bluuebunny/crossref_metadata_2025 huggingface dataset:
Serotonin and Melatonin Do Not Play a Prominent Role in the Growth of Prostate Cancer Cell Lines
Authors: Pirozhok I. , Meye A. , Hakenberg O.W. , Fuessel S. , Wirth M.P.
Published: May 2010

Objectives: To investigate the effects of serotonin and melatonin (MLT) on the regulation of malignant growth and the activity of serotonin receptors (5HTR1a/-1b) in prostate cancer (PCa) cell lines. Materials and Methods: In four PCa cell lines (LNCaP, 22RV1, PC3, DU145) and two reference cell lines 5HTR1a and -1b, relative mRNA expression levels were assessed. Different serotonin and MLT receptor agonists and antagonists were used in stimulation and inhibition experiments. Results: mRNA expression of 5HTR1b was higher than that of 5HTR1a in all PCa cell lines. Serotonin showed a significant growth stimulatory effect in all PCa lines. The 5HTR1a and -1b agonists/antagonists did not significantly affect viability. MLT inhibited viability only in PC3 cells. Similarly, the 5HTR1a antagonist induced apoptotic changes in PC3 cells only at 10–4M, while the 5HTR1b antagonist induced necrosis at 10–4M in all cell lines. Cell cycle alterations were seen in PC3 and DU145 cells under the influence of the 5HTR1a antagonist. Conclusions: Serotonin receptor antagonists and agonists as well as MLT influence viability and apoptosis of PCa cell lines at supraphysiologic concentrations. In contrast to other reports, our results do not support a regulatory role of serotonin or MLT receptor activation or inhibition in PCa growth.
Addition of Lidocaine Suppositories to Periprostatic Nerve Block Enhances Pain Control in Prostate Biopsies: A Placebo-Controlled Randomized Trial
Authors: Szlauer Roman , Paras Ljiljana , Fink Klaus G.
Published: May 2010

Purpose: The aim of this study was to evaluate the efficacy of a combined topical and local anesthesia consisting of a transrectal lidocaine suppository followed by periprostatic nerve block (PNB) in comparison to the combination of transrectally applied lidocaine gel followed by PNB and PNB alone as methods of reducing pain during transrectal prostate biopsy. Patients and Methods: 100 patients were randomized to four groups and received either a placebo suppository or 10 ml of 2% lidocaine gel or a suppository containing 60 or 120 mg of lidocaine 1 h before biopsy. Additionally, every patient received a PNB using 5 ml 2% lidocaine. After performing an extensive transrectal ultrasound-guided biopsy, pain was evaluated using a visual pain scale. Results: The mean pain score in the placebo group was 3.4, in the lidocaine gel group it was 3.7, and in the 60 or 120 mg lidocaine suppository groups it was 2.4 and 2.5, respectively. No patient showed vegetative symptoms like sweating or symptomatic hypotonia and no patient had severe pain. Conclusion: The addition of lidocaine suppositories to PNB as a form of combined anesthesia showed a significantly better pain reduction than the addition of lidocaine gel to PNB or PNB alone.
Downsizing a Tumor Thrombus of Advanced Renal Cell Carcinoma with Neoadjuvant Systemic Therapy and Resulting Histopathological Effects
Authors: Kroeger N. , Gajda M. , Zanow J. , Petersen I. , Settmacher U. , Wunderlich H. , Steiner T.
Published: May 2010

Background: We report a treatment option in surgical therapy of locally advanced renal cell carcinoma (RCC). Method: A 63-year-old patient with locally advanced RCC including an atrial thrombus underwent 2 cycles of neoadjuvant therapy (Sutent® 50 mg daily for 4 weeks followed by 2 weeks off) and then tumor surgery. Primary surgical therapy had to be delayed because of suspected bronchial carcinoma and additional diagnostics. After neoadjuvant therapy to downsize the tumor thrombus and exclusion of any additional malignant tumors, operation was done via abdominal access; no sternotomy was necessary. Results: Histopathological examinations of the primary tumor after tyrosine kinase inhibitor therapy were evaluated and compared to tumor biopsy material taken before therapy. Conclusion: Neoadjuvant therapy with Sutent® may represent a favorable treatment option in cases of locally advanced clear-cell RCC with extended tumor thrombus.
Topographical Sensitivity and Specificity of Endorectal Coil Magnetic Resonance Imaging for Prostate Cancer Detection
Authors: Colleselli Daniela , Schilling David , Lichy Matthias P. , Hennenlotter Jörg , Vogel Ulrich H. , Krueger Stephan A. , Kuehs Ursula , Schlemmer Heinz-Peter , Stenzl Arnulf , Schwentner Christian
Published: May 2010

Objectives: Endorectal coil magnetic resonance imaging (EC-MRI) is useful to evaluate prostate cancer localization. Herein, we evaluate sensitivity and specificity of EC-MRI in different regions of the prostate by comparing the acquired images to whole-mount sections of the prostate after radical prostatectomy. Methods: 69 patients with localized prostate cancer were included. After virtually dividing the prostate into 12 sectors, results of EC-MRI were compared to corresponding whole-mount sections by contingency analysis. Sensitivity and specificity were calculated for each of the 12 areas as well as for the dorsal and ventral region. Results: Sensitivity right/left was dorsal apex/mid/base 41/41, 60/67 and 73/79%; ventral 33/52, 43/42 and 47/52%. Specificity right/left was dorsal apex/mid/base 92/89, 82/75 and 88/69%; ventral 100/100, 100/92 and 88/83%. Local sensitivity and specificity regarding dorsal versus ventral was 88/100 and 65/87%. Conclusions: Local sensitivity decreased from basodorsal to apicoventral direction, whereas local specificity increased in the same direction. Therefore, prostate cancers demonstrated by MRI are more prone to be detected in the basodorsal region, whereas less false-positive results are found in the apicoventral region. These variations in topographical specificity and sensitivity need to be considered before radical prostatectomy or MRI-guided biopsy.
Protein Microarrays for Cancer Diagnostics and Therapy
Authors: Lin Jimmy Cheng-Ho
Published: May 2010

