bluuebunny/crossref_metadata_2025_split huggingface dataset:
Isoflurane depresses hippocampal CA1 glutamate nerve terminals without inhibiting fiber volleys
Authors: Winegar Bruce D , MacIver M Bruce 
Published: January 2006

AbstractBackgroundAnesthetic-induced CNS depression is thought to involve reduction of glutamate release from nerve terminals. Recent studies suggest that isoflurane reduces glutamate release by block of Na channels. To further investigate this question we examined the actions of isoflurane, TTX, extracellular Ca2+, CNQX and stimulus voltage (stim) on glutamate-mediated transmission at hippocampal excitatory synapses. EPSPs were recorded from CA1 neurons in rat hippocampal brain slices in response to Schaffer-collateral fiber stimulation.ResultsIsoflurane (350 μM; 1 MAC) reversibly depressed EPSP amplitudes by ~60% while facilitation increased ~20%. Consistent with previous studies, these results indicate a presynaptic site of action that involves reduced excitation-release coupling. EPSPs were depressed to comparable levels by TTX (60 nM) or lowered stim, but facilitation was not changed, indicating a simple failure of axonal conduction. Similarly, partial antagonism of postsynaptic glutamate receptors with CNQX (10 μM) depressed EPSP amplitudes with no change in facilitation. However, EPSP depression by low external Ca2+(0.8 mM) was accompanied by an increase in facilitation comparable to isoflurane. Isoflurane depression of EPSP amplitudes could also be partly reversed by high external Ca2+(4 mM) that also decreased facilitation. Isoflurane or low Ca2+markedly reduced the slopes of fiber volley (FV)-EPSP input-output curves, consistent with little or no effect on FVs. By contrast, TTX didn't alter the FV-EPSP curve slope, indicating that EPSP depression resulted from FV depression. FVs were remarkably resistant to isoflurane. Somatic spike currents were unaffected by 350 μM (1 MAC) isoflurane as well. The EC50for isoflurane depression of FVs was ~2.8 mM (12 vol. %; 8 MAC).ConclusionIsoflurane appears to depress CA1 synapses at presynaptic sites downstream from Na channels, as evident by the increased facilitation that accompanies EPSP depression. Fiber volleys did not exhibit depression by isoflurane, as has been reported for other brain regions.
Impact of ε and θ subunits on pharmacological properties of α3β1 GABAA receptors expressed in Xenopus oocytes
Authors: Ranna Martin , Sinkkonen Saku T , Möykkynen Tommi , Uusi-Oukari Mikko , Korpi Esa R 
Published: January 2006

AbstractBackgroundγ-Aminobutyric acid type A (GABAA) receptors provide the main inhibitory control in the brain. Their heterogeneity may make it possible to precisely target drug effects to selected neuronal populations.In situhybridization using rat brain sections has revealed a unique expression of GABAAreceptor ε and θ subunit transcripts in the locus coeruleus, where they are accompanied at least by α3, α2, β1 and β3 subunits. Here, we studied the pharmacology of the human α3β1, α3β1ε, α3β1θ and α3β1εθ receptor subtypes expressed inXenopusoocytes and compared them with the γ2 subunit-containing receptors.ResultsThe GABA sensitivites and effects of several positive modulators of GABAAreceptors were studied in the absence and the presence of EC25GABA using the two-electrode voltage-clamp method. We found 100-fold differences in GABA sensitivity between the receptors, α3β1ε subtype being the most sensitive and α3β1γ2 the least sensitive. Also gaboxadol dose-response curves followed the same sensitivity rank order, with EC50values being 72 and 411 μM for α3β1ε and α3β1γ2 subtypes, respectively. In the presence of EC25GABA, introduction of the ε subunit to the receptor complex resulted in diminished modulatory effects by etomidate, propofol, pregnanolone and flurazepam, but not by pentobarbital. Furthermore, the α3β1ε subtype displayed picrotoxin-sensitive spontaneous activity. The θ subunit-containing receptors were efficiently potentiated by the anesthetic etomidate, suggesting that θ subunit could bring the properties of β2 or β3 subunits to the receptor complex.ConclusionThe ε and θ subunits bring additional features to α3β1 GABAAreceptors. These receptor subtypes may constitute as novel drug targets in selected brain regions, e.g., in the brainstem locus coeruleus nuclei.
Muscle fiber-type distribution predicts weight gain and unfavorable left ventricular geometry: a 19 year follow-up study
Authors: Karjalainen Jouko , Tikkanen Heikki , Hernelahti Miika , Kujala Urho M 
Published: January 2006

Abstract

Background
Skeletal muscle consists of type-I (slow-twitch) and type-II (fast-twitch) fibers, with proportions highly variable between individuals and mostly determined by genetic factors. Cross-sectional studies have associated low percentage of type-I fibers (type-I%) with many cardiovascular risk factors.

