Restoring Light Sensitivity in Blind Retinae Using a Photochromic AMPA Receptor Agonist.

Retinal degenerative diseases can have many possible causes and are currently difficult to treat. As an alternative to therapies that require genetic manipulation or the implantation of electronic devices, photopharmacology has emerged as a viable approach to restore visual responses. Here, we present a new photopharmacological strategy that relies on a photoswitchable excitatory amino acid, ATA. This freely diffusible molecule selectively activates AMPA receptors in a light-dependent fashion. It primarily acts on amacrine and retinal ganglion cells, although a minor effect on bipolar cells has been observed. As such, it complements previous pharmacological approaches based on photochromic channel blockers and increases the potential of photopharmacology in vision restoration.

DNA methylation and differential gene regulation in photoreceptor cell death.

Retinitis pigmentosa (RP) defines a group of inherited degenerative retinal diseases causing progressive loss of photoreceptors. To this day, RP is still untreatable and rational treatment development will require a thorough understanding of the underlying cell death mechanisms. Methylation of the DNA base cytosine by DNA methyltransferases (DNMTs) is an important epigenetic factor regulating gene expression, cell differentiation, cell death, and survival. Previous studies suggested an involvement of epigenetic mechanisms in RP, and in this study, increased cytosine methylation was detected in dying photoreceptors in the rd1, rd2, P23H, and S334ter rodent models for RP. Ultrastructural analysis of photoreceptor nuclear morphology in the rd1 mouse model for RP revealed a severely altered chromatin structure during retinal degeneration that coincided with an increased expression of the DNMT isozyme DNMT3a. To identify disease-specific differentially methylated DNA regions (DMRs) on a genomic level, we immunoprecipitated methylated DNA fragments and subsequently analyzed them with a targeted microarray. Genome-wide comparison of DMRs between rd1 and wild-type retina revealed hypermethylation of genes involved in cell death and survival as well as cell morphology and nervous system development. When correlating DMRs with gene expression data, we found that hypermethylation occurred alongside transcriptional repression. Consistently, motif analysis showed that binding sites of several important transcription factors for retinal physiology were hypermethylated in the mutant model, which also correlated with transcriptional silencing of their respective target genes. Finally, inhibition of DNMTs in rd1 organotypic retinal explants using decitabine resulted in a substantial reduction of photoreceptor cell death, suggesting inhibition of DNA methylation as a potential novel treatment in RP.

[Computed tomography in cats with craniofacial trauma with regard to maxillary and orbital fractures]. / Computertomographische Untersuchung des Schädels von Katzen mit kraniofazialem Trauma im Hinblick auf Maxilla- und Orbitafrakturen.

OBJECTIVE: Computed tomographic examination of the skull of cats with craniofacial trauma. Analysis of diagnostic findings with regard to the occurrence of isolated and combined maxillary and orbital fractures. MATERIAL AND METHODS: Prospective study (August 2006 - June 2010): Computed tomography (CT) of the skull of cats with craniofacial trauma. RESULTS: Thirty-eight cats met the inclusion criteria. Breeds were 36 Domestic Shorthair cats, one Maine Coon and one Somali cat. Age at admission ranged from 11 to 187 months. The ratio of the numbers of males to females was 22:16 (1.4). Computed tomographic examination revealed a maxillary fracture in 27 (71%) animals. Sixteen (42%) cats had multiple maxillary fractures (≥2). Twenty-eight animals (74%) displayed orbital fractures. Combined maxillary and orbital fractures occurred in 26 (68%) patients. The odds ratio of this combined occurrence was 87 (p<0.001). Sixteen (57%) of 28 cats with orbital fractures showed multiple orbital fractures (≥2). The incidence of bilateral orbital fractures was 67% (25 patients). The medial orbital wall was the most commonly fractured orbital wall (66%), and the orbital floor the second most common (61%). CONCLUSION: Computed tomographic examination of the skull of cats with craniofacial trauma showed that maxillary and orbital fractures are more common than previously described. Combined maxillary and orbital fractures occurred in more than half of the patients. In cats, orbital fractures mainly affect the medial orbital wall and the orbital floor. CLINICAL RELEVANCE: Cats with craniofacial trauma often have maxillary and orbital fractures. The additional information taken from the computed tomographic examination could lead to an optimised therapeutical concept.