In this postgenomic age, cancer will be understood in intricate detail beyond the genomic level. New technologies are emerging that allow global proteomic level characterization, profiling and understanding. One of the most exciting emerging technologies of cancer proteomics is protein microarray. In this review, the different types of protein microarrays are discussed, including the methods, challenges and techniques of each type. Subsequently, the application of these specific methods to cancer diagnosis, prognosis and therapy will be overviewed, providing a general review of current methods, and proposing how protein arrays will help shape the future of oncoproteomics.
In vivo Analgesic Effect of Aqueous Extract of Tamarindus indica L. Fruits
Authors: Khalid S. , Shaik Mossadeq W.M. , Israf D.A. , Hashim P. , Rejab S. , Shaberi A.M. , Mohamad A.S. , Zakaria Z.A. , Sulaiman M.R.
Published: May 2010

Objective: To study the effects of Tamarindus indica L. aqueous fruit extract on the antinociceptive activities in rodent models. Methods: The analgesic effect was evaluated using acetic acid-induced writhing, hot plate and formalin tests. Results: The extract (60–600 mg/kg) significantly (p < 0.05) inhibited the writhing test in a dose-dependent manner with the percentage of analgesia recorded between 51.8 and 74.1%. In addition, the extract also significantly (p < 0.05) increased the latency time in the hot plate test in a dose-dependent manner. Further study showed that the extract elicited inhibitory activity in both the early and late phases of the formalin test. Moreover, pretreatment with 5 mg/kg naloxone, a nonselective opioid receptor antagonist, significantly (p < 0.05) modified the antinociceptive effect of the extract in all tests. Conclusion: The aqueous extract of T. indica possesses potential antinociceptive activity at both the peripheral and central levels, which are mediated via activation of the opioidergic mechanism.
Age- and Gender-Specific Smoothed Waist Circumference Percentiles for Kuwaiti Adolescents
Authors: Jackson Robert T. , Al-Hamad Nawal , Prakash Prasanna , Al-Somaie Mona
Published: May 2010

Objective: To ascertain abdominal obesity prevalence (waist circumference, WC) in adolescents and to develop smoothed WC percentile charts for Kuwaiti adolescents for public health use. Subjects and Methods: A cross-sectional study of 4,219 healthy Kuwaiti male and female secondary school students between the ages of 11–19 years was examined. Adolescents were drawn from all geographical regions of the country, as part of the Kuwait Nutrition Surveillance Program (KNSP). The KNSP consists of yearly data collections of variables, including weights, heights, and WCs and several sociodemographic variables. LMS regression was used to develop smoothed WC percentile curves. The final percentile curves presented are the result of smoothing three age-specific curves, termed lambda (L), mu (M), and sigma (S) for each gender. Results: Between 5.9 and 12.8% of females and 8.0–30.3% males had WC values ≧90th percentile. Moreover, the mean WC of males was consistently higher than those of females at each age and the percent of adolescents who exceed the 90th percentile increased with age in males, but not in females. Conclusion: Mean WC was higher in males than in females at every age. In most cases, two to three times greater percentages of males, compared to females, equaled or exceeded the 90th percentile, a value frequently associated with higher cardiovascular risk. These results indicate the urgent need to reduce abdominal obesity, an important indicator of the metabolic syndrome, in Kuwaiti adolescents.
Anti-Acne-Inducing Bacterial Activity of Mangosteen Fruit Rind Extracts
Authors: Pothitirat Werayut , Chomnawang Mullika Traidej , Gritsanapan Wandee
Published: May 2010

Objective: The aims of this study were to determine the most effective solvent extract of mangosteen, anti-acne- inducing bacterial activity and the amount of α-mangostin, a major active component in each mangosteen fruit rind extract, using high-performance liquid chromatography (HPLC). Materials and Methods: The fruit rinds of mangosteen were extracted with hexane, dichloromethane, ethanol and water. The extracts were tested for antibacterial activity against bacteria that induce acne, including Propionibacterium acnes and Staphylococcus epidermidis. Thin-layer chromatographic autobiography against these bacteria was also performed for each extract, while the α-mangostin content was analyzed using a validated HPLC method. Results: The dichloromethane extract exhibited the strongest antibacterial effect with minimum inhibitory concentration values for both bacterial species at 3.91 µg/ml, while the minimum bactericidal concentration values against P. acnes and S. epidermidis were 3.91 and 15.63 µg/ml, respectively. Thin-layer chromatographic autobiography indicated that α-mangostin was present in all extracts, except the water extract, and is a major active component against both P. acnes and S. epidermidis. Using HPLC, the dichloromethane extract yielded the highest content (46.21% w/w) of α-mangostin followed by the ethanol extract (18.03% w/w), the hexane extract (17.21% w/w) and the water extract (0.54% w/w). Conclusions: Dichloromethane extract exhibited the strongest anti-acne-inducing bacterial effect and this extract yielded the highest amount of α-mangostin.
Antiinflammatory and Antinociceptive Activities of Zingiber zerumbet Methanol Extract in Experimental Model Systems
Authors: Zakaria Z.A. , Mohamad A.S. , Chear C.T. , Wong Y.Y. , Israf D.A. , Sulaiman M.R.
Published: May 2010

