Miracle-dz/UniFAR-FTUs huggingface dataset:
Behavioral effects of neuropeptide Y receptor agonists in the elevated plus‐maze and fear‐potentiated startle procedures

Evidence from animal studies has led to the proposal that neuropeptide Y (NPY) has anxiolytic-like effects in rats after intracerebroventricular (i.c.v.) administration. The purpose of the present study was to extend these observations by examining the behavioral effects of a series of NPY receptor agonists including NPY, peptidc YY (PYY), the NPY fragment 2–36 (NPY2–36), the Y1 agonist [Leu31, Pro34]-NPY and the Y2 agonist NPY fragment 13–36 (NPY13–36), in two established anxiety models in rats: the elevated plus-naze and the fear-potentiated startle procedures. In the elevated plus-maze procedure, i.t. v. PYY (0.07–2.3 nmol), NPY (0.07–2.3 nmol), NPY2–36 (0.07–2.3 nmol). [Leu31, Pro34]-NPY (0.7–7 nmol), but not NPY13–36 (0.7–7 nmol), increased preference for the open arms of the plus-maze in a dose-dependent manner. In an acoustic startle paradigm, NPY, PYY and NPY2–36 inhibited fear-potentiated startle over the dose-range of 0.23–2.3 nmol. [Leu31, Pro34]-NPY (2.3–13.2 nmol) also attenuated fear-potentiated startle, whereas NPY13–36 (up to 13.2 nmol) had no effect. Taken together, these findings demonstrate that NPY, PYY and NPY2–36 have anxiolytic-like effects that are likely mediated by Y1 receptors.
Ethanolamine is a co‐mitogenic factor for proliferation of primary hepatocytes

Mature adult parenchymal hepatocytes can enter the S phase in the presence of growth factors such as HGF and EGF, but rarely proliferate in culture. We hypothesized that the cell cycle of hepatocytes in culture is restricted before G2/M phase and we attempted to identify the factor that induces cell cycle progression. We found that the conditioned medium from long‐term cultured hepatocytes contained co‐mitogenic activity with other growth factors, which was attributed to ethanolamine (Etn). Etn induced not only DNA synthesis but also cell replication of cultured hepatocytes with various other growth factors. Etn and HGF synergistically induced cyclin D1, A and B expression, however, only cyclin B but not cyclin A formed a complex with Cdc2. In addition, Etn combined with HGF enhanced PKCβII expression and translocated PKCβII to the plasma membrane, and induced filopodia formation, which was inhibited by an antisense oligonucleotide against PKCβII. In addition, blocking the cytoskeleton rearrangement with inhibitors (colchicine, cytochalasin D, or chlerythrine (a specific PKC inhibitor)) inhibited cyclin expression and cell proliferation. Although Etn enhanced the downstream product, cellular phosphatidylethanolamine (PE), PE itself did not show any Etn‐like activities on hepatocytes. Taken together, our results indicate that Etn functions as a co‐replication factor to promote the cell cycle of mature hepatocytes to G2/M phase in the presence of growth factors. The activity is thought to be mediated by PKCβII‐dependent cyclin B expression. J. Cell. Biochem. 84: 249–263, 2002. © 2001 Wiley‐Liss, Inc.
Increased error-related brain activity in pediatric obsessive-compulsive disorder before and after treatment.

OBJECTIVE The error-related negativity is a negative deflection in the event-related potential maximal approximately 50 msec after the commission of errors. The error-related negativity is generated in the anterior cingulate cortex, and both anterior cingulate cortex hyperactivity and increased error-related brain activity have been reported in adults with obsessive-compulsive disorder (OCD). However, no study to date, to the authors' knowledge, has examined error-related brain activity in pediatric patients with OCD, and no study has examined error-related brain activity in OCD both before and after treatment. METHOD The error-related negativity was measured in 18 treatment-seeking pediatric patients with OCD and 18 age-matched comparison subjects. Of these patients, 10 returned for a second testing session after cognitive behavior therapy; 13 comparison children participated a second time after a comparable interval. RESULTS In the pretreatment group, the error-related negativity was reliably larger in pediatric patients with OCD in relation to comparison subjects. This difference was also evident after treatment. There was no relationship between error-related negativity and symptom severity or changes in symptom severity. CONCLUSIONS Consistent with studies in adult patients, increased error-related brain activity is evident in pediatric patients with OCD. Furthermore, increased error-related brain activity does not appear to change as a function of symptom reduction after therapy. These results suggest that an increased error-related negativity may be a trait-like marker for psychopathology and might be a useful endophenotype.
Abdominal Pain–Predominant Functional Gastrointestinal Diseases in Children and Adolescents: Prevalence, Symptomatology, and Association With Emotional Stress