Methods
We investigated whether baseline type-I% predicts left ventricular (LV) structure and function at 19-year follow-up, and if so, which are the strongest mediating factors. At baseline in 1984 muscle fiber-type distribution (by actomyosin ATPase staining) was studied in 63 healthy men (aged 32–58 years). The follow-up in 2003 included echocardiography, measurement of obesity related variables, physical activity and blood pressure.

Results
In the 40 men not using cardiovascular drugs at follow-up, low type-I% predicted higher heart rate, blood pressure, and LV fractional shortening suggesting increased sympathetic tone. Low type-I% predicted smaller LV chamber diameters (P ≤ 0.009) and greater relative wall thickness (P = 0.034) without increase in LV mass (concentric remodeling). This was explained by the association of type-I% with obesity related variables. Type-I% was an independent predictor of follow-up body fat percentage, waist/hip ratio, weight gain in adulthood, and physical activity (in all P ≤ 0.001). After including these risk factors in the regression models, weight gain was the strongest predictor of LV geometry explaining 64% of the variation in LV end-diastolic diameter, 72% in end-systolic diameter, and 53% in relative wall thickness.

Conclusion
Low type-I% predicts obesity and weight gain especially in the mid-abdomen, and consequently unfavourable LV geometry indicating increased cardiovascular risk.
Left ventricular geometric patterns in newly presenting nigerian hypertensives: An echocardiographic study
Authors: Aje Akinyemi , Adebiyi Adewole A , Oladapo Olulola O , Dada Adekola , Ogah Okechukwu S , Ojji Dike B , Falase Ayodele O 
Published: January 2006

Abstract

Background
Hypertension is a global problem and it is prevalent in Nigeria. Left ventricular hypertrophy is a major complication of hypertension with risk of sudden death and arrhythmias among others. Abnormal left ventricular geometric patterns also increase the burden of morbidity and mortality. It is therefore important to know the different left ventricular geometric patterns in Nigerian hypertensives because of their prognostic significance.

Methods
One hundred (100) newly presenting hypertensives (53 males and 47 females) and 100 controls (53 males and 47 females) were recruited for the study. All were subjected to clinical evaluation and full echocardiographic examination was performed according to the ASE recommendation. The relative wall thickness and the presence or absence of echocardiographic left ventricular hypertrophy were used to determine the various geometric patterns

Results
The mean age of the hypertensive subjects was 56.06 (± 7.68) years while that of the control subjects was 56.10 (± 7.68) years. There was no significant difference in the mean ages of the two groups. In the hypertensive subjects 28% had normal geometry, 26% had concentric remodeling, 28% had concentric hypertrophy and 18% had eccentric hypertrophy. In the control group, 86% had normal geometry, 11% had concentric remodeling, 3% had eccentric hypertrophy and none had concentric hypertrophy. There was statistical significance when the geometric patterns of the hypertensive and controls were compared (χ2 = 74.30, p value < 0.0001).

Conclusion
The study showed that only 28% of the hypertensive subjects had normal LV geometric pattern while 86% of the normal subjects had normal geometry. There is need for longitudinal studies in order to prognosticate the various geometric patterns.
Management and outcome of bleeding pseudoaneurysm associated with chronic pancreatitis
Authors: Hsu Jun-Te , Yeh Chun-Nan , Hung Chien-Fu , Chen Han-Ming , Hwang Tsann-Long , Jan Yi-Yin , Chen Miin-Fu 
Published: January 2006

Abstract

Background
A bleeding pseudoaneurysm in patients with chronic pancreatitis is a rare and potentially lethal complication. Optimal treatment of bleeding peripancreatic pseudoaneurysm remains controversial. This study reports on experience at Chang Gung Memorial Hospital (CGMH) in managing of bleeding pseudoaneurysms associated with chronic pancreatitis.

Methods
The medical records of 9 patients (8 males and 1 female; age range, 28 – 71 years; median, 36 years) with bleeding pseudoaneurysms associated with chronic pancreatitis treated at CGMH between Aug. 1992 and Sep. 2004 were retrospectively reviewed. Alcohol abuse (n = 7;78%) was the predominant predisposing factor. Diagnoses of bleeding pseudoaneurysms were based on angiographic (7/7), computed tomographic (4/7), ultrasound (2/5), and surgical (2/2) findings. Whether surgery or angiographic embolization was performed was primarily based on patient clinical condition. Median follow-up was 38 months (range, 4 – 87 months).