Objective: The present study was carried out to determine the antiinflammatory and antinociceptive activities of a methanol extract of Zingiber zerumbet rhizomes (MEZZ) using various experimental model systems. Materials and Methods: The MEZZ was prepared by macerating oven-dried (50°C) powdered rhizomes (1.2 kg) of Z. zerumbet in 80% methanol in a ratio of 1:20 (w/v) for 48 h. The supernatant was collected, filtered and evaporated to dryness under reduced pressure (50°C) yielding approximately 21.0 g of the crude dried extract. The crude dried extract was stored at –20°C prior to use and was dissolved in normal saline (0.9% NaCl) immediately before administration at concentrations required to produce doses of 25, 50 and 100 mg/kg. Results: All dosages of MEZZ showed significant (p < 0.05) antiedema activity when assessed using the carrageenan-induced paw edema test and the cotton-pellet-induced granuloma test. The MEZZ exhibited significant (p < 0.05) antinociceptive activity when assessed by the writhing, hot plate and formalin tests. Pretreatment with naloxone (5 mg/kg) significantly decreased the latency of discomfort produced by the 100 mg/kg dose of MEZZ in the hot plate test. Conclusion: MEZZ produced antiinflammatory and antinociceptive activities which may involve the inhibition of bradykinin-, prostaglandin-, histamine- and opioid-mediated processes.
Impact of a Continuing Education Program on Pharmacists’ Knowledge and Attitudes toward Asthma Patient Care
Authors: Chiang Yi-Chun , Lee Chun-Nin , Lin You-Mei , Yen Yu-Hsuan , Chen Hsiang-Yin
Published: May 2010

Objective: The objective of this study was to evaluate the impact of an asthma continuing education program on pharmacists’ knowledge and attitudes related to asthma pharmaceutical care. Subjects and Methods: A 20-hour continuing education program was conducted by the joint efforts of the Taipei City Government, Taiwan Association of Asthma Education and Taipei Medical University Wan Fang Hospital, in a series of 4 days afternoon sessions from June 26 to July 4, 2004. One hundred and twenty-five pharmacists participated. The Asthma Knowledge Test in Mandarin and the Asthma Attitude Scale in Mandarin were developed by adapting the scale used to evaluate the impact of pharmacist continuing education programs on diabetic care. The results before and after the intervention were compared to evaluate the impact of the program. Results: Of the 125 participants, 105 returned both the pre- and post-intervention questionnaires, for a response rate of 84.0%. The total score of the attitude section increased significantly from 40.04 ± 3.35 to 42.54 ± 2.98 (full score = 50, p < 0.001). The total score of the knowledge section also increased significantly from 7.18 ± 1.31 to 7.56 ± 1.15 (p = 0.008). Improvement in the attitude score was found in 70 (67.0%) subjects, and in the knowledge score in 45 (43.5%) subjects. Conclusion: The study demonstrated that attitude and knowledge toward asthma care improved after the continuing education program. Further study of long-term impact and direct changes in asthma pharmaceutical care practice will be necessary.
A Survey of Knowledge of Sexually Transmitted Infections among Patients at a Public Hospital in Pulau Pinang, Malaysia
Authors: Anwar Mudassir , Sulaiman Syed A. Syed , Khan Tahir M.
Published: May 2010

Objective: The aim of this study was to assess the patients’ knowledge and awareness of sexually transmitted infections (STIs). Subjects and Methods: A face-to-face interview was conducted among the patients visiting the Venereal Diseases Outpatient Department of the General Hospital of Pulau Pinang (Malaysia). A 19-item questionnaire was used. A total of 116 patients participated in the study and 107 patients had valid responses. The reliability and internal consistency of the questionnaire tool was estimated on the basis of Cronbach’s alpha (= 0.81). The Statistical Package for Social Sciences (SPSS 13.0®) was used for data analysis. Student’s t test and analysis of variance were used to analyse the knowledge differences among the groups. Results: Of the 107 patients, 82 (76.6%) were diagnosed with syphilis; AIDS was the most commonly known STI among the patients. Of the 107 patients, 35 were sexually active and of these 23 (65.7%) had more than 1 sexual partner. The most popular source of knowledge was newspapers (51 patients, 47.7%), with hospitals (3 patients, 2.8%) being the least popular one. Overall mean score on knowledge questions was 12.21 out of the maximum of 33 points. Knowledge about causative organisms, risk groups, transmission, symptoms, prevention and treatment of STIs was inadequate. The knowledge level was significantly related to gender (p = 0.03), religion (p = 0.005), educational level (p = 0.000), marital status (p = 0.000) and income level (p = 0.036). Conclusion: This study demonstrated evidence of poor knowledge of STIs amongst the patients attending an STI service in the General Hospital of Pulau Pinang (Malaysia). Hence there is an immediate need for efforts towards improving patient knowledge of STIs.
Relation of New and Old Formulas for Estimating Creatinine Clearance among Stroke Survivors
Authors: Ovbiagele Bruce
Published: May 2010

Objective: To assess whether the newly proposed formula for estimating glomerular filtration function (GFR) – the Chronic Kidney Disease Epidemiology (CKD-EPI) equation – would be materially distinct from the established Modification of Diet in Renal Disease (MDRD) equation in diagnosing chronic kidney disease (CKD) among US stroke survivors. Materials and Methods: Data from the National Health and Nutrition Examination Survey from 1999–2004, a nationally representative sample of adults from the United States, were used to assess the correlation between the MDRD and CKD-EPI equations among persons aged ≧55 years who had experienced a prior stroke. CKD was defined as GFR <60 ml/min/1.73 m2. Results: Among 6,382 adults, 5,321 (83%) had full and complete data. With MDRD, 20.4% of the sample had CKD vs. 19.4% using the CKD-EPI. There was 97.7% agreement between MDRD and CKD-EPI using the 60 ml/min/ 1.73 m2 cutoff point. The correlation between both equations was extremely high (r = 0.954). Conclusion: The newly developed CKD-EPI equation is very highly correlated to the more established MDRD formula and does not materially change CKD diagnosis made by the latter among persons with a history of stroke.
Classic Galactosemia Presenting with Unilateral Peters’ Anomaly
Authors: Faras Hadeel , Al-Raqum Fayka , Ramadan Dina
Published: May 2010