Background and Objective: Functional gastrointestinal disorders (FGD) are common among children, but little is known regarding their prevalence in developing countries. We assessed the prevalence of abdominal pain–predominant FGD, in addition to the predisposing factors and symptomatology, in Sri Lankan children. Patients and Methods: A cross-sectional survey was conducted among a randomly selected group of 10- to 16-year-olds in 8 randomly selected schools in 4 provinces in Sri Lanka. A validated, self-administered questionnaire was completed by children independently in an examination setting. FGD were diagnosed using Rome III criteria. Results: A total of 2180 questionnaires were distributed and 2163 (99.2%) were included in the analysis (1189 [55%] boys, mean age 13.4 years, standard deviation 1.8 years). Of them, 270 (12.5%) had at least 1 abdominal pain–predominant FGD. Irritable bowel syndrome (IBS) was seen in 107 (4.9%), functional dyspepsia in 54 (2.5%), functional abdominal pain in 96 (4.4%), and abdominal migraine (AM) in 21 (1.0%) (2 had AM and functional dyspepsia, 6 had AM and IBS). Extraintestinal symptoms were more common among affected children (P < 0.05). Abdominal pain–predominant FGD were higher in girls and those exposed to stressful events (P < 0.05). Prevalence negatively correlated with age (r = −0.05, P = 0.02). Conclusions: Abdominal pain–predominant FGD affects 12.5% of children ages 10 to 16 years and constitutes a significant health problem in Sri Lanka. IBS is the most common FGD subtype present. Abdominal pain–predominant FGD are higher in girls and those exposed to emotional stress. Prevalence of FGD decreased with age. Extraintestinal symptoms are more frequent in affected children.
Complexation of retroviruses with charged polymers enhances gene transfer by increasing the rate that viruses are delivered to cells

We have previously found that retrovirus transduction is enhanced when an anionic polymer (chondroitin sulfate C) is added to virus stocks that contain an equal weight concentration of a cationic polymer (Polybrene). This observation was unexpected given that previous work has shown that cationic polymers enhance transduction while anionic polymers have the opposite effect.
Permeation Studies Comparing Cobra Skin with Human Skin Using Nicotine Transdermal Patches

Cobra skin (Naja Naja Khaotia) was used as a barrier for an in vitro permeation study using nicotine. Fluxes of nicotine that permeated from Nicotinell ® through cobra skin (CS) taken from the head, body, and tail were 233.93 ± 16.08, 206.87 ± 19.00, and 211.26 ± 22.93 μg/cm2/hr1/2, respectively (n=6). This indicated no significant difference (p >. 05). Abdominal human epidermis (HE), obtained from cadavers, and the CS provided identical permeation kinetics for nicotine, which can be described by Mt = 4Mα=(Dt π L2)1/2. The mean flux of nicotine formulated as an acrylic transdermal patch that permeated through HE was 137.92 ± 67.79 μg/cm2/hr1/2 (4 specimens, n= 12), whereas that through CS was 180.13 ± 41.05 μg/cm2/hr1/2 (4 specimens, n= 15). The ratio of the fluxes of nicotine from formulated patches having three different nicotine contents using CS and HE was 1.22 to 1, respectively, for each of the patches irrespective of nicotine content. The coefficients of variation of the nicotine permeated were 22.79% and 49.15% for CS and HE, respectively, that is, a narrower variation of results was obtained with CS. This indicated that CS could be used for nicotine permeation studies.
Thermophysical Characterization of MgCl2·6H2O, Xylitol and Erythritol as Phase Change Materials (PCM) for Latent Heat Thermal Energy Storage (LHTES)

The application range of existing real scale mobile thermal storage units with phase change materials (PCM) is restricted by the low phase change temperature of 58 ∘C for sodium acetate trihydrate, which is a commonly used storage material. Therefore, only low temperature heat sinks like swimming pools or greenhouses can be supplied. With increasing phase change temperatures, more applications like domestic heating or industrial process heat could be operated. The aim of this study is to find alternative PCM with phase change temperatures between 90 and 150 ∘C. Temperature dependent thermophysical properties like phase change temperatures and enthalpies, densities and thermal diffusivities are measured for the technical grade purity materials xylitol (C5H12O5), erythritol (C4H10O4) and magnesiumchloride hexahydrate (MCHH, MgCl2·6H2O). The sugar alcohols xylitol and erythritol indicate a large supercooling and different melting regimes. The salt hydrate MgCl2·6H2O seems to be a suitable candidate for practical applications. It has a melting temperature of 115.1 ± 0.1 ∘C and a phase change enthalpy of 166.9 ± 1.2 J/g with only 2.8 K supercooling at sample sizes of 100 g. The PCM is stable over 500 repeated melting and solidification cycles at differential scanning calorimeter (DSC) scale with only small changes of the melting enthalpy and temperature.
Correlation of pathological grade and tumor stage of urothelial carcinomas with CD109 expression