Results
Abdominal computed tomography revealed bleeding pseudoaneurysms in 4 of 7 patients (57%). Angiography determined correct diagnosis in 7 patients (7/7, 100%). The splenic artery was involved in 5 cases, the pancreaticoduodenal artery in 2, the gastroduodenal artery in 1, and the middle colic artery in 1. Initial treatment was emergency (n = 4) or elective (n = 3) surgery in 7 patients and arterial embolization in 2. Rebleeding was detected after initial treatment in 3 patients. Overall, 5 arterial embolizations and 9 surgical interventions were performed; the respective rates of success of these treatments were 20% (1/5) and 89% (8/9). Five patients developed pseudocysts before treatment (n = 3) or following intervention (n = 2). Pseudocyst formation was identified in 2 of the 3 rebleeding patients. Five patients underwent surgical treatment for associated pseudocysts and bleeding did not recur. One patient died from angiography-related complications. Overall mortality rate was 11% (1/9). Surgery-related mortality was 0%.

Conclusion
Angiography is valuable in localizing bleeding pseudoaneurysms. In this limited series, patients with bleeding pseudoaneurysms associated with chronic pancreatitis treated surgically seemingly obtained good outcomes.
Sexually transmitted infections in Saudi Arabia
Authors: Madani Tariq A 
Published: January 2006

Abstract

Background
Data on sexually transmitted infections (STIs) in Saudi Arabia (SA) and other Islamic countries are limited. This study describes the results of a five-year surveillance for STIs in SA.

Methods
This is a case series descriptive study of all confirmed STIs diagnosed in SA from January, 1995 through December, 1999.

Results
A total of 39049 STIs were reported to the Ministry of Health. Reported STIs included nongonococcal urethritis (14557 infections, 37.3%), trichomoniasis (10967 infections, 28.1%), gonococcal urethritis (5547 infections, 14.2%), syphilis (3385 infections, 8.7%), human immunodeficiency virus (2917 infections, 7.5%), genital warts (1382, 3.5%), genital herpes (216 infections, 0.6%), and chancroid (78 infections, 0.2%). The average annual incidence of STIs per 100,000 population for Saudis and non-Saudis, respectively, was as follows: 14.8 and 7.5 for nongonococcal urethritis, 9.4 and 10.4 for trichomoniasis, 5.2 and 4.2 for gonorrhea, 1.7 and 6.4 for syphilis, 0.6 and 8.0 for HIV, 1.4 and 0.7 for genital warts, 0.1 and 0.4 for genital herpes, and 0.1 and 0.1 for chancroid. The incidence of STIs was somewhat steady over the surveillance period except for nongonococcal urethritis which gradually increased.

Conclusion
Nongonococcal urethritis, trichomoniasis, and gonococcal urethritis were the most commonly reported STIs in SA. Even though the incidence of STIs in SA is limited, appropriate preventive strategies that conform to the Islamic rules and values are essential and should be of highest priority for policymakers because of the potential of such infections to spread particularly among the youth.
Comparative evidence for a link between Peyer's patch development and susceptibility to transmissible spongiform encephalopathies
Authors: St Rose Suzanne G , Hunter Nora , Matthews Louise , Foster James D , Chase-Topping Margo E , Kruuk Loeske EB , Shaw Darren J , Rhind Susan M , Will Robert G , Woolhouse Mark EJ 
Published: January 2006

Abstract

Background
Epidemiological analyses indicate that the age distribution of natural cases of transmissible spongiform encephalopathies (TSEs) reflect age-related risk of infection, however, the underlying mechanisms remain poorly understood. Using a comparative approach, we tested the hypothesis that, there is a significant correlation between risk of infection for scrapie, bovine spongiform encephalopathy (BSE) and variant CJD (vCJD), and the development of lymphoid tissue in the gut.

Methods
Using anatomical data and estimates of risk of infection in mathematical models (which included results from previously published studies) for sheep, cattle and humans, we calculated the Spearman's rank correlation coefficient, rs, between available measures of Peyer's patch (PP) development and the estimated risk of infection for an individual of the corresponding age.

Results
There was a significant correlation between the measures of PP development and the estimated risk of TSE infection; the two age-related distributions peaked in the same age groups. This result was obtained for each of the three host species: for sheep, surface area of ileal PP tissue vs risk of infection, rs = 0.913 (n = 19, P < 0.001), and lymphoid follicle density vs risk of infection, rs = 0.933 (n = 19, P < 0.001); for cattle, weight of PP tissue vs risk of infection, rs = 0.693 (n = 94, P < 0.001); and for humans, number of PPs vs risk of infection, rs = 0.384 (n = 46, P = 0.008). In addition, when changes in exposure associated with BSE-contaminated meat were accounted for, the two age-related patterns for humans remained concordant: rs = 0.360 (n = 46, P = 0.014).