Objective: To report a case of classic galactosemia that presented with a rare ocular finding, Peters’ anomaly. Clinical Presentation and Intervention: A neonate, born to first-degree healthy cousins, presented with persistent vomiting, failure to thrive, lethargy, and jaundice. Corneal opacity was noticed in the left eye. Hydration and empiric antibiotics were started after collection of the required blood work, which included both a septic and a metabolic workup. A deficiency in erythrocyte galactose-1-phosphate uridyltransferase was found, and this led to the diagnosis of classic galactosemia and the elimination of galactose from the diet. Furthermore, a diagnosis of left unilateral Peters’ anomaly was made after examination by a pediatric ophthalmologist. The patient was discharged in stable condition and follow-up visits were scheduled with the metabolic clinic, a dietician, and the pediatric ophthalmologist. Conclusion: This was a case of classic galactosemia presenting with Peters’ anomaly, probably due to autosomal recessive disorder from first-degree consanguinity marriage.
Two Cases of Walker-Warburg Syndrome Complicated by Hydrocephalus
Authors: Preuss M. , Heckmann M. , Stein M. , Nestler U.
Published: May 2010

Walker-Warburg syndrome is a very rare autosomal recessive disorder with congenital muscular dystrophy, brain malformations on the basis of a neuronal migration defect and ocular abnormalities. We report our experience in treating two cases of Walker-Warburg syndrome complicated by hydrocephalus with shunting and endoscopic techniques.
Infratorcular Meningoencephalocele with Dermoid Cyst
Authors: Mahore Amit , Fonseca Alejandro , Dange Nitin , Redhu Rakesh , Muzumdar Dattatreya , Goel Atul
Published: May 2010

Encephalocele represents one end of the spectrum of open neural tube defects. We report an infant with Chiari type 3 malformation manifesting as infratorcular occipital meningoencephalocele with dermoid cyst. To our knowledge, this is the first time that this association is described. The pathogenesis, surgical treatment, prognosis and management difficulties are also being discussed.
Isolated Cerebrospinal Fluid Leakage due to a Spinal Stab Wound in a Child
Authors: Kim Ji Hye , Kang Jin-Ah , Kim Jun Sig , Han Seung Baik
Published: May 2010

Spinal stab wounds are relatively rare, especially in children. Moreover, as the pediatric spine anatomy differs from that of an adult, physicians managing stab wounds in this area should keep some special considerations in mind. This study reports an interesting case of spinal cerebrospinal fluid leakage without significant spinal injury in a 32-month-old child.
Central Pontine Myelinolysis in a Pediatric Head Injury Patient
Authors: Singh Deepak Kumar , Rastogi Manu , Husain Mazhar
Published: May 2010

Central pontine myelinolysis occurs inconsistently as a complication of severe and prolonged hyponatremia, particularly when corrected too rapidly. It is a concentrated, frequently symmetric, noninflammatory demyelination within the central basis pontis. We describe a head injury patient who suffered this clinical entity as a consequence of rapidly corrected hyponatremia. Clinical manifestation and radiological findings are described along with a review of the pertinent literature.
Morphological and Extracellular Matrix Changes following Vocal Fold Injury in Mice
Authors: Yamashita Masaru , Bless Diane M. , Welham Nathan V.
Published: May 2010

Mouse experimental models are commonly utilized tools in biomedical research but remain underrepresented in vocal fold biology, presumably due to the small size of the larynx and limited description of the anatomical, cellular and extracellular composition of the vocal folds. In this study, we provide a whole-mount serial section-based histological description of vocal fold morphology of wild-type FVB strain mice, alongside a histological and immunohistochemical (IHC)-based quantitative analysis of extracellular matrix (ECM) alteration 1, 7, 14, 28, 42 and 56 days following unilateral vocal fold injury. IHC was specific for procollagen type I, collagen type I, collagen type III, collagen type IV, elastin, decorin, fibronectin and hyaluronic acid binding protein 2. The histological description confirmed the presence of a laryngeal alar structural complex in the mouse, which appears to be a morphological feature unique to rodents. The lamina propria appeared uniform without evidence of a distinct layer structure as has been reported in larger animals and humans. Time-dependent alterations in vocal fold morphology, ECM organization and ECM protein/glycoconjugate abundance were observed in injured vocal folds compared to control. The presence of a mature scar was observed between 28 and 42 days postinjury. Morphological and ECM changes following vocal fold injury in the mouse were generally consistent with those reported in other animal models, particularly the rat, although wound repair in the mouse appears to occur at a faster rate.
Subsets of GABA Neurons in the Human Cerebellum in Normal Controls and Senile Dementia of the Alzheimer Type Patients Detected by Glutamate Decarboxylase, GABAA/Benzodiazepine Receptor Protein, Calbindin D-28k and Parvalbumin Immunocytochemistry (Part 2 of 2)
Authors: Zetzsche Thomas , Baimbridge Kenneth G. , Möhler Hanns , Chan-Palay Victoria
Published: May 2010