Bladder cancer is one of the most common malignant diseases. Since a high‐rate of recurrence is a serious problem for early stage urothelial carcinomas, new strategies for the management of recurrent urothelial carcinomas have been explored. CD109 is a glycosylphosphatidylinositol‐anchored glycoprotein and is expressed in various cancer tissues, mainly squamous cell carcinomas. CD109 negatively controls transforming growth factor (TGF)‐β/Smad signaling in vitro. In this study, we analyzed the clinical significance of CD109 expression in bladder cancer using immunohistochemistry. Of 156 urothelial carcinoma tissues, 69.9% were positive for CD109, whereas CD109 was not expressed in seven normal bladder epithelia. CD109 expression was significantly higher in non‐muscle‐invasive (pTa+pT1) or low‐grade (G1+G2) tumors than in muscle‐invasive (pT2‐4) or high‐grade (G3) tumors, and was associated with cancer‐specific survival. Simultaneous immunostaining of CD109 and phosphorylated Smad2 showed an inverse immunoreactivity relationship between the two, suggesting that CD109 inhibits TGF‐β/Smad signaling in tumor tissues. Interestingly, CD109 was found to be highly expressed in the basal layer of non‐invasive urothelial carcinomas, and the expression pattern was similar to that of CD44, a marker of cancer stem cells. These findings suggest that CD109 is involved in bladder tumorigenesis and is a potential target for cancer immunotherapy.
Bilateral Retinal Vasculopathy Associated with Autosomal Dominant Dyskeratosis Congenita

Purpose To report a case of autosomal dominant dyskeratosis congenita (AD-DC) complicated by bilateral retinal vasculopathy and proliferative retinopathy with vitreous hemorrhage in the right eye, in the absence of pancytopenia. Methods We report a 32-year-old woman who presented with floaters in her right eye. She underwent complete ophthalmic examination and fundus fluorescein angiography. Results Funduscopic examination revealed vascular sheathing in the temporal periphery of both eyes and a vitreous hemorrhage in the right eye. Fluorescein angiography showed retinal neovascularization in the right eye and bilateral temporal peripheral capillary nonperfusion. Treatment consisted of laser photocoagulation directed to the areas of capillary nonperfusion in both eyes. A point mutation in the TERC gene confirmed the diagnosis of AD-DC. Conclusions Autosomal dominant dyskeratosis congenita is a rare form of inherited bone marrow failure and its presentation is milder than seen in patients with X-linked and autosomal recessive mutations. These patients may lack the classic clinical triad, so it is important to have a high index of suspicion and to be aware of retinal vasculopathy as a complication of dyskeratosis congenita as it may severely compromise vision. Appropriate treatment includes prompt laser photocoagulation to areas of retinal nonperfusion.
Retinal detachment in Olmsted County, Minnesota, 1976 through 1995.

OBJECTIVE To estimate the incidence of rhegmatogenous retinal detachment (RD) in a geographically defined population and to compare the probability of RD in residents after cataract extraction with the probability of RD in residents who did not have cataract extraction. DESIGN Rochester Epidemiology Project databases were used to perform a retrospective population-based incidence study of RD diagnosed between 1976 and 1995 with cohort analyses of the influence of risk factors on the occurrence of RD. PARTICIPANTS The population of Olmsted County, Minnesota, participated. MAIN OUTCOME MEASURE Incidence rates of RD adjusted to the age and gender distribution of the 1990 U.S. white population were measured. RESULTS Three hundred eleven incident cases of rhegmatogenous RD were identified. The mean annual age- and gender-adjusted incidence rate of rhegmatogenous RD was 17.9 per 100,000 persons (95% confidence interval [CI], 15.9-19.9). For idiopathic rhegmatogenous RD alone, the mean annual age- and gender-adjusted incidence rate was 12.6 (95% CI, 10.9-14.3) per 100,000 persons. Ten years after phacoemulsification and extracapsular cataract extraction, the estimated cumulative probability of RD was 5.5 (95% CI, 3.4-7.6) times as high as would have been expected in a similar group of county residents not undergoing cataract surgery. CONCLUSIONS Cataract surgery is associated with a significantly elevated long-term cumulative probability of retinal detachment.
A Novel Mutation Pattern Emerging during Lamivudine Treatment Shows Cross-Resistance to Adefovir Dipivoxil Treatment

