Neutralizing monoclonal antibody could be an effective therapy fo

Neutralizing monoclonal antibody could be an effective therapy for the prevention of infection in a transplant setting. To pursue this treatment modality, we developed human monoclonal antibodies (HuMAbs) directed against the HCV E2 envelope glycoprotein and assessed the capacity of these HuMAbs to neutralize a broad panel of HCV genotypes. HuMAb antibodies were generated by immunizing transgenic mice containing human antibody genes (HuMAb mice; Medarex Inc.) with soluble E2 envelope glycoprotein derived from a genotype 1a virus (H77). Two HuMAbs, HCV1 and 95-2, selleck kinase inhibitor were selected for further study based on initial cross-reactivity with soluble E2 glycoproteins derived from genotypes 1a and 1b, as well as neutralization of lentivirus

pseudotyped with HCV 1a and 1b envelope glycoproteins. Additionally, HuMAbs HCV1 and 95-2 potently neutralized pseudoviruses from all genotypes tested (1a, 1b, 2b, 3a,

and 4a). Epitope mapping with mammalian and bacterially expressed proteins, as well as synthetic peptides, revealed that HuMAbs HCV1 and 95-2 recognize a highly conserved linear epitope spanning amino see more acids 412 to 423 of the E2 glycoprotein. The capacity to recognize and neutralize a broad range of genotypes, the highly conserved E2 epitope, and the fully human nature of the antibodies make HuMAbs HCV1 and 95-2 excellent candidates for treatment of HCV-positive individuals undergoing liver transplantation.”
“Retroviruses express Gag and Pol proteins by translation of unspliced genome-length viral RNA. For some retroviruses, transport of unspliced viral RNA to the cytoplasm is mediated by small regulatory proteins such as human immunodeficiency virus Rev, while other retroviruses contain constitutive transport elements CHIR98014 in vitro in their RNAs that allow transport without splicing. In this study, we found that the betaretrovirus Jaagsiekte sheep retrovirus (JSRV) encodes

within the env gene a trans-acting factor (Rej) necessary for the synthesis of Gag protein from unspliced viral RNA. Deletion of env sequences from a JSRV proviral expression plasmid (pTN3) abolished its ability to produce Gag polyprotein in transfected 293T cells, and Gag synthesis could be restored by cotransfection of an env expression plasmid (Delta GP). Deletion analysis localized the complementing activity ( Rej) to the putative Env signal peptide, and a signal peptide expression construct showed Rej activity. Two other betaretroviruses, mouse mammary tumor virus (MMTV) and human endogenous retrovirus type K, encode analogous factors ( Rem and Rec, respectively) that are encoded from doubly spliced env mRNAs. Reverse transcriptase-PCR cloning and sequencing identified alternate internal splicing events in the 5 ‘ end of JSRV env that could signify analogous doubly spliced Rej mRNAs, and cDNA clones expressing two of them also showed Rej activity. The predicted Rej proteins contain motifs similar to those found in MMTV Rem and other analogous retroviral regulatory proteins.

We conclude that replication under RNA-depleted conditions did no

We conclude that replication under RNA-depleted conditions did not modify RML prion strain properties. Our study cannot, however, exclude small variations of RML properties that would explain the abnormal clinical phenotype observed. We hypothesize that RNA molecules may act as catalysts of prion replication and that variable capacities of distinct

prion strains to utilize different cofactors may explain strain-specific dependency upon RNA.”
“Active middle ear implants (aMEI) are being increasingly used for hearing selleck kinase inhibitor restoration in congenital aural atresia. The existing gradings used for CT findings do not meet the requirements for these implants. Some items are expendable, whereas other important imaging factors are missing. We aimed to create a new grading system that could describe the extent of the malformation and predict the viability and challenges of implanting an aMEI.

One hundred three malformed ears were evaluated using HRCT of the temporal bone. The qualitative items middle ear and mastoid pneumatization,

oval window, stapes, round window, tegmen mastoideum displacement and facial nerve displacement were included. An anterior- and posterior round window corridor, oval window and stapes corridor were quantified and novelly included. They describe the size of the surgical field and the sight towards the windows.

The ears were graded on a 16-point scale (16-13 easy, 12-9 moderate, 8-5 difficult, 4-0 high risk). The strength of agreement between the calculated score and the performed implantations was good. The comparison of the new 16-point AZD1480 scale with the Jahrsdoerfer score showed that both were able to conclusively detect the high-risk group; however, the new 16-point scale was able to further determine which malformed ears were favorable for aMEI, which the Jahrsdoerfer score could not do.