Neoplasias del intestino delgado / Small intestinal neoplasms

Small intestine tumors are infrequent lesions during the routine clinical practice. They appear sporadically, in association with genetic diseases (e.g familiar adenomatous polyposis or Peutz-Jeghers syndrome), or associated to chronic inflammatory diseases (e.g Crohn’s disease or celiac disease). Benign tumors of small intestine (e.g leiomyomas, lipomas, adenomas, hamartomas or desmoid tumors) are generally asymptomatic, and may show up with intussusception. Primary malignant small intestine tumors (e.g adenocarcinoma, leiomyosarcoma, carcinoid tumor and lymphoma), can appear with intestinal obstruction, jaundice, digestive bleeding or abdominal pain. Small intestine metastatic lesions can appear by nearness, peritoneal metastasis or by hematological way. This last dissemination type is infrequent and more typically of melanoma. Because of its low prevalence, unspecific symptomatology and relative inaccessibility by conventional endoscopy, the diagnostic of small intestine neoplasm is often made several months after the first symptoms. Enteroclysis is a useful imaging technique towards the small intestine neoplasm suspicion. The endoscopic capsule and enteroscopy are actually the best diagnostic and therapeutic methods for this type of neoplasm. The treatment depends in the type of neoplasm, being the tumoral resection the first-line therapy.

Los tumores de intestino delgado son lesiones infrecuentes en la práctica clínica habitual. Aparecen de forma esporádica en asociación con enfermedades genéticas (por ej., poliposis adenomatosa familiar o síndrome de Peutz-Jeghers), o bien asociados a enfermedades inflamatoria crónicas intestinales (por ej., enfermedad de Crohn o enfermedad celíaca). Los tumores benignos de intestino delgado (por ej., leiomiomas, lipomas, adenoma, hamartoma o tumor desmoide) son generalmente asintomáticos, pudiendomanifestarse con intususcepción. Los tumores malignos primarios de intestino delgado (por ej.,adenocarcinoma, leiomiosarcoma, carcinoide y linfoma), pueden presentarse con obstrucción intestinal, ictericia, sangramiento digestivo o dolor abdominal. Las lesiones metastásicas de intestino delgado pueden aparecer por contigüidad, metástasis peritoneal o por vía hematógena. Este último tipo de diseminación es infrecuente y más típico del melanoma. Debido a su baja prevalencia, sintomatología inespecífica y relativa inaccesibilidad por endoscopía convencional, el diagnóstico de las neoplasias de intestino delgado es realizado a menudo varios meses después de iniciado los síntomas. La enteroclisis es una técnica de imagen útil frente a la sospecha de neoplasia de intestino delgado. La cápsula endoscópica y la enteroscopía son los métodos actualmente de mayor rendimiento para el diagnóstico y eventual terapia de este tipo de neoplasias. El tratamiento depende del tipo de neoplasia, siendo la resección tumoral la terapia de primera línea.

[Enterocutaneous fistula formation in a dog as a result of colonic foreign body perforation]. / Enterokutane Fistelbildung infolge Perforation des Kolons durch einen hölzernen Fremdkörper bei einem Hund.

A 5-year-old female Poodle was presented with a 3-month history of recurrent abscess and fistula formation on the right abdominal wall. Radiographic and ultrasonographic examinations demonstrated an enterocutaneous fistula formation secondary to foreign body perforation of the colon. Additionally, the diagnosis of a pyometra was made. Twenty-four hours after surgical therapy (ventral midline coeliotomy, foreign body removal, closure of the colon perforation, abdominal lavage and drainage, revision of the fistula) the patient was euthanized due to sepsis and incipient multiorgan dysfunction.