Conclusion
Our findings suggest that, for sheep, cattle and humans alike there is an association between PP development (or a correlate of PP development) and susceptibility to natural TSE infection. This association may explain changes in susceptibility with host age, and differences in the age-susceptibility relationship between host species.
Clinical features and outcome of sporadic serogroup W135 disease Taiwan
Authors: Wang Jiun-Ling , Liu Ding-Ping , Yen Jer-Jea , Yu Chia-Jung , Liu Hsi-Chen , Lin Ching-Yuang , Chang Shan-Chwen 
Published: January 2006

Abstract

Background
Few published reports have evaluated the clinical features and outcome of serogroup W135 meningococcal disease. In Taiwan, W135 is the second most prevalent meningococcal disease serogroup.

Method
A nationwide study was conducted to retrospectively analyze epidemiologic data from 115 patients with laboratory confirmed meningococcal disease that occurred from 2001 through 2003.

Results
Serogroup W135 accounted for 26% of all cases and most (76.7%) were older than 20 years. There were no cases of serogroup W135 meningococcal disease associated with Hajj pilgrims, and all cases were sporadic. In 88 patients with complete case records, we compared the presenting symptoms, signs, laboratory data, and outcomes between W135 and non-W135 patients. There were no differences in presenting symptoms except for the higher prevalence of pneumonia found in W135 patients (23.8% vs. 1.5%; OR: 20.6; 95%CI: 2.3–189.0; p = 0.003). The distribution of inflammatory cells in CSF in patients with meningitis was also different between W135 and non-W135 patients. W135 patients had a trend toward more intubations and shock but it did not achieve statistical significance. In multivariate analysis of factors associated with death, three independent factors were found: bacteremia without meningitis, altered mental status, and petechiae or purpura on admission.

Conclusion
Sporadic serogroup W135 meningococcal disease is an important component of the meningococcal disease burden in Taiwan, but it is not directly associated with Hajj pilgrims. Compared with patients infected by other serogroups of meningococci, patients with serogroup W135 were older and more likely to have extrameningeal involvement such as pneumonia.
Microsatellite instability analysis in hereditary non-polyposis colon cancer using the Bethesda consensus panel of microsatellite markers in the absence of proband normal tissue
Authors: Chialina Sergio G , Fornes Claudia , Landi Carolina , de La Vega Elena Carlos D , Nicolorich Maria V , Dourisboure Ricardo J , Solano Angela , Solis Edita A 
Published: January 2006

Abstract

Background
Hereditary non-polyposis colon cancer (HNPCC) is an autosomal dominant syndrome predisposing to the early development of various cancers including those of colon, rectum, endometrium, ovarium, small bowel, stomach and urinary tract. HNPCC is caused by germline mutations in the DNA mismatch repair genes, mostly hMSH2 or hMLH1.
In this study, we report the analysis for genetic counseling of three first-degree relatives (the mother and two sisters) of a male who died of colorectal adenocarcinoma at the age of 23. The family fulfilled strict Amsterdam-I criteria (AC-I) with the presence of extracolonic tumors in the extended pedigree. We overcame the difficulty of having a proband post-mortem non-tumor tissue sample for MSI testing by studying the alleles carried by his progenitors.

Methods
Tumor MSI testing is described as initial screening in both primary and metastasis tumor tissue blocks, using the reference panel of 5 microsatellite markers standardized by the National Cancer Institute (NCI) for the screening of HNPCC (BAT-25, BAT-26, D2S123, D5S346 and D17S250). Subsequent mutation analysis of the hMLH1 and hMSH2 genes was performed.

Results
Three of five microsatellite markers (BAT-25, BAT-26 and D5S346) presented different alleles in the proband's tumor as compared to those inherited from his parents. The tumor was classified as high frequency microsatellite instability (MSI-H). We identified in the HNPCC family a novel germline missense (c.1864C>A) mutation in exon 12 of hMSH2 gene, leading to a proline 622 to threonine (p.Pro622Thr) amino acid substitution.