The Active Middle

selleck Ear Implant Score for aural atresia (aMEI score) allows more precise risk stratification and decision making regarding the implantation. The use of operative corridors seems to have significantly better prognostic accuracy than the Jahrsdoerfer score.”
“Attempts to simultaneously control food intake and smoking may lead to smoking cessation failure. We sought to model this relationship using a human laboratory paradigm of smoking lapse behavior.

We examined the combined effect of food and nicotine deprivation, compared to nicotine deprivation alone, on the ability to resist smoking and on subsequent ad libitum smoking.

In a between-subjects design, daily smokers (N = 30) were all deprived of nicotine for 18 h and were either food-deprived (12 h) or not during a laboratory session. Following exposure to individualized food cues, participants had the option of initiating tobacco self-administration or delaying up to 50 min in exchange for monetary reinforcement.

This should provide a better and safer application and decrease t

This should provide a better and safer application and decrease the danger of premature rupture.

RESULTS: From January 2006 to July 2008, 55 aneurysms were clipped in 45 patients. The most common aneurysm location was the anterior communicating artery (20 patients) followed by the M1 segment of the middle cerebral artery (16 patients). Four

patients had 2, one had 3, and one Idasanutlin supplier had 5 aneurysms. Two clipping procedures were performed for an ateriovenous malformation-associated aneurysm. All aneurysms were clipped without any technical complication.

CONCLUSION: The use of the new clip system, especially in complex aneurysm surgery, has potential benefits because of the better surgical vision during clip application and the wider opening of the clip jaws. It is easy to handle and compatible with magnetic resonance imaging.”
“Exposure to traffic-related ambient air pollution, such as diesel exhaust

particles (DEP), is associated with adverse health outcomes, especially in individuals with preexisting find more inflammatory respiratory diseases. Using an analogous novel in vitro system to model both the healthy and inflamed lung, the susceptibility of epithelial cells exposed to DEP of varying organic carbon content was studied. Murine LA-4 alveolar type II-like epithelial cells, as well as primary murine tracheal epithelial cells (MTE), were treated with exogenous cytokines (tumor necrosis factor [TNF] + interleukin [IL]-1 + interferon [IFN] ) to model a mild inflammatory state. Epithelial cells were subsequently exposed to DEP of varying organic carbon content, and the resultant cytotoxic, cytoprotective, or antioxidant cell responses were inferred by changes in lactate dehydrogenase

(LDH) release, Prexasertib supplier heme oxygenase-1 (HO-1) expression, or glutathione levels, respectively. Data showed that exposure of healthy LA-4 cells to organic carbon-rich DEP (25 g/cm2; 24 h) induced adaptive cytoprotective/antioxidant responses with no apparent cell injury. In contrast, exposure of inflamed LA-4 cells resulted in oxidative stress culminating in significant cytotoxicity. Exposure of healthy MTE cells to organic carbon-rich DEP (20 g/cm2; 24 h) was seemingly without effect, whereas exposure of inflamed MTE cells resulted in increased epithelial solute permeability. Thus, surface lung epithelial cells stressed by a state of inflammation and then exposed to organic carbon-rich DEP appear unable to respond to the additional oxidative stress, resulting in epithelial barrier dysfunction and injury. Adverse health outcomes associated with exposure to traffic-related air pollutants, like DEP, in patients with preexisting inflammatory respiratory diseases may be due, in part, to similar mechanisms.”
“BACKGROUND: Despite its proven safety, intraoperative intratumoral hemorrhage is an uncommon but serious complication of stereotactic brain biopsy.