The distribution of gamma-aminobutyric acid (GABA)-ergic neurons in the postmortem human cerebellar cortex and dentate nucleus was studied using antibodies against glutamate decarboxylase (GAD) and two different cytoplasmic calcium-binding proteins, parvalbumin and calbindin D-28k (CaBP), and the alpha-subunit of the GABAA/benzodiazepine receptor protein. The cerebellum of normal controls was compared to those of patients with senile dementia of the Alzheimer type (SDAT) in order to determine the involvement of these neurons in the dementing disorder. In the normal human cerebellar cortex all neuronal types except granule cells were GAD-labeled. Immunoreactivity was found predominantly in axonal structures, particularly in basket plexus around Purkinje cell somata. Antibodies against CaBP specifically stained all Purkinje cells in their entirety including axons and dendritic spines. Parvalbumin immunoreactivity was found in a subpopulation of Purkinje cells, basket and stellate cells but not in Golgi and granule cells. Parvalbumin-immunoreactive basket plexuses were found around Purkinje cell somata. The most intense labeling with the GABAA/benzodiazepine receptor antibody was found on the surface of granule cells. Purkinje, basket and stellate cells showed only a weak labeling of their surface. In the dentate nucleus only small neurons showed GAD immunoreactivity. Large neurons were densely covered with labeled axons and varicosities. No cell somata were stained with antibodies against CaBP and parvalbumin. All types of large and small dentate neurons showed immunoreactivity against GABAA/benzodiazepine receptor protein on the surface of their soma and dendrites. SDAT is accompanied by some changes in neurons belonging to the GABA subset. Fewer spines were found on the dendrites of Purkinje cells and on large dentate neurons. In the granular layer, more Purkinje axonal deformations ('torpedoes') and a hypertrophic network of Purkinje axon collaterals were found.
Potential Applications for Monoamine Oxidase B Inhibitors. pp 342–348
Authors: Kabins Darryl , Gershon Samuel
Published: May 2010

Monoamine oxidase inhibitors (MAOIs) are not only effective antidepressants, but also have several other applications. Yet, they are infrequently used as a result of their potential to cause toxic side effects such as tyramine-induced hypertensive crisis (cheese effect). A resurgence of interest in MAOIs followed the finding of two forms of MAO. This resulted from the development of drugs that selectively inhibit the metabolism of serotonin and norepinephrine (MAO-A) or dopamine and phenethylamine (MAO-B). MAO-B is the predominant MAO found in the human brain. Theoretically, selective MAO-B inhibition can enhance brain MAO levels while leaving intestinal MAO-A intact, thus bypassing the cheese effect, L-deprenyl is the most extensively studied MAO-B inhibitor. At low doses, it is very selective for MAO-B and is not associated with the cheese effect. At higher doses, it is virtually nonselective. L-deprenyl enhances the effect of L-dopa on Parkinson's disease and may retard its natural progression. Although studies have found L-deprenyl to be an effective antidepressant only at nonselective doses, certain subtypes of depression may respond to selective doses. Also, evidence suggests that L-deprenyl has a positive effect on the general function and cognitive abilities of Alzheimer patients. Studies to date, including those showing a significant increase in the life span of rats following L-deprenyl use have led to the speculation that L-deprenyl may not only treat or retard degenerative diseases and acute brain insults, but may prove to be the first antiaging medication. Several other potential applications of MAO-B inhibitors include panic, ADHD, sexual dysfunction, and PTSD. It remains unclear what role MAO-B inhibition plays in the various therapeutic effects of L-deprenyl. Other potential mechanisms are discussed.
Parvalbumin Neurons in the Hippocampus in Senile Dementia of the Alzheimer Type, Parkinson's Disease and Multi-Infarct Dementia (Part 2 of 2)
Authors: Chan-Palay V.C. , Zetzsche T. , Höchli M.
Published: May 2010

The immunogold-silver-staining method (IGSS) was used for the detection of hippocampal neurons containing the cytoplasmic calcium-binding protein parvalbumin in senile dementia of the Alzheimer type (SDAT), Parkinson's disease and multi-infarct dementia (MID). Computer-based image analysis of cell numbers in the hippocampus proper and the entorhinal cortex, measurement of total dendritic length of selected neurons and quantitative microdensitometry of immunoreacted sections was performed. In severe SDAT cases a loss of parvalbumin-immunoreactive (parv-i) neurons and a reduction of dendritic fields was detected especially in CA1 and the subiculum. In the entorhinal cortex the general atrophy exceeded the decrease of parvalbumin immunoreactivity. Mild SDAT cases showed only minor alterations of parv-i neurons and in cases of parkinsonism without cognitive disorders or in those with depression parv-i neurons were not affected. However, in cases of parkinsonism with dementia and in MID a severe cell loss and a drastic reduction of dendritic arborization in the hippocampus proper was detected, which was accompanied by additional morphological alterations due to ischemic damage. We conclude that parv-i neuronal networks in the hippocampus are damaged in some patients with dementing disorders in SDAT, Parkinson's disease and MID consecutive to Alzheimer or ischemia related pathology.
Raphe Serotonin Neurons in the Human Brain Stem in Normal Controls and Patients with Senile Dementia of the Alzheimer Type and Parkinson's Disease: Relationship to Monoamine Oxidase Enzyme Localization (Part 2 of 3)
Authors: Chan-Palay V. , Höchli M. , Jentsch B. , Leonard B. , Zetzsche T.
Published: May 2010