Aims This study was conducted to clarify the resistance profile of a novel mutation pattern emerging during lamivudine (3TC) therapy and showing cross-resistance to adefovir dipivoxil (ADV) in a patient with chronic hepatitis B. Methods and results Successful suppression of hepatitis B virus (HBV) replication by sequential therapy of 9 MU thrice weekly interferon (IFN) and 3TC was followed by genotypical resistance detected at month 28 of therapy (month 19 of lamivudine treatment). ADV was added to 3TC therapy on month 44 of antiviral treatment. Neither alanine aminotransferase normalization nor a stable decrease in HBV viral load was observed, although ADV was used for more than 40 months. The HBV pol region was amplified from serum samples obtained before and after ADV treatment. The complete genome was cloned into a TA vector. PCR products and 7–10 clones from each cloned vector were sequenced. A novel mutation, A181S, in the reverse transcriptase gene leading to a conversion of W172C in the overlapping surface antigen gene was detected along with a M204I mutation. The complete genome comprising the A181S+M204I pattern was cloned into an expression vector and its in vitro susceptibility to 3TC, ADV, tenofovir (PMPA), clevudine (l-FMAU) and emtricitabine (FTC) were determined in transiently transfected Huh7 cells. This mutation pattern displayed more than 1,000-fold resistance to the nucleoside analogues 3TC and FTC and approximately sixfold resistance to l-FMAU, while it confers 28.23- and 5.57-fold resistance for the nucleotide analogues ADV and PMPA, respectively. Conclusion A new mutation pattern, A181S+M204I, arising under lamivudine treatment confers cross-resistance to ADV both in vivo and in vitro.
Prenatal factors associated with the development of eczema in the first year of life

Prenatal factors have been implicated in childhood eczema, but the relationship between maternal cytokine production during pregnancy and infant eczema is unknown. Non‐selected women in their third trimester were enrolled in the Tucson Infant Immune Study. Data from three sources were used to define MD‐eczema: parent‐completed illness questionnaires at age 2, 3, 4, 6 and 9 months regarding physician‐seen eczema, parent‐completed questionnaires at 12 months regarding physician‐diagnosed eczema, and medical record reviews. Blood samples were taken from mothers during their third trimester and from the umbilical cord at birth. Maternal peripheral blood mononuclear cells and cord blood mononuclear cells were stimulated with ConA/PMA, and supernatants were assayed for IFN‐γ and IL‐4, ‐5, ‐10, and ‐13. Of 364 children, 28% were seen by a physician for eczema by 1 yr of age. After adjustment for potential confounders using logistic regression, the odds for development of eczema in infancy were significantly higher when mothers had active eczema in pregnancy (OR, 2.46, CI 1.0–5.8, p < 0.042) and when mothers were in the highest tertile of serum IgE production (OR 2.28, CI 1.2–4.4, p < 0.013). Colds in the third trimester were associated with lower odds of eczema (OR 0.32, CI 0.16–0.63, p < 0.001). Our findings from this cohort study suggest that in utero factors, including maternal IgE, colds, and eczema, may influence the risk of infant eczema.
Associations Between Viral and Bacterial Potential Pathogens in the Nasopharynx of Children With and Without Respiratory Symptoms