In contrast, Gairdner’s shrew-mice (Mus pahari) do express functi

In contrast, Gairdner’s shrew-mice (Mus pahari) do express functional XPR1. To determine whether Mus pahari could serve as a model for XMRV, primary Mus pahari fibroblasts and mice were infected with cell-free XMRV. Infection of cells in vitro resulted in XMRV Gag expression and the production of XMRV virions. After intraperitoneal injection of XMRV into Mus pahari mice, XMRV proviral DNA could be detected in spleen, blood, and brain. Intravenous administration of a green fluorescent protein (GFP) vector pseudotyped with XMRV produced GFP(+) CD4(+)

T cells and CD19(+) B cells. Mice mounted adaptive immune responses against XMRV, as evidenced by the production of neutralizing and Env- and Gag-specific 5-Fluoracil cost antibodies. Prominent G-to-A hypermutations were also found in viral genomes isolated from the spleen, suggesting intracellular restriction of XMRV infection by APOBEC3 in vivo. These data demonstrate infection of Mus pahari by XMRV, potential cell tropism of the virus, and immunological and intracellular selleck chemical restriction of virus infection in vivo. These data support the use of Mus pahari as a model for XMRV pathogenesis and as a platform for vaccine and drug development against this potential human pathogen.”
“The first influenza pandemic of the new millennium was caused by a newly emerged swine-origin influenza virus (SOIV) (H1N1). This new virus is characterized

by a previously unknown constellation of gene segments derived from North American and Eurasian swine lineages and the absence of common markers predictive of human adaptation. Overall, human infections appeared to be mild, but an alarming number of young Evofosfamide datasheet individuals presented with symptoms atypical for seasonal influenza. The new SOIV also showed a sustained

human-to-human transmissibility and higher reproduction ratio than common seasonal viruses, altogether indicating a higher pathogenic potential for this newly emerged virus. To study the virulence of the SOIV, we used a recently established cynomolgus macaque model and compared parameters of clinical disease, virology, host responses, and pathology/histopathology with a current seasonal H1N1 virus. We here show that infection of macaques with two genetically similar but clinically distinct SOIV isolates from the early stage of the pandemic (A/Mexico/4108/2009 and A/Mexico/InDRE4487/2009) resulted in upper and lower respiratory tract infections and clinical disease ranging from mild to severe pneumonia that was clearly advanced over the mild infection caused by A/Kawasaki/UTK-4/2009, a current seasonal strain. Unexpectedly, we observed heterogeneity among the two SOIV isolates in virus replication, host transcriptional and cytokine responses, and disease progression, demonstrating a higher pathogenic potential for A/Mexico/InDRE4487/2009.

(C) 2010 Published

(C) 2010 Published Akt inhibitor by Elsevier Inc.”
“Compelling evidence has documented the anxiolytic and mood-enhancing properties of cannabis. In susceptible users, however, consumption of this drug is conducive to panic, paranoia and dysphoria. We hypothesized that the up-regulation of CB1 receptors (CB(1)Rs) in select brain

regions may enhance the vulnerability to cannabinoid-induced anxiety. To test this possibility, we assessed the behavioral impact of a potent cannabinoid agonist (CP55,940; 0.05-0.1 mg/kg, IP) on C57BL/6 male mice, respectively subjected to a prolonged pre-treatment of either the selective CB1R antagonist/inverse agonist AM251 (1 mg/kg/day IP, for 21 days, followed by a 3-day clearance period before testing) or its vehicle (VEH1). Anxiety-like responses were studied in the novel open field, elevated plus maze (EPM) and social Selleck Pritelivir interaction assays. While CP55,940 induced

anxiolytic-like effects in the EPM in VEH1-exposed animals, it elicited opposite actions in AM251-exposed mice. In this last group, CP55,940 also reduced rearing and social interaction in comparison to its vehicle (VEH2). The divergent effects of CP55,940 in AM251- and VEH1-pretreated animals were confirmed in 129SvEv mice. Immunoblotting analyses on brain samples of C57BL/6 mice revealed that AM251 pre-treatment caused a significant up-regulation of CB1R expression in the prefrontal cortex and striatum, but also a down-regulation of these receptors in the hippocampus and midbrain. Notably, CB1R levels in the prefrontal cortex were negatively correlated with anxiolysis-related indices in the EPM; furthermore, midbrain CB1R expression was positively correlated with the total duration of social interaction. These results suggest that regional variations in brain CB1R expression

may differentially condition the behavioral effects of cannabinoids with respect to anxiety-related responses. (C) 2013 Elsevier Ltd. All rights reserved.”
“Background: Many patients with drug addiction are reported to have comorbid mood disorders. One of the suggested pathophysiological mechanisms for BTSA1 mood disorders is disruption of circadian rhythms. Several animal studies have shown that methamphetamine altered the expression of circadian clock molecules in the brain. Therefore, it is possible that mood disorders and drug addiction have common susceptibility genes.