The raphe serotonin system was studied in patients with senile dementia of the Alzheimer type (SDAT) or with Parkinson's disease and compared with normal controls. Postmortem brain stems were cut in coronal sections from the red nucleus to the decussation of the pyramidal tract and were reacted with PH8 antibodies (PH8) which cross-react with tryptophan hydroxylase, the synthesizing enzyme for serotonin. In addition, adjacent sections were reacted with antibodies against tyrosine hydroxylase (TH) to detect catecholamine neurons in the locus ceruleus (LC), with monoamine oxidase (MAO) A antibodies, which labeled most neurons in the LC, or with MAO B antibodies which labeled a subpopulation of neurons in the raphe nuclei. A computer-based-image-analysis system was used for counting cell numbers and, in addition, 3-dimensional reconstructions of all raphe nuclei were made with this program. In SDAT, a loss of PH8-immunoreactive (PH8-i) neurons was detected in the raphe nuclei. This loss was most pronounced in the ventrolateral division of the dorsal raphe nucleus and was correlated to the cortical pathology and age of the patients. In addition the number of TH-immunoreactive (TH-i) neurons was reduced in the LC, with the rostral parts of the nucleus being the most severely affected. A comparison of the morphological changes in SDAT revealed that, in the same cases, the greatest neuronal alterations were found in the TH-i neurons in the LC rather than in the PH8-i neurons in the raphe nuclei. This reduction of TH-i neurons was matched by a loss of MAO A-immunoreactive (MAO A-i) neurons in the LC in SDAT. Similarly, the loss of PH8-i neurons was accompanied by a loss of MAO B-immunoreactive neurons in the raphe nuclei. In Parkinson's disease two different types of pathologies were found in the raphe nuclei; in one case with dementia a reduction of PH8-i neurons was seen in the ventrolateral and caudal subnucleus of the dorsal raphe. In two other cases with depression, severe cell loss was found in the raphe obscurus. All these Parkinson cases showed a considerable reduction of TH-i and MAO A-i neurons in the LC. Thus, the catecholamine lesions of the LC are more severe than the serotonin lesions of the raphe in SDAT patients and this was true of Parkinson patients as well. The relationships of catecholamine neurons with the MAO A enzyme localization and of serotonin neurons with the MAO B enzyme were also confirmed.
Raphe Serotonin Neurons in the Human Brain Stem in Normal Controls and Patients with Senile Dementia of the Alzheimer Type and Parkinson's Disease: Relationship to Monoamine Oxidase Enzyme Localization (Part 3 of 3)
Authors: Chan-Palay V. , Höchli M. , Jentsch B. , Leonard B. , Zetzsche T.
Published: May 2010

The raphe serotonin system was studied in patients with senile dementia of the Alzheimer type (SDAT) or with Parkinson's disease and compared with normal controls. Postmortem brain stems were cut in coronal sections from the red nucleus to the decussation of the pyramidal tract and were reacted with PH8 antibodies (PH8) which cross-react with tryptophan hydroxylase, the synthesizing enzyme for serotonin. In addition, adjacent sections were reacted with antibodies against tyrosine hydroxylase (TH) to detect catecholamine neurons in the locus ceruleus (LC), with monoamine oxidase (MAO) A antibodies, which labeled most neurons in the LC, or with MAO B antibodies which labeled a subpopulation of neurons in the raphe nuclei. A computer-based-image-analysis system was used for counting cell numbers and, in addition, 3-dimensional reconstructions of all raphe nuclei were made with this program. In SDAT, a loss of PH8-immunoreactive (PH8-i) neurons was detected in the raphe nuclei. This loss was most pronounced in the ventrolateral division of the dorsal raphe nucleus and was correlated to the cortical pathology and age of the patients. In addition the number of TH-immunoreactive (TH-i) neurons was reduced in the LC, with the rostral parts of the nucleus being the most severely affected. A comparison of the morphological changes in SDAT revealed that, in the same cases, the greatest neuronal alterations were found in the TH-i neurons in the LC rather than in the PH8-i neurons in the raphe nuclei. This reduction of TH-i neurons was matched by a loss of MAO A-immunoreactive (MAO A-i) neurons in the LC in SDAT. Similarly, the loss of PH8-i neurons was accompanied by a loss of MAO B-immunoreactive neurons in the raphe nuclei. In Parkinson's disease two different types of pathologies were found in the raphe nuclei; in one case with dementia a reduction of PH8-i neurons was seen in the ventrolateral and caudal subnucleus of the dorsal raphe. In two other cases with depression, severe cell loss was found in the raphe obscurus. All these Parkinson cases showed a considerable reduction of TH-i and MAO A-i neurons in the LC. Thus, the catecholamine lesions of the LC are more severe than the serotonin lesions of the raphe in SDAT patients and this was true of Parkinson patients as well. The relationships of catecholamine neurons with the MAO A enzyme localization and of serotonin neurons with the MAO B enzyme were also confirmed.
MAO A and B Immunoreactivity in the Hippocampus, Temporal Cortex and Cerebellum of Normal Controls and of Patients with Senile Dementia of the Alzheimer Type (Part 2 of 2)
Authors: Zetzsche T. , Chan-Palay V.
Published: May 2010

