-infected macaques maintained constant and nearly normal numbers of recirculating lymphocytes despite the decline in CD4(+) T-cell counts. Substantial depletion was detected only when blood CD4(+) T-cell counts fell below 300/microliter. In asymptomatic animals, changes in CD4(+) T-cell distribution were more important than lymphocyte depletion for controlling the blood cell levels.
Asunto(s)
Recuento de Linfocito CD4 , Tejido Linfoide/patología , Síndrome de Inmunodeficiencia Adquirida del Simio/inmunología , Animales , Relación CD4-CD8 , Ganglios Linfáticos/patología , Macaca mulatta , Síndrome de Inmunodeficiencia Adquirida del Simio/patologíaRESUMEN
Pertussis toxin treatment in macaques inhibits lymphocyte extravasation from the blood and leads to transient lymphocytosis and leukocytosis. We examined lymphocyte adhesion molecules known to be involved in the extravasation process to find possible mechanisms for the effects of pertussis toxin treatment. The two subunits of LFA-1, CD11a and CD18, showed decreased surface expression on lymphocytes from pertussis toxin treated animals compared to untreated animals. The adhesion molecule CD44, and the alpha subunit of the integrin VLA-4 (CD49d) were not decreased by pertussis toxin treatment. Lower surface expression of CD11a and CD18 was observed on all lymphocyte subsets and was correlated inversely with the extent of lymphocytosis. The magnitude of lymphocytosis after pertussis toxin treatment was higher in SIV-infected macaques than in uninfected animals. However, changes in LFA-1 levels were similar in both groups. These data show that LFA-1 surface levels are affected by pertussis toxin in vivo and this change may account in part, for the ability of pertussis toxin to induce lymphocytosis.
Asunto(s)
Antígeno-1 Asociado a Función de Linfocito/biosíntesis , Linfocitos/inmunología , Toxina del Pertussis , Síndrome de Inmunodeficiencia Adquirida del Simio/inmunología , Factores de Virulencia de Bordetella/farmacología , Animales , Antígenos CD20/metabolismo , Antígenos CD18/biosíntesis , Linfocitos T CD4-Positivos/metabolismo , Linfocitos T CD8-positivos/metabolismo , Recuento de Células/efectos de los fármacos , Citometría de Flujo , Expresión Génica/efectos de los fármacos , Antígeno-1 Asociado a Función de Linfocito/genética , Linfocitos/efectos de los fármacos , Linfocitosis , Macaca mulatta , Factores de TiempoRESUMEN
This case report presents a patient with painful legs and moving toes on the right side followed by the development of involuntary movements in his right hand. The frequencies of the semirhythmic muscle activities in both extremities were different. This finding excludes one central pacemaker for both and supports the notion that separate oscillators in the segmental interneuron pool of different spinal areas may drive the individual movements in this case.
Asunto(s)
Enfermedades del Sistema Nervioso Periférico/fisiopatología , Síndrome de las Piernas Inquietas/fisiopatología , Electromiografía , Dedos/inervación , Humanos , Pierna/inervación , Masculino , Persona de Mediana Edad , Enfermedades Neuromusculares/fisiopatología , Dolor Intratable , Síndrome , Dedos del Pie/inervaciónRESUMEN
The gastric mucosa is an important portal of entry for lymphocytic choriomeningitis virus (LCMV) infections. Within hours after intragastric (i.g.) inoculation, virus appears in the gastric epithelia, then in the mesenteric lymph nodes and spleen, and then in the liver and brain. By 72 h i.g.-inoculated virus is widely disseminated and equivalent to intravenous (i.v.) infection (S. K. Rai, B. K. Micales, M. S. Wu, D. S. Cheung, T. D. Pugh, G. E. Lyons, and M. S. Salvato. Am. J. Pathol. 151:633-639, 1997). Pretreatment of mice with a G protein inhibitor, pertussis toxin (PTx), delays LCMV dissemination after i.g., but not after i.v., inoculation. Delayed infection was confirmed by plaque assays, by reverse transcription-PCR, and by in situ hybridization. The differential PTx effect on i.v. and i.g. infections indicates that dissemination from the gastric mucosa requires signals transduced through heterotrimeric G protein complexes. PTx has no direct effect on LCMV replication, but it modulates integrin expression in part by blocking chemokine signals. LCMV infection of macrophages up-regulates CD11a, and PTx treatment counteracts this. PTx may prevent early LCMV dissemination by inhibiting the G protein-coupled chemotactic response of macrophages infected during the initial exposure, thus blocking systemic virus spread.