Recently, we reported that the prokineticin 2 receptor gene (PROKR2) was associated with mood disorders including major depressive disorder and bipolar disorder in the Japanese population. In the present study, therefore, we conducted an association analysis of tagging SNPs in PROKR2 with Japanese methamphetamine dependence patients.

The ethanol fermentation co-product corn distillers dried grains

The ethanol fermentation co-product corn distillers dried grains with solubles could be useful commercially as a substrate for A. niger citric acid production.”
“Introduction We aimed to devise a rating method for key frontal and temporal brain regions validated against quantitative volumetric methods and applicable to a range of dementia syndromes.

Methods Four standardised coronal MR images from 36 subjects encompassing controls Z-DEVD-FMK and cases with

Alzheimer’s disease (AD) and frontotemporal dementia (FTD) were used. After initial pilot studies, 15 regions produced good intra-and inter-rater reliability. We then validated the ratings against manual volumetry and voxel-based morphometry (VBM) and compared ratings across the subject groups.

Results Validation against both manual volumetry (for both frontal and temporal lobes), and against whole brain VBM, showed good correlation with visual ratings for the majority of the brain regions. Comparison of rating scores across disease groups showed involvement of the anterior fusiform gyrus, anterior hippocampus and temporal pole in semantic dementia, while anterior cingulate and orbitofrontal

regions were involved in behavioural variant FTD.

Conclusion This simple visual rating can be used as an alternative to highly technical methods of quantification, and may be superior when dealing with single Dinaciclib cases or small groups.”
“To examine stool specimens from children with diarrhea from Parana State, southern Brazil, for presence of STEC.

A PCR screening assay for stx genes was used to examine a loopful of confluent colonies of 306 stool samples cultures. In six (1.96%) of them, DNA fragments of the expected size were observed, and the presence of stx was confirmed by DNA sequencing. Then up to 100 single colonies from each of the six stool cultures were analyzed using the same PCR protocol. However, stx-positive colonies were found only in two of the cultures. The E. coli strains belonged to serotypes O69:H11 and O178:H19, and presented genotypes stx(1)eae ehxA and stx(1) respectively. Shiga toxin production was confirmed using the VTEC Screen

Seiken. Except ampicillin, they were susceptible to all the antimicrobials tested.

These results show find more that STEC may be an important cause of diarrhea in children of Parana State, and that they are present in low numbers in stools. The strains belonged to serotypes not commonly found associated with STEC and probably present low virulence.

These results indicate that molecular methods are required to diagnosis of STEC infections.”
“Introduction Extracranial-intracranial (EC/IC) bypass is a useful procedure for the treatment of cerebral vascular insufficiency or complex aneurysms. We explored the role of multidetector computed tomography angiography (MDCTA), instead of digital subtraction angiography (DSA), for the postoperative assessment of EC/IC bypass patency.

Although TNPO3 was localized primarily to the cytoplasm, depletio

Although TNPO3 was localized primarily to the cytoplasm, depletion of TNPO3 from target cells inhibited HIV-1 infection without reducing the accumulation of nuclear proviral DNA, suggesting that TNPO3 facilitates a stage of the virus life cycle subsequent to nuclear entry. Our results suggest that TNPO3 and cyclophilin A facilitate

HIV-1 check details infection by coordinating proper uncoating of the core in target cells.”
“8-Nitroguanosine 3′,5′-cyclic monophosphate (8-nitro-cGMP) is a unique derivative of guanosine 3′,5′-cyclic monophosphate (cGMP) formed in mammalian and plant cells in response to production of nitric oxide and reactive oxygen species. 8-Nitro-cGMP possesses signaling activity inherited from parental cGMP, including induction of vasorelaxation through activation selleck chemicals of cGMP-dependent protein kinase. On the other hand, 8-nitro-cGMP mediates cellular signaling that is not observed for native cGMP, e.g., it behaves as an electrophile and reacts with protein sulfhydryls, which results in cGMP adduction to protein sulfhydryls (protein S-guanylation). Several proteins have been identified as targets for endogenous protein S-guanylation, including Kelch-like ECH-associated protein 1 (Keap1), H-Ras, and mitochondrial heat shock proteins. 8-Nitro-cGMP signaling via protein