The distribution of MAO A and B immunoreactivity was studied in the postmortem hippocampus, cerebellum and temporal cortex of normal controls and in patients with senile dementia of the Alzheimer type (SDAT). In normal control, neurons, glia cells, cellular processes and the walls of blood vessels were found to be MAO-immunoreactive (MAO-i). In the hippocampus of control cases, a subpopulation of small nonpyramidal neurons was MAO A-i. In addition, the somata of granule and pyramidal cells were densely surrounded by MAO B-i cellular processes. In the cerebellum, fine MAO A and B-i cellular processes and small varicosities were found in the cortex and in the dentate nucleus. In the normal temporal cortex, glia cells and cellular processes were MAO A-i and MAO B-i in all lamina. In SDAT, some changes of MAO immunoreactivity were encountered in all of the examined brain areas. The hippocampal MAO A-i neurons were well preserved in the dentate gyrus. However, large MAO B-i glia cells were found in the Ammon's horn, subiculum and entorhinal cortex, where they formed cell clusters or patches with increased MAO B immunoreactivity. Bodian-stained sections of the same hippocampi showed neuritic plaques in a similar number and regional distribution as the patches of increased MAO B immunoreactivity. In the cerebellar cortex of SDAT patients, plexuses of thick MAO A-i processes as well as patches of increased MAO B immunoreactivity with clusters of large MAO B-i glia cells were found. In the temporal cortex of SDAT cases, proliferation of large MAO B-i glia cells was detected. These glia cells formed numerous patches of increased MAO B immunoreactivity which were predominantly found in the upper cortical layers, similar to the distribution of neuritic plaques.
Senile Dementia of Lewy Body Type and Alzheimer Type Are Biochemically Distinct in Terms of Paired Helical Filaments and Hyperphosphorylated Tau Protein (Part 2 of 2)
Authors: Harrington C.R. , Perry R.H. , Perry E.K. , Hurt J. , McKeith I.G. , Roth M. , Wischik C.M.
Published: May 2010

We have used biochemical assays to examine cingulate and occipital cortices from age-matched cases of Alzheimer's disease (AD; n = 12), senile dementia of the Lewy body type (SDLT; n = 13), Parkinson's disease (PD; 5 non-demented cases and 7 cognitively impaired cases) and controls (n = 11) for paired helical filaments (PHFs), phosphorylated and normal tau protein and Β/A4-protein. Whereas cingulate cortex is characterised by relatively high densities of cortical Lewy bodies in the SDLT cases and lower numbers in PD, these inclusion bodies were absent in the cingulate cortex from AD and control cases. Protease-resistant PHFs and hyperphosphorylated tau protein were found in AD and, at low levels, in a minority of SDLT cases. Qualitatively, both of these preparations were indistinguishable in SDLT from those found in AD but levels of both parameters in SDLT were less than 5% of those in AD. SDLT, PD and control groups did not differ from each other in terms of the quantity of protease-resistant PHFs or the level of hyperphosphorylated tau. Furthermore, PHF accumulation did not distinguish between PD cases with or without dementia. The levels of normal tau protein did not differ between the four groups. Β/A4 protein levels did not distinguish between PD and control groups, between AD and SDLT groups, or between SDLT and control groups for either cingulate or occipital cortices. Thus extensive accumulation of PHFs in either neurofibrillary tangles or dystrophic neurites is not a feature of either SDLT or PD. Our findings provide molecular support for the neuropathological and clinical separation of SDLT as a form of dementia that is distinct from AD.
Visual Balloon-Guided Point-by-Point Ablation
Authors: Dukkipati Srinivas R. , Neuzil Petr , Skoda Jan , Petru Jan , d'Avila Andre , Doshi Shephal K. , Reddy Vivek Y.
Published: May 2010

Background—

While conceptually straightforward, placing point-to-point contiguous radiofrequency lesions to achieve pulmonary vein isolation (PVI) is technically challenging in patients with paroxysmal atrial fibrillation. Furthermore, chronic efficacy is limited by late PV reconnections. A novel compliant balloon ablation catheter able to deliver visually guided short arcs/spots of laser energy was tested in initial preclinical and clinical cases to determine if visual guidance could predict reliable and persistent PVI.

Methods and Results—

This study consisted of (1) an experimental porcine phase with both acute (n=15 pigs) and 4-week chronic (n=10) data and (2) a single-center clinical feasibility phase (n=27 patients with paroxysmal atrial fibrillation), again with acute and 3-month chronic data. Under endoscopic guidance, point-by-point perivenous ablation was performed in a contiguous and overlapping manner. Each porcine PV was longitudinally sectioned for detailed histological analysis. At 3 months after ablation, patients underwent a prespecified remapping procedure regardless of symptomotology. In the acute and chronic animals, 29 of 30 (97%) PVs were electrically isolated after placing the initial circumferential lesion set. For the 4-week chronic animals, 80% of PVs remained isolated; lesions were histologically circumferential in 120 of 120 (100%) PV sections and transmural in 116 of 120 (96.7%) PV sections (average transmurality=99.0±5.5%). In patients, 100% of the PVs were isolated after 1.3 attempts per PV—84% of them (85 of 101) isolated after the initial visually guided lesion set. At 3 months, 61 of 68 (90%) PVs continued to be electrically isolated.

Conclusions—

Using a visually guided, compliant balloon ablation catheter with point-by-point ablative capability, PV isolation can be achieved in a reliable, reproducible, and persistent manner.
Control of Macrophage Activation and Function by PPARs
Authors: Chawla Ajay
Published: May 2010

Abstract
:

Macrophages, a key component of the innate defense against pathogens, participate in the initiation and resolution of inflammation, and in the maintenance of tissues. These diverse and at times antithetical functions of macrophages are executed via distinct activation states, ranging from classical to alternative to deactivation. Because the dysregulation of macrophage activation is pathogenically linked to various metabolic, inflammatory and immune disorders, regulatory proteins controlling macrophage activation have emerged as important new therapeutic targets. Here, the mechanisms by which peroxisome proliferator-activated receptors (PPARs) transcriptionally regulate macrophage activation in health and disease states, including obesity, insulin resistance and cardiovascular disease, are reviewed.
Shorter Telomere Length is Associated With Greater Decrease in Ankle-Brachial Index in Elderly Chinese Women but not Men
Authors: Woo Jean , Tang Nelson L. S. , Suen Eddie , Leung Jason
Published: May 2010