Closed reduction and percutaneous fixation of sacroiliac luxations in cats using 2.4 mm cannulated screws - a cadaveric study.

OBJECTIVES: To describe fluoroscopically assisted percutaneous placement of 2.4 mm cannulated screws for fixation of artificially induced sacroiliac luxations in cats, and to evaluate the success of this technique in restoration of normal pelvic anatomy. METHODS: Fluoroscopically assisted closed reduction and percutaneous fixation of sacro-iliac luxations using 2.4 mm cannulated screws was performed in cadavers of 12 cats. Pre- and postoperative radiographs and postoperative computed tomographic scans were used to evaluate screw placement, screw purchase within the sacral body, reduction of the sacroiliac joint, pelvic canal diameter ratio, and hemipelvic canal width ratio. RESULTS: Mean total surgical time was 6 minutes and 10 seconds ± 53 seconds and mean total time of fluoroscopic screening for each procedure was 44 seconds ± 6 seconds. Mean percent of reduction was 98.33% and mean screw purchase within the sacral body was 73%. Eleven out of 12 screws were placed in a satisfactory location in the sacral body. Pelvic canal diameter ratio and hemipelvic canal width ratio indicated successful restoration of the pelvic anatomy. CLINICAL SIGNIFICANCE: Our results confirm that fluoroscopically assisted percutaneous placement of 2.4 mm cannulated screws is a feasible technique for fixation of sacroiliac luxations in cats. Mechanical properties of this fixation technique need to be evaluated before the use in clinical patients.

Disfunción del esfínter de Oddi y pancreatitis idiopática / Sphincter of Oddi dysfunction (SOD) and idiopatic pancreatitis

The sphincter of Oddi dysfunction is a little known entity that typically occurs in post-cholecystectomy patients with abdominal pain with biliary or pancreatic characteristics. It represents an important cause of idiopathic recurrent acute pancreatitis. Most of the patients referred for sphincter of Oddi dysfunction study have another disease which explain the symptoms, so a careful history and appropriate physical examination often can identify the true source of the pain. The most used grading score is the Milwaukee classification, based on clinical, laboratory, imaging and cholangiographic findings. In the last decade, new and more applicable criteria have been developed, such as Rome III criteria, which do not require functional tests considered complex and not available in non-specialized centers. The sphincter of Oddimanometry is considered the gold standard for the diagnosis of this entity, allowing for the determination of which patients will benefit from endoscopic therapy (sphincterotomy). There are some noninvasive diagnostic tests that have failed to show strong correlation to displace the sphincter of Oddi. The treatment of this condition is mainly based on endoscopic sphincterotomy, with variable success rates depending on the type of dysfunction. This article presents a review of the most important aspects related to the sphincter of Oddi and its relationship with idiopathic recurrent pancreatitis.

La disfunción del esfínter de Oddi es una entidad poco conocida, que típicamente se presenta en pacientes post-colecistectomía con dolor abdominal de tipo “biliar” o “pancreático”. Representa unaimportante causa de pancreatitis aguda recurrente idiopática. La mayoría de los pacientes derivados para estudio de disfunción del esfínter de Oddi corresponden a otra causa o enfermedad que explica los síntomas, por lo que una cuidadosa historia clínica y un adecuado examen físico, a menudo permiten identificar el verdadero origen del cuadro doloroso. La clasificación más utilizada es la de Milwaukee basada en parámetros clínicos, de laboratorio, imagenológicos y colangiográficos. En la última década, se han elaborado criterios de mayor aplicabilidad clínica como los criterios de Roma III, que no requieren de test funcionales considerados complejos y poco disponibles en centros no especializados. La manometría del esfínter de Oddi es considerado el gold standard en el diagnóstico de esta entidad, permitiendo además, establecer quiénes se beneficiarán con la terapia endoscópica (esfinterotomía). Se han desarrollado una serie de otros métodos diagnósticos no invasivos, que no han logrado demostrar una correlación suficientemente sólida para desplazar a la manometría. El tratamiento de esta condición se basa principalmente en la esfinterotomía endoscópica, con una tasa de éxito variable dependiendo del tipo de disfunción. En el presente artículo se revisarán los aspectos más importantes relacionados con la disfunción del esfínter de Oddi y su relación con pancreatitis recurrente idiopática.