S-guanylation of those proteins may have evolved to convey adaptive cellular stress responses. 8-Nitro-cGMP may not undergo conventional cGMP metabolism because of its resistance to phosphodiesterases. Hydrogen sulfide has recently been identified as a potent regulator for metabolisms of electrophiles

including 8-nitro-cGMP, through sulfhydration of electrophiles, e.g., leading to the formation of 8-SH-cGMP. Better understanding of the molecular basis for the formation, signaling functions, and metabolisms of 8-nitro-cGMP would be useful for the development GDC-0994 research buy of new diagnostic approaches and treatment of diseases related to oxidative stress and redox metabolisms. (C) 2013 Elsevier Inc. All rights reserved.”
“Stress and high levels of glucocorticoids during pre- and early postnatal life seem to alter developmental programs that assure dopaminergic transmission in the mesolimbic, mesocortical, and nigrostriatal systems. The induced changes are likely to be determined by the ontogenetic state of development of these brain regions at the time of stress exposure and their stability is associated with increased lifetime susceptibility to psychiatric disorders, including drug addiction. This article is intended to serve as a starting point for future studies aimed at the attenuation or reversal of the effects of adverse early life events on dopamine-regulated behaviors.”
“CD8(+) T cells inhibit virus replication in SIV-infected rhesus macaques.

0081 and 0 0169, respectively)

Conclusions: While a m

0081 and 0.0169, respectively).

Conclusions: While a microfocus of Gleason score 6 prostate cancer on biopsy is commonly considered low risk disease, there was a greater than 1/5 risk of pathological upgrading and/or up staging. Patients with Gleason score 6 microfocal prostate cancer should be counseled that they may harbor more aggressive disease, especially when pretreatment clinical risk factors are present, such as advanced age or high clinical prostate specific antigen density.”
“A bidirectional association between mood disorders and cardiovascular diseases has been described in humans, yet the precise neurobiological www.selleckchem.com/products/Erlotinib-Hydrochloride.html mechanisms that underlie

this association are not fully understood. This article is focused on neurobiological processes and mediators in mood and cardiovascular disorders, with an emphasis on common mechanisms including stressor reactivity, neuroendocrine and neurohumoral changes, immune alterations, autonomic and cardiovascular dysregulation, and central neurotransmitter and neuropeptide dysfunction. A discussion of the utility of experimental investigations with rodent models, including those in rats and prairie votes (Microtus ochrogaster), is presented. Specific studies using these models are reviewed, focusing on the analysis

of behavioral, physiological and neural mechanisms underlying depressive disorders and cardiovascular disease. Considered in combination with studies using human samples, the investigation of mechanisms underlying depressive behaviors and cardiovascular regulation using animal CH5183284 in vitro models will enhance our understanding of the association of depression and cardiovascular disease, and will promote the development of improved interventions for individuals with these detrimental disorders. (C) 2008 Elsevier Ltd. All rights reserved.”
“Purpose: Recent data have shown that high grade prostate cancer is a potentially 4-Hydroxytamoxifen research buy surgically curable disease in properly selected patients. We assessed the ability of preoperative variables to predict extraprostatic extension in men with biopsy Gleason score 8 or greater.

Materials and Methods:

We identified 159 patients who underwent prostatectomy without neoadjuvant therapy for biopsy proven Gleason score 8 or greater T1c-T2N0M0 cancer between 1996 and 2006. Univariate and multivariate analyses were performed to predict extraprostatic extension using side specific data, including clinical features and biopsy findings.

Results: Organ confined cancer was pathologically confirmed in 84 of 159 patients (52.8%). Side specific analysis was practicable on 124 sides (124 men) and side specific extraprostatic extension was found on 48 of the 124 sides (38.7%). Gleason grade 5 element, maximum tumor length, percent of positive cores, positive basal cores and side specific palpable disease were significantly associated with side specific extraprostatic extension.

As a rest tissue that contains potent hematopoietic stem cells

As a rest tissue that contains potent hematopoietic stem cells

(HSCs), the human placenta could represent (in addition to umbilical cord blood cells) an accessible supplemental source of cells for therapeutic strategies.”
“Insight has emerged as a significant treatment outcome predictor in adult obsessive-compulsive disorder (OCD), with some suggesting that OCD with poor insight represents a distinct clinical subtype. Despite its clinical relevance, limited data exist on insight in pediatric OCD patients. The present study investigated the relation between poor insight and clinical characteristics among children and adolescents with OCD (N=78, ages 6-20 years). Forty-five percent of the Torin 1 purchase sample (n=35) was considered to have low levels MM-102 supplier of insight into their symptoms, as determined by clinician rating on item 11 of the Children’s Yale-Brown Obsessive-Compulsive Scale. Pearson product-moment correlations showed a significant, inverse relation between insight and OCD severity. Relative to the high insight group, parents of patients with low insight reported higher levels of OCD-related impairment and family accommodation. These findings suggest that