Telomere shortening has been shown to contribute to the pathogenesis of atherosclerosis directly or through influencing cardiovascular risk factors. We examined telomere length (TL) and change in ankle-brachial index (ABI) over 5 years in a Chinese population aged 65 years and older living in the community. Telomere length was determined using the quantitative polymerase chain reaction (PCR) method in 976 men and 1030 women. Ankle-brachial index was measured using Doppler ultrasound. Analysis of covariance was used to examine the relationship between quartiles of TL and baseline ABI values as well as percentage change in ABI, adjusting for confounders. Women had longer TL and lower ABI values compared with men, and there was a significant trend for an inverse association between TL and percentage decline in ABI after adjustment for confounders. No significant association was observed in men. The findings support the association between TL and markers of atherosclerosis in older women but not men.
Life-course Determinants of Need for Dental Prostheses at Age 24
Authors: Correa M.B. , Peres M.A. , Peres K.G. , Horta B.L. , Gigante D.P. , Demarco F.F.
Published: May 2010

This study aimed to assess the prevalence of use and need for dental prostheses (UNDP) by individuals at age 24 and their life-course determinants. A representative sample (n = 720) of all 5914 births occurring in Pelotas in 1982 were prospectively investigated, and the UNDP were assessed in 2006. Exploratory variables included demographic and socio-economic, oral health, and dental service utilization patterns during the life-course. The prevalence of UNDP was 2.1% and 29.7%, respectively. Multivariable Poisson regression analysis showed that low socio-economic status through the life-course [Prevalence Ratio (PR) = 1.56 (95% CI: 1.08-2.26)], lower maternal schooling in childhood [PR 2.79 (1.34-5.79)], no oral hygiene instruction by a dentist at age 15 [PR 1.64 (1.11-2.41)], and caries presence at age 15 (high DMFT tertile) [PR 2.90 (1.98-4.24)] were associated with prosthetic treatment needs. These results support the hypothesis that life-course socio-economic, behavioral, and clinical determinants are associated with the need for dental prostheses.
Genetic and Environmental Factors in Oral Health among Twins
Authors: Rintakoski K. , Kaprio J. , Murtomaa H.
Published: May 2010

To date, studies on the contributions of genetic factors to oral health have been inconclusive. We hypothesized that major dental diseases show a significant genetic component. The study was based on self-reported oral health among young adult twins. The data were derived from the fourth wave of the longitudinal FinnTwin16 study, in which participants completed a questionnaire in 2000-2002 enquiring about the number of filled teeth and the prevalence of gingival bleeding. We used quantitative genetic modeling, based on the genetic similarity of identical and non-identical twins, to calculate the most probable model for both filled teeth and gingival bleeding. The models revealed a strong genetic component behind the number of filled teeth, differing between males (49%) and females (68%), and a weaker genetic component affecting gingival bleeding, being similar for males and females (32%). Genetic factors contribute to inter-individual differences in oral health among young adults.
Biodegradation of Resin-Dentin Interfaces Increases Bacterial Microleakage
Authors: Kermanshahi S. , Santerre J.P. , Cvitkovitch D.G. , Finer Y.
Published: May 2010

Bis-GMA-containing resin composites and adhesives undergo biodegradation by human-saliva-derived esterases, yielding Bis-hydroxy-propoxy-phenyl-propane (Bis-HPPP). The hypothesis of this study is that the exposure of dental restorations to saliva-like esterase activities accelerates marginal bacterial microleakage. Resin composites (Scotchbond, Z250, 3M) bonded to human dentin were incubated in either buffer or dual-esterase media (pseudocholinesterase/cholesterol-esterase; PCE+CE), with activity levels simulating those of human saliva, for up to 90 days. Incubation solutions were analyzed for Bis-HPPP by high-performance liquid chromatography. Post-incubation, specimens were suspended in a chemostat-based biofilm fermentor cultivating Streptococcus mutans NG8, a primary species associated with dental caries, for 7 days. Bacterial microleakage was assessed by confocal laser scanning microscopy. Bis-HPPP production and depth and spatial volume of bacterial cell penetration within the interface increased with incubation time and were higher for 30- and 90-day PCE+CE vs. buffer-incubated groups, suggesting that biodegradation can contribute to the formation of recurrent decay.
Improvements in estimating a fatal accidents model formed by an Artificial Neural Network
Authors: Cansiz Omer Faruk
Published: May 2010

The Smeed Equation (SE) is the first model being used to improve the estimation of the number of dead in accidents that consist of the independent variables of population and number of vehicles and the dependent variable of the number of dead. In this study, the population variable in the SE is replaced with the number of drivers. At first, the SE is made suitable for USA data and the Revised SE is obtained. Then the coefficients are calculated again by the replacement of the number of drivers with population and the Improved SE is obtained. Afterwards, Artificial Neural Network (ANN) models are formed in both variable groups of population and number of drivers. The best ANN model, whose inputs are the number of vehicles and drivers, has 19 neurons, a tan-sig transfer function and a Levenberg—Marquardt training algorithm. In the comparison of ANN models and SE models, the value of R2 increases from 0.8906 to 0.9695 and the value of mean square errors (MSEs) decreases from 87,503 to 39,310. As a result the replacement of the number of drivers variable with population has a contribution in the estimation of the number of dead in vehicle accidents. This study showed that use of the number of drivers instead of the population in the number of dead prediction can be improved with the accuracy of the proposed models. Moreover, ANN models can be used to predict the number of dead in traffic accidents with a high correlation coefficient and a low MSE according to the SE and loglinear regression methods.