Altered synaptic plasticity and behavioral abnormalities in CNGA3-deficient mice.

The role of the cyclic nucleotide-gated (CNG) channel CNGA3 is well established in cone photoreceptors and guanylyl cyclase-D-expressing olfactory neurons. To assess a potential function of CNGA3 in the mouse amygdala and hippocampus, we examined synaptic plasticity and performed a comparative analysis of spatial learning, fear conditioning and step-down avoidance in wild-type mice and CNGA3 null mutants (CNGA3(-/-) ). CNGA3(-/-) mice showed normal basal synaptic transmission in the amygdala and the hippocampus. However, cornu Ammonis (CA1) hippocampal long-term potentiation (LTP) induced by a strong tetanus was significantly enhanced in CNGA3(-/-) mice as compared with their wild-type littermates. Unlike in the hippocampus, LTP was not significantly altered in the amygdala of CNGA3(-/-) mice. Enhanced hippocampal LTP did not coincide with changes in hippocampus-dependent learning, as both wild-type and mutant mice showed a similar performance in water maze tasks and contextual fear conditioning, except for a trend toward higher step-down latencies in a passive avoidance task. In contrast, CNGA3(-/-) mice showed markedly reduced freezing to the conditioned tone in the amygdala-dependent cued fear conditioning task. In conclusion, our study adds a new entry on the list of physiological functions of the CNGA3 channel. Despite the dissociation between physiological and behavioral parameters, our data describe a so far unrecognized role of CNGA3 in modulation of hippocampal plasticity and amygdala-dependent fear memory.

Diarrea por clostridium difficile / Clostridium difficile-associated diarrhea

Clostridium difficile (CD), es un bacilo gram positivo, anaerobio formador de esporas identificado como la principal causa de diarrea asociado al uso de antibióticos en pacientes hospitalizados. Los dos factores de riesgo más importantes para adquirir esta infección son el uso reciente de terapia antimicrobiana y la exposición al microorganismo productor de toxinas. La epidemiología de la enfermedad asociada a Clostridium difficile (EACD) ha cambiado sustancialmente en la última década, con un incremento sostenido en la incidencia y aparición de casos más severos, refractarios y recurrentes. La EACD abarca un amplio espectro de manifestaciones clínicas, que van de la portación asintomática, pasando por un cuadro de diarrea leve, hasta el desarrollo de colitis fulminante con una elevada tasa de mortalidad. El tratamiento antibiótico estándar es el metronidazol y vancomicina oral, con tasas de respuesta cercanas a un 95 por ciento por ; sin embargo, luego de la aparición de cepas “hipervirulentas” en el año 2003, la tasa de respuesta al metronidazol ha disminuido en forma significativa. Por ello, en los últimos años, se han comunicado una serie de estrategias y estudios con nuevos antimicrobianos con resultados alentadores. La terapia inmunológica pareciera tener un rol importante en la prevención de recurrencias así como en el manejo de pacientes con enfermedad severa. Se revisan aquellos aspectos más importantes relacionados con la infección asociada a CD.

Clostridium difficile (CD) is an anaerobic, gram-positive, spore-forming, toxin-producing bacillus. This is the leading cause of nosocomial diarrhea associated with antibiotic therapy in hospitalized patients. The two major risk factors for C. Difficile associated disease (CDAD) are recent exposure to an antibiotic and exposure to a toxin producing strain of the microorganism. Epidemiology of CDAD has changed substantially in the last decade, with an increase of incidence and occurrence of more severe, refractory and recurrent episodes. CDAD clinical spectrum varies from asymptomatic carriers, going from mild diarrhea to fulminant colitis with a high mortality rate. The standard antibiotic treatment is oral metronidazole and vancomycin, with response rates close to 90 percent, but after the appearance of “hypervirulent” strains in 2003, the response rate has decreased significantly. Therefore, in recent years many trials have reported a series of strategies and studies with new antimicrobial agents with promising results. Immunotherapy appears to play an important role in preventing recurrence and in the management of patients with a severe disease. The present article will review the most important aspects related to the infection associated with CD.