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Proteínas de Unión al GTP/fisiología , Mucosa Gástrica/virología , Coriomeningitis Linfocítica/etiología , Virus de la Coriomeningitis Linfocítica/patogenicidad , Animales , Moléculas de Adhesión Celular/metabolismo , Células Cultivadas , Quimiotaxis/efectos de los fármacos , Cartilla de ADN/genética , Hibridación in Situ , Inyecciones Intravenosas , Coriomeningitis Linfocítica/fisiopatología , Coriomeningitis Linfocítica/virología , Virus de la Coriomeningitis Linfocítica/genética , Virus de la Coriomeningitis Linfocítica/fisiología , Macrófagos/efectos de los fármacos , Macrófagos/fisiología , Macrófagos/virología , Masculino , Ratones , Ratones Endogámicos BALB C , Especificidad de Órganos , Toxina del Pertussis , Transducción de Señal , Factores de Tiempo , Factores de Virulencia de Bordetella/farmacología , Replicación ViralRESUMEN
Anti-neutrophil cytoplasmic antibodies (ANCAs) targeting proteinase 3 (PR3) have a high specifity for Wegener's granulomatosis (WG), and their role in activating leukocytes is well appreciated. In this study, we investigated the influence of PR3-ANCA and murine monoclonal antibodies on human umbilical vascular endothelial cells (HUVECs). Priming of HUVECs with tumor necrosis factor alpha induced endothelial upregulation of PR3 message and surface expression of this antigen, as measured by Cyto-ELISA, with a maximum occurrence after 2 h. Primed cells responded to low concentrations of both antibodies (25 ng-2.5 microg/ml), but not to control immunoglobulins, with pronounced, dose-dependent phosphoinositide hydrolysis, as assessed by accumulation of inositol phosphates. The signaling response peaked after 20 min, in parallel with the appearance of marked prostacyclin and platelet-activating factor synthesis. The F(ab)2 fragment of ANCA was equally potent as ANCA itself. Disrupture of the endothelial F-actin content by botulinum C2 toxin to avoid antigen-antibody internalization did not affect the response. In addition to the metabolic events, anti-PR3 challenge, in the absence of plasma components, provoked delayed, dose-dependent increase in transendothelial protein leakage. We conclude that anti-PR3 antibodies are potent inductors of the preformed phosphoinositide hydrolysis-related signal tranduction pathway in human endothelial cells. Associated metabolic events and the loss of endothelial barrier properties suggest that anti-PR3-induced activation of endothelial cells may contribute to the pathogenetic sequelae of autoimmune vasculitis characterizing WG.
Asunto(s)
Anticuerpos Anticitoplasma de Neutrófilos/inmunología , Anticuerpos Monoclonales/inmunología , Endotelio Vascular/inmunología , Granulomatosis con Poliangitis/inmunología , Serina Endopeptidasas/inmunología , Transducción de Señal , Comunicación Celular , Células Cultivadas , Selectina E/metabolismo , Endotelio Vascular/efectos de los fármacos , Endotelio Vascular/patología , Ensayo de Inmunoadsorción Enzimática , Granulomatosis con Poliangitis/patología , Humanos , Mieloblastina , Fosfatidilinositoles/metabolismo , Factor de Activación Plaquetaria/metabolismo , Reacción en Cadena de la Polimerasa , Factor de Necrosis Tumoral alfa/farmacología , Molécula 1 de Adhesión Celular Vascular/metabolismoRESUMEN
Therapeutic effect of botulinum toxin A was studied in a group of pediatric patients (n = 28) aged between 6 months and 18 years. The patients were diagnosed with cervical dystonia (n = 6), adductor spasm of the hip (n = 8), spastic drop foot (n = 7) and various other focal motor problems associated with spastic muscular hyperactivity (n = 7). The mean dose of botulinum toxin A (Dysport) used to inject into the affected muscle was 22 U/kg body weight. Reduced muscular hyperactivity with a significant increase in joint mobility was achieved for dystonic (p < 0.0001) as well as for spastic conditions in patients with adductor spasm (p < 0.0002). For these patients the improved joint mobility represented a significant benefit for both daily activities and nursing care. Local paresis and local hematoma were observed in 1/28 and 1/28 patients, respectively; 1/28 patients developed a secondary non-response. However, apart from these side effects, no other adverse reactions to botulinum toxin A treatment were recorded during the treatment and observation period (12-64 months). Our results suggest that botulinum toxin A represents an effective and safe therapeutic substance for the treatment of pediatric patients suffering of focal motor problems due to dystonic or spastic muscular hyperactivity.