Background: Nasopharyngeal (NP) bacterial colonization is necessary for subsequent respiratory and/or invasive infection. Our study aimed at comparing NP bacterial colonization rates between children with and without symptoms of an acute viral respiratory tract infection and examining associations between identified microorganisms. Methods: Children 3 months to 6 years of age with and without an acute viral respiratory tract infection were recruited, and a questionnaire was filled. NP samples were examined for Streptococcus pneumoniae (SP), Haemophilus influenzae (HI), Moraxella catarrhalis (MC), Staphylococcus aureus and Streptococcus pyogenes by culture. Viruses were detected with polymerase chain reaction. Results: Median age of the 386 recruited children was 23.4 months, and 127 had no respiratory symptoms. More asymptomatic subjects were found negative for all bacteria tested (P < 0.01). SP (P < 0.01), MC (P = 0.001) and mixed bacterial colonization patterns were more frequent among symptomatic children (P < 0.05). Colonization of symptomatic, virus-positive children with MC was higher than in asymptomatic and/or virus-negative children (P = 0.005). The highest HI and MC colonization rates were recorded in association with influenza virus. A strongly negative association between SP and S. aureus, a higher rate of HI detection among SP colonized children and an increased likelihood of MC detection in the presence of HI were observed. HI colonization was more likely in the presence of respiratory syncytial virus and MC colonization was associated with rhinovirus detection. Conclusions: Viruses are associated with different NP bacterial colonization patterns. Observed pathogens’ associations may play a role in disease, and continuous surveillance is required to follow possible effects of interventions such as vaccines.
High Maternal Serum Alpha-Fetoprotein and Low Birthweight

Maternal serum alpha-fetoprotein (AFP) levels between 15 and 19 weeks gestation were studied in relation to birthweight, gestational age, maternal weight, and daily cigarette consumption in 1739 pregnancies. All infants were born after the 28th week of gestation and all were without neural tube defects. Gestational age was estimated by early measurement of the fetal biparietal diameter. High maternal serum AFP, low maternal weight, and the number of cigarettes smoked per day were found to correlate with low birthweight, but not with gestational age. By testing the influence of the individual parameters on the subsequent birthweight, no significant correlation was found between the AFP levels and birthweight. Low birthweight was mainly a result of cigarette smoking and low maternal weight. Screening for AFP in the second trimester, therefore, seems to be of no value in predicting low birthweight when maternal weight is taken into consideration.
Angiotensin II AT1 receptor blockade selectively enhances brain AT2 receptor expression, and abolishes the cold-restraint stress-induced increase in tyrosine hydroxylase mRNA in the locus coeruleus of spontaneously hypertensive rats

Spontaneously hypertensive rats, a stress-sensitive strain, were pretreated orally for 14 days with the AT1 receptor antagonist candesartan before submission to 2 h of cold-restraint stress. In non-treated rats, stress decreased AT1 receptor binding in the median eminence and basolateral amygdala, increased AT2 receptor binding in the medial subnucleus of the inferior olive, decreased AT2 binding in the ventrolateral thalamic nucleus and increased tyrosine hydroxylase mRNA level in the locus coeruleus. In non-stressed rats, AT1 receptor blockade reduced AT1 receptor binding in all areas studied and enhanced AT2 receptor binding in the medial subnucleus of the inferior olive. Candesartan pretreatment produced a similar decrease in brain AT1 binding after stress, and prevented the stress-induced AT2 receptor binding decrease in the ventrolateral thalamic nucleus. In the locus coeruleus and adrenal medulla, AT1 blockade abolished the stress-induced increase in tyrosine hydroxylase mRNA level. Our results demonstrate that oral administration of candesartan effectively blocked brain AT1 receptors, selectively increased central AT2 receptor expression and prevented the stress-induced central stimulation of tyrosine hydroxylase transcription. The present results support a role of brain AT1 and AT2 receptors in the regulation of the stress response, and the hypothesis that AT1 receptor antagonists may be considered as potential therapeutic compounds in stress related disorders in addition to their anti-hypertensive properties.
Topiramate Use in Pediatric Patients

ABSTRACT: Topiramate (TPM), a new antiepileptic medication, is efficacious as adjunctive therapy in adults with partial onset seizures. Its efficacy as adjunctive therapy in children was evaluated in two randomized double-blind placebo-controlled trials involving childhood epileptic encephalopathy (the Lennox-Gastaut syndrome) and partial onset seizures. In these studies, topiramate adjunctive therapy resulted in a significant reduction in drop attacks (tonic or atonic seizures) in patients with the Lennox Gastaut syndrome and a significant reduction in partial onset seizures in children with refractory partial epilepsy. In both trials, TPM's efficacy improved as the dose escalated from the double-blind phase to the open-label portion. The minimally effective topiramate dose for adjunctive therapy in children with refractory epilepsy appears to be 6 mg/kg/day. Topiramate was well tolerated with mild or moderate side effects, predominantly related to the central nervous system. Practical tips are provided that may increase the chance that topiramate will be effective and well tolerated. The most important advice is a “start low, go slow” approach. An initial TPM dose of 0.5 - 1 mg/kg/day followed by weekly increments of 0.5 - 1 mg/kg is usually well tolerated. Based on these studies, topiramate appears to be an important addition to our pediatric AED armamentarium.