Induction of STAT3-related genes in fast degenerating cone photoreceptors of cpfl1 mice.

Cone dystrophies are genetic diseases characterized by loss of cone photoreceptor function and severe impairment of daylight vision. Loss of function is accompanied by a progressive degeneration of cones limiting potential therapeutic interventions. In this study we combined microarray-based gene-expression analysis with electroretinography and immunohistochemistry to characterize the pathological processes in the cone photoreceptor function loss 1 (cpfl1) mouse model. The cpfl1-mouse is a naturally arising mouse mutant with a loss-of-function mutation in the cone-specific Pde6c gene. Cpfl1-mice displayed normal rod-specific light responses while cone-specific responses were strongly diminished. Despite the lack of a general retinal degeneration, the cone-specific functional defect resulted in a marked activation of GFAP, a hallmark of Müller-cell gliosis. Microarray-based network-analysis confirmed activation of Müller-glia-specific transcripts. Unexpectedly, we found up-regulation of the cytokine LIF and the anti-apoptotic transcription factor STAT3 in cpfl1 cone photoreceptors. We postulate that STAT3-related pathways are induced in cpfl1 cone photoreceptors to counteract degeneration.

HCN channels: structure, cellular regulation and physiological function.

Hyperpolarization-activated and cyclic nucleotide-gated (HCN) channels belong to the superfamily of voltage-gated pore loop channels. HCN channels are unique among vertebrate voltage-gated ion channels, in that they have a reverse voltage-dependence that leads to activation upon hyperpolarization. In addition, voltage-dependent opening of these channels is directly regulated by the binding of cAMP. HCN channels are encoded by four genes (HCN1-4) and are widely expressed throughout the heart and the central nervous system. The current flowing through HCN channels, designated I(h) or I(f), plays a key role in the control of cardiac and neuronal rhythmicity ("pacemaker current"). In addition, I(h) contributes to several other neuronal processes, including determination of resting membrane potential, dendritic integration and synaptic transmission. In this review we give an overview on structure, function and regulation of HCN channels. Particular emphasis will be laid on the complex roles of these channels for neuronal function and cardiac rhythmicity.

Interaction of the photobactericides methylene blue and toluidine blue with a fluorophore in Pseudomonas aeruginosa cells.

BACKGROUND AND OBJECTIVES: The difference in photobactericidal efficacy between methylene blue (MB) and toluidine blue (TB) may be explained by their involvement with proteins, lipopolysaccharides (LPS), and siderophores and siderophore-receptor protein complexes on the bacterial outer membrane. This study aims to determine if this is the case by using the fluorescence given off by a pseudomonal siderophore named pyoverdin. STUDY DESIGN/MATERIALS AND METHODS: Confocal laser scanning microscopy was used to observe the fluorescence of Pseudomonas aeruginosa cells excited at 488 nm in the presence of increasing dye concentrations. RESULTS: Cellular fluorescence at 522 nm progressively decreased with increasing dye concentrations. The Stern-Volmer constants for cellular fluorescence quenching with the dyes were compared to the association constants for dyes complexed with LPS. The quenching of cellular fluorescence was associated with the formation of a ground-state complex between the dyes and pyoverdin-FpvA protein system. MB readily complexed with this system, whereas TB complexed more strongly with LPS. CONCLUSION: The different affinities of the dyes for both pyoverdin-protein and LPS will affect the contributions of the dyes' interactions with these biopolymers to the overall bacterial photodamage.