Conclusion
This approach allowed us to establish the tumor MSI status using the NCI recommended panel in the absence of proband's non-tumor tissue and before sequencing the obligate carrier. According to the Human Gene Mutation Database (HGMD) and the International Society for Gastrointestinal Hereditary Tumors (InSiGHT) Database this is the first report of this mutation.
Cytokeratin 8/18 expression indicates a poor prognosis in squamous cell carcinomas of the oral cavity
Authors: Fillies Thomas , Werkmeister Richard , Packeisen Jens , Brandt Burkhard , Morin Philippe , Weingart Dieter , Joos Ulrich , Buerger Horst 
Published: January 2006

AbstractBackgroundIntermediary filaments are involved in cell motility and cancer progression. In a variety of organs, the expression of distinct intermediary filaments are associated with patient prognosis. In this study, we seeked to define the prognostic potential of cytokeratin and vimentin expression patterns in squamous cell carcinomas (SCC's) of the oral cavity.Methods308 patients with histologically proven and surgically treated squamous cell carcinomas of the oral cavity were investigated for the immunohistochemical expression of a variety of intermediary filaments including high- and low-molecular weight cytokeratins (Ck's), such as Ck 5/6, Ck 8/18, Ck 1, CK 10, Ck 14, Ck 19 and vimentin, using the tissue microarray technique. Correlations between clinical features and the expression of Cytokeratins and vimentin were evaluated statistically by Kaplan-Meier curves and multivariate Cox regression analysis.ResultsThe expression of Ck 8/18 and Ck 19 were overall significantly correlated with a poor clinical prognosis (Ck 8/18 p = 0.04; Ck19 p < 0.01). These findings could also be reproduced for Ck 8/18 in primary nodal-negative SCC's and held true in multivariate-analysis. No significant correlation with patient prognosis could be found for the expression of the other cytokeratins and for vimentin.ConclusionThe expression of Ck 8/18 in SCC's of the oral cavity is an independent prognostic marker and indicates a decreased overall and progression free survival. These results provide an extended knowledge about the role of intermediary filament expression patterns in SCC's.
Proapoptotic activity of Ukrain is based on Chelidonium majusL. alkaloids and mediated via a mitochondrial death pathway
Authors: Habermehl Daniel , Kammerer Bernd , Handrick René , Eldh Therese , Gruber Charlotte , Cordes Nils , Daniel Peter T , Plasswilm Ludwig , Bamberg Michael , Belka Claus , Jendrossek Verena 
Published: January 2006

AbstractBackgroundThe anticancer drug Ukrain (NSC-631570) which has been specified by the manufacturer as semisynthetic derivative of theChelidonium majusL. alkaloid chelidonine and the alkylans thiotepa was reported to exert selective cytotoxic effects on human tumour cell linesin vitro. Few clinical trials suggest beneficial effects in the treatment of human cancer. Aim of the present study was to elucidate the importance of apoptosis induction for the antineoplastic activity of Ukrain, to define the molecular mechanism of its cytotoxic effects and to identify its active constituents by mass spectrometry.MethodsApoptosis induction was analysed in a Jurkat T-lymphoma cell model by fluorescence microscopy (chromatin condensation and nuclear fragmentation), flow cytometry (cellular shrinkage, depolarisation of the mitochondrial membrane potential, caspase-activation) and Western blot analysis (caspase-activation). Composition of Ukrain was analysed by mass spectrometry and LC-MS coupling.ResultsUkrain turned out to be a potent inducer of apoptosis. Mechanistic analyses revealed that Ukrain induced depolarisation of the mitochondrial membrane potential and activation of caspases. Lack of caspase-8, expression of cFLIP-L and resistance to death receptor ligand-induced apoptosis failed to inhibit Ukrain-induced apoptosis while lack of FADD caused a delay but not abrogation of Ukrain-induced apoptosis pointing to a death receptor independent signalling pathway. In contrast, the broad spectrum caspase-inhibitor zVAD-fmk blocked Ukrain-induced cell death. Moreover, over-expression of Bcl-2 or Bcl-xLand expression of dominant negative caspase-9 partially reduced Ukrain-induced apoptosis pointing to Bcl-2 controlled mitochondrial signalling events.However, mass spectrometric analysis of Ukrain failed to detect the suggested trimeric chelidonine thiophosphortriamide or putative dimeric or monomeric chelidonine thiophosphortriamide intermediates from chemical synthesis. Instead, theChelidonium majusL. alkaloids chelidonine, sanguinarine, chelerythrine, protopine and allocryptopine were identified as major components of Ukrain.Apart from sanguinarine and chelerythrine, chelidonine turned out to be a potent inducer of apoptosis triggering cell death at concentrations of 0.001 mM, while protopine and allocryptopine were less effective. Similar to Ukrain, apoptosis signalling of chelidonine involved Bcl-2 controlled mitochondrial alterations and caspase-activation.ConclusionThe potent proapoptotic effects of Ukrain are not due to the suggested "Ukrain-molecule" but to the cytotoxic efficacy ofChelidonium majusL. alkaloids including chelidonine.