OCD with poor insight may represent a distinct clinical feature that may require more intensive and multimodal treatment approaches. (C) 2007 Elsevier Ireland Ltd. All rights reserved.”
“Aims: The objectives of this research were to (i) optimize the concentration of cycloheximide for use in WL media used in the wine industry and (ii) evaluate Dekkera/Brettanomyces differential medium (DBDM) as a means to detect Dekkera.

Methods and Results: Dekkera bruxellensis

and other yeasts were transferred into WL broths containing 0, 10, 50 or 100 mg l(-1) of cycloheximide. While several grew in 10 mg l(-1), only Hanseniaspora uvarum, Pichia guillermondii, Schizosaccharomyces pombe and D. bruxellensis tolerated >= E7080 50 mg l(-1) of the antibiotic. On solidified WL media after 8- days incubation, colony sizes of two strains of D. bruxellensis (B1b and ATCC 52905) decreased with increased concentrations of cycloheximide, while others (F3 and P2) were unaffected. Although D. bruxellensis B1b did not grow well on another selective medium, DBDM, colony development was improved by the addition of sterilized red wine.

Conclusions: Of the concentrations tested, 50 mg l(-1) cycloheximide inhibited many grape/wine yeasts yet generally yielded countable colonies of Dekkera (1-2.5 mm diameter). Several strains of Dekkera did not grow well on DBDM, probably due to the lack of an unidentified nutrient(s).

Significance and Impact of the Study: Better media formulations will improve the detection of Dekkera, thereby increasing microbiological control during winemaking.”
“Glomerulonephritides represent a diverse array of diseases that have in common immune cell-mediated effector mechanisms that cause organ damage.

Motor functions determined by beam crossing and gait analysis sho

Motor functions determined by beam crossing and gait analysis showed that CRF-OE mice took longer time and more steps to traverse a beam with more errors, and displayed reduced stride length compared to their WT littermates. These data show that CRF-OE mice display brain size reduction associated with alterations MK-8931 mouse of motor coordination and an increase in visceral fat mass providing a novel animal model to study mechanisms involved in brain atrophy under conditions of sustained elevation of brain CRF and circulating glucocorticoid levels. (C) 2010 Elsevier Ireland Ltd. All rights reserved.”
“Although many drugs inhibit the replication of Epstein-Barr virus

(EBV) in cell culture systems, there is still no drug that is effective and approved for use in primary EBV infection. More recently, maribavir (MBV), an L-ribofuranoside benzimidazole, has been shown to be a potent and nontoxic inhibitor of EBV replication and to have a mode of action quite distinct PF-02341066 price from that of acyclic nucleoside analogs such as acyclovir (ACV) that is based primarily on MBV’s ability to block the phosphorylation of target proteins by EBV and human cytomegalovirus

protein kinases. However, since the antiviral mechanisms of the drug are complex, we have carried out a comprehensive analysis of the effects of MBV on the RNA expression levels of all EBV genes with a quantitative real-time reverse transcription-PCR-based array. We show that in comparisons with ACV, the RNA expression profiles produced by the two drugs are entirely different, with MBV causing a pronounced inhibition of multiple viral mRNAs and with ACV causing virtually none. The results emphasize the different modes of action of the two drugs and suggest that the action of MBV may be linked to indirect effects on the transcription of EBV genes

through the interaction of BGLF4 with multiple viral proteins.”
“The pre-Botzinger complex (pre-BotC), a subregion of the ventrolateral medulla involved in respiratory Metabolism inhibitor rhythm generation, contains intrinsically bursting pacemaker neurons. A previous study proposed Hodgkin-Huxley type minimal models for pacemaker neurons and predicted the effect of a hyperpolarizing input on the dynamics of a model under certain conditions. In this model, bursting is explained by the dynamics of a persistent sodium current. In the present study, the effect of a hyperpolarizing input on the dynamics of a model was investigated under variable conditions. It was observed that immediately after an input of sufficient intensity and duration, an increase in the maximal value of the gating variable h of a persistent sodium current was brought about by a decrease in the timing of the hyperpolarizing input.