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Toxinas Botulínicas Tipo A/uso terapéutico , Distonía/tratamiento farmacológico , Espasticidad Muscular/tratamiento farmacológico , Neurología , Fármacos Neuromusculares/uso terapéutico , Pediatría , Adolescente , Niño , Preescolar , Relación Dosis-Respuesta a Droga , Distonía/diagnóstico , Electromiografía , Femenino , Humanos , Lactante , Masculino , Espasticidad Muscular/diagnóstico , Músculo Esquelético/inervación , Índice de Severidad de la EnfermedadRESUMEN
The objective of this prospective study was to evaluate the intra- and postoperative pain in vitreoretinal surgery under retrobulbar anesthesia (RBA) in 53 patients, considering objective stress parameters such as blood pressure, heart rate and plasma concentration of cortisol (PCC). The level of pain was graded on a standard 4-point nominal scale. Mean pain score after RBA was 1.04, decreased perioperative to 0.77, and increased again with a maximum at 8 h postoperative to 1.15. The quality of RBA significantly correlated with the patient's pain during and at the end of surgery (P < 0.001). At the end of surgery (P < 0.001). At the end of surgery pain also correlated with the duration of surgery (P < 0.01). In 14 patients PCC was measured preoperatively. PCC decreased significantly after oral premedication with Lorazepam (18.4 to 12.6 micrograms/dl, P < 0.001). In the further course of surgery no significant differences in PCC could be detected in 26 patients. Pain during the operation correlated significantly with intraoperative (P = 0.01) and postoperative (P = 0.03) PCC. The objective stress parameters blood pressure and heart rate did not differ significantly during surgery. Of our patients, 77.4% decided that they would choose RBA again in case of ocular surgery.
Asunto(s)
Anestesia Local , Dimensión del Dolor , Dolor Postoperatorio/etiología , Vitrectomía , Vitreorretinopatía Proliferativa/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
S-Mephenytoin 4'-hydroxylase (CYP2C19) is a genetically polymorphic cytochrome P450. A modified method for CYP2C19 phenotyping was evaluated in 174 healthy German volunteers and the results were compared with genotyping for the intron4/exon5 G-->A splice site mutation (m1) of CYP2C19, associated with the poor metabolizer (PM) phenotype. A smaller than usual test-dose of 50 mg (R,S)-mephenytoin was used and urine samples were collected from 0 to 5 h and from 5 to 8 h after administration. Trait measurements included the mephenytoin S/R enantiomeric ratio and the hydroxylation index (i.e. the molar ratio of 4'-hydroxy-mephenytoin urinary recovery to the administered S-mephenytoin dose). S- and R-mephenytoin were quantified by isocratic HPLC with a Chiraspher column and 80% n-hexane and 20% dioxane as the mobile phase. All individuals from whom DNA was available (n = 140, including six phenotypically identified PMs) were analysed for the m1 mutation. The population frequency of this CYP2C19 mutation was 0.15. Four individuals were homozygous for m1 having S/R ratios of 0.9 or greater in both intervals of urine collection. Thus, individuals with an S/R ratio > or = 0.9 were classified as PMs and seven of all 174 phenotyped individuals were PMs (4%; 95% confidence limits: 1.6-8.1%). Heterozygous carriers of m1 (n = 34) had a median S/R ratio (5-8 h urine) of 0.06 compared to 0.01 in individuals without this mutation (n = 102; p = 0.0005, Mann-Whitney U-test). No such gene-dose relation was apparent with the hydroxylation index.(ABSTRACT TRUNCATED AT 250 WORDS)