Reliability of personality disorder diagnosis during depression: the contribution of collateral informant reports.

OBJECTIVE: Research has found low concordance of personality disorder diagnoses made during depression versus after remission and made using patient versus collateral informants, but little is known about the reliability of personality disorder (PD) diagnoses made during depression using patient and collateral reports. METHOD: A total of 168 patients were evaluated for PDs during depression and following response using patient and close informant reports. kappa coefficients of inter-informant and test-retest reliability were calculated. RESULTS: After depression response, the proportion diagnosed with cluster A and C PDs fell by both patient and close informant report, and overall inter-informant reliability declined. Overall test-retest reliability did not differ between patients and informants. CONCLUSION: Collateral informants do not improve the reliability of PD diagnoses made during depressive episodes.

Advances in photodynamic therapy for the treatment of head and neck cancers.

Photodynamic therapy (PDT) is an FDA-approved minimally invasive medical treatment modality that utilizes light in the presence of oxygen to activate photosensitizing agents that are relatively selectively concentrated in abnormal or neoplastic cells resulting in cell death. At the present time, PDT has been approved for clinical treatment in the United States, European Union, Canada, Russia, and Japan. In the United States, US Food and Drug administration approval has been given for the use of PDT in the treatment of Barrett's esophagus, obstructing esophageal carcinoma and early and obstructing tracheobronchial carcinoma using the photosensitizer Photofrin; actinic keratosis using the photosensitizer Levulan (aminolevulinic acid); and macular degeneration using the photosensitizer BPD. In the EU the above noted indications have also been approved in addition to the treatment of early head and neck cancers and palliative treatment of head and neck cancer using the photosensitizer Foscan; and treatment of basal and squamous cell skin cancers using the photosensitizer Metvix.

[Noninvasive diagnosis of posttraumatic thoracic splenosis]. / Diagnóstico no invasivo de la esplenosis torácica postraumática.

Thoracic splenosis is a rare occurrence that has usually been diagnosed by invasive procedures to allow a pathologic diagnosis to be reached. A firm diagnosis can now be made with the help of new, noninvasive imaging techniques. We report the case of a 34-year-old man with a history of severe thoracic-abdominal injury, including rupture of the spleen and left diaphragm. During computed tomography of the thorax related to a different diagnosis, nonspecific nodules were observed, although the patient was asymptomatic. A suspected diagnosis of thoracic splenosis was confirmed by technetium-99 sulfur colloid scintigraphy.

Melanopsin and rod-cone photoreceptive systems account for all major accessory visual functions in mice.

In the mammalian retina, besides the conventional rod-cone system, a melanopsin-associated photoreceptive system exists that conveys photic information for accessory visual functions such as pupillary light reflex and circadian photo-entrainment. On ablation of the melanopsin gene, retinal ganglion cells that normally express melanopsin are no longer intrinsically photosensitive. Furthermore, pupil reflex, light-induced phase delays of the circadian clock and period lengthening of the circadian rhythm in constant light are all partially impaired. Here, we investigated whether additional photoreceptive systems participate in these responses. Using mice lacking rods and cones, we measured the action spectrum for phase-shifting the circadian rhythm of locomotor behaviour. This spectrum matches that for the pupillary light reflex in mice of the same genotype, and that for the intrinsic photosensitivity of the melanopsin-expressing retinal ganglion cells. We have also generated mice lacking melanopsin coupled with disabled rod and cone phototransduction mechanisms. These animals have an intact retina but fail to show any significant pupil reflex, to entrain to light/dark cycles, and to show any masking response to light. Thus, the rod-cone and melanopsin systems together seem to provide all of the photic input for these accessory visual functions.

Treatment of oral candidiasis with methylene blue-mediated photodynamic therapy in an immunodeficient murine model.

OBJECTIVES: The purpose of this study was to evaluate the efficacy of using methylene blue (MB)-mediated photodynamic therapy to treat oral candidiasis in an immunosuppressed murine model, mimicking what is found in human patients. STUDY DESIGN: Seventy-five experimental mice with severe combined immunodeficiency disease were inoculated orally with Candida albicans by swab 3 times a week for a 4-week period. On treatment day, mice were cultured for baseline fungal growth and received a topical oral cavity administration of 0.05 mL MB solution at one of the following concentrations: 250, 275, 300, 350, 400, 450, or 500 microgram/mL. After 10 minutes the mice were recultured and underwent light activation with 664 nm of diode laser light with a cylindrical diffuser. After photodynamic therapy the mice were cultured again for colony-forming units per milliliter and then killed, their tissue harvested for histopathology. RESULTS AND CONCLUSIONS: The results indicate an MB dose-dependent effect. Concentrations from 250 to 400 microgram/mL reduced fungal growth but did not eliminate Candida albicans. MB concentrations of 450 and 500 microgram/mL totally eradicated Candida albicans from the oral cavity, resulting in reductions from 2.5 log(10) and 2.74 log(10) to 0, respectively. These results suggest that MB-mediated photodynamic therapy can potentially be used to treat oral candidiasis in immunodeficient patients.

Differential and age-dependent expression of hyperpolarization-activated, cyclic nucleotide-gated cation channel isoforms 1-4 suggests evolving roles in the developing rat hippocampus.

Hyperpolarization-activated cation currents (I(h)) are found in several brain regions including thalamus and hippocampus. Important functions of these currents in promoting synchronized network activity and in determining neuronal membrane properties have been progressively recognized, but the molecular underpinnings of these currents are only emerging. I(h) currents are generated by hyperpolarization-activated, cyclic nucleotide-gated cation channels (HCNs). These channel proteins are encoded by at least four HCN genes, that govern the kinetic and functional properties of the resulting channels. Because of the potential impact of I(h)-mediated coordinated neuronal activity on the maturation of the functional hippocampal network, this study focused on determining the expression of the four members of the HCN gene family throughout postnatal hippocampal development at both the regional and single cell level.The results of these experiments demonstrated that HCNs 1, 2 and 4 are differentially expressed in interneuronal and principal cell populations of the rat hippocampal formation. Expression profiles of each HCN isoform evolve during postnatal development, and patterns observed during early postnatal ages differ significantly from those in mature hippocampus. The onset of HCN expression in interneurons of the hippocampus proper precedes that in the dentate gyrus, suggesting that HCN-mediated pacing activity may be generated in hippocampal interneurons prior to those in the hilus. Taken together, these findings indicate an age-dependent spatiotemporal evolution of specific HCN expression in distinct hippocampal cell populations, and suggest that these channels serve differing and evolving functions in the maturation of coordinated hippocampal activity.

Comparison of the methylene blue and toluidine blue photobactericidal efficacy against gram-positive and gram-negative microorganisms.

BACKGROUND AND OBJECTIVE: Studies on the photobactericidal efficacy of methylene blue (MB) and toluidine blue (TB) have shown inconsistent results in the literature. This study evaluated the bactericidal efficacy of MB and TB against different bacteria under light and dark conditions to determine the most effective bactericidal dye. STUDY DESIGN/MATERIALS AND METHODS: Suspensions of Staphylococcus aureus, Streptococcus pneumoniae, Enterococcus faecalis, Hemophilus influenzae, Escherichia coli, and Pseudomonas aeruginosa in saline were treated in dark and red laser light conditions in the presence of each dye using an argon pumped-dye and a diode laser emitting light at 630 and 664 nm, respectively. The effect of dye concentration, dark incubation time, the fluence and intensity of laser light on the destruction of different bacteria were compared. RESULTS: Both dyes eradicated all examined bacteria under laser light. The complete photodestruction of microorganisms was reached at TB concentrations of 1.5-7-fold less than that of MB. CONCLUSION: TB exhibits a greater bactericidal activity than MB against most bacteria in dark and light conditions. Mostly, these results are consistent with their respective dye partition coefficients.