[Part VI. Antiparasitic Treatment for Chagas Disease]

Revista Chilena De Infectología : órgano Oficial De La Sociedad Chilena De Infectología. Oct, 2008  |  Pubmed ID: 18949153

As expert consensus has been arisen about universal antiparasitic treatment for all patients infected with Trypanosoma cruzi, most important drugs licensed for Chagas disease treatment are reviewed: nifurtimox and benznidazol, their mechanisms of action, doses, treatment schedules, adverse effects and contraindications. Two other drugs used for Chagas disease treatment, for which a Chilean experience may be exhibited, are allopurinol and itraconazole. Indications for treatment of Chagas disease in immunocompetent patients and immunocompromised hosts are detailed. This chapter refers besides to the evaluation and monitoring of antiparasitic therapy in immunocompromised patients, the availability of drugs and includes various forms facsimiles suggested to perform clinical and laboratory follow up of patients that undergo treatment, indicating the prescribed drug, adverse effects and time of follow up.

Application of UV-spectrophotometric Methods for Estimation of Tenofovir Disoproxil Fumarate in Tablets

Pakistan Journal of Pharmaceutical Sciences. Jan, 2009  |  Pubmed ID: 19168416

Two new, simple and cost effective UV-spectrophotometric and first order derivative methods were developed for estimation of tenofovir disoproxil fumarate in bulk and tablets. Tenofovir disoproxil fumarate was estimated at 260 nm in 0.1N HCl. In first order derivative, it showed amplitude at 273 nm. In both the methods linearity was found to be in the range of 5-40 micro/ ml; for UV-spectrophotometric method (Y=0.02586 x +0.0083; r(2)=0.9999) and for first order derivative spectrophotometric method (Y=0.00132 x +0.00035; r(2)=0.9995), respectively. These methods were tested and validated for various parameters according to USP guidelines. The quantitation limits were found to be 1.546 and 1.986 micro/ ml, for both the methods. The proposed methods were successfully applied for the determination of tenofovir disoproxil fumarate in pharmaceutical formulations. The results demonstrated that the procedure is accurate, precise and reproducible (relative standard deviation <2%), while being simple, cheap and less time consuming and can be suitably applied for the estimation of tenofovir disoproxil fumarate in different dosage forms.

Aberrant Expression of Synaptophysin in Two Metastatic Alveolar Rhabdomyosarcomas. Pitfalls in Fine Needle Aspiration Cytology Diagnosis

Cytopathology : Official Journal of the British Society for Clinical Cytology. Jan, 2010  |  Pubmed ID: 20109164

Cell Communication and Tissue Engineering

Communicative & Integrative Biology. Jan, 2010  |  Pubmed ID: 20539784

Gap junction intercellular communication (GJIC) is ubiquitous in the majority of cells and is indispensable for proper development and function of most tissues. The loss of gap junction mediated cell to cell communication leads to compromised development in many tissues and organs, and also facilitates tumorigenesis and autonomous cell behavior in cancerous cells. Because cells embedded in an extracellular matrix constantly interact through gap junctions to coordinate normal tissue functions and homeostasis, our group hypothesized that increasing cell to cell communication, via genetically engineering cells to overexpress gap junction proteins, could improve cell signaling and increase differentiation in interior regions of engineered tissue equivalents. In a recent paper,1 we presented a platform to regenerate full 3D equivalents of engineered tissue, providing a strategy to overcome a barrier in regenerative medicine. These findings suggest that both targeted delivery and cell-based strategies can be used as treatments to enhance communication in 3D living tissue.2 In this addendum, we address the effects of extracellular calcium (Ca(2+) (e)) on intracellular calcium (Ca(2+) (i)), GJIC and osteogenic differentiation under conditions in which bone marrow stromal cells (BMSCs) also exhibit higher cell-to-cell communication. As a key secondary messenger in many biological processes, the levels of Ca(2+) (e) and Ca(2+) (i) play a role in cell differentiation and may be a tunable signal in tissue regeneration. Higher cell-to-cell communication was achieved by both genetically engineering cells to overexpress connexin 43 (Cx43) and by a high density cell seeding technique, denoted micromass seeding (MM). The results presented in this addendum show that the intensity and duration of a second messenger, like calcium, can be augmented in a platform that enables higher cell-to-cell communication. The ability to modulate calcium signaling, combined with our previous approaches to modulate GJIC, may have an impact on tissue regeneration and therapies for communication incompetent cells, such as those associated with heart disease and certain types of cancer.

Gesundes Kinzigtal Integrated Care: Improving Population Health by a Shared Health Gain Approach and a Shared Savings Contract

International Journal of Integrated Care. 2010  |  Pubmed ID: 20689772

INTRODUCTION: Integrated care solutions need supportive financial incentives. In this paper, we describe the financial architecture and operative details of the integrated pilot Gesundes Kinzigtal. DESCRIPTION OF INTEGRATED CARE CASE: Located in Southwest Germany, Gesundes Kinzigtal is one of the few population-based integrated care approaches in Germany, organising care across all health service sectors and indications. The system serving around half of the population of the region is run by a regional health management company (Gesundes Kinzigtal GmbH) in cooperation with the physicians' network in the region (MQNK), a German health care management company with a background in medical sociology and health economics (OptiMedis AG) and with two statutory health insurers (among them is the biggest health insurer in Southwest Germany: AOK Baden-Württemberg). DISCUSSION AND (PRELIMINARY) CONCLUSION: The shared savings contract between Gesundes Kinzigtal GmbH and the two health insurers, providing financial incentives for managers and health care providers to realize a substantial efficiency gain, could be an appropriate contractual base of Gesundes Kinzigtal's population health gain approach. This approach is based on the assumption that a more effective trans-sector organization of Germany's health care system and increased investments in well-designed preventive programmes will lead to a reduction in morbidity, and in particular to a reduced incidence and prevalence of chronic diseases. This, in turn, is to lead to a comparative reduction in health care cost. Although the comparative cost in the Kinzigtal region has been reduced from the onset of Gesundes Kinzigtal Integrated Care, only future research will have to demonstrate whether-and to what extent-cost reduction may be attributed to a real population health gain.

The Third National Health and Morbidity Survey: Prevalence of Obesity, and Abdominal Obesity Among the Malaysian Elderly Population

Asia-Pacific Journal of Public Health / Asia-Pacific Academic Consortium for Public Health. Sep, 2010  |  Pubmed ID: 20833669

Obesity is an emerging public health threat in the elderly population in developing countries. Hence, the Third National Health and Morbidity Survey has assessed 4746 individuals aged 60 years and older recruited through a household survey to determine the prevalence of adiposity using body mass index and waist circumference. The national's prevalence of overweight and obesity in men was 29.2% (95% confidence interval [CI] = 27.2-31.3) and 7.4% (95% CI = 6.4-8.6), respectively. However, the prevalence decreased with age. The figures in women were 30.3% (95% CI = 28.5-32.1) and 13.8% (95% CI = 12.5-15.2), respectively. The prevalence of abdominal obesity was 21.4% (95%CI = 20.2-22.6), with 7.7% (95% CI = 6.7-9.0) in men and 33.4% (95% CI = 31.4-35.3) in women. Predictors of adiposity include the following: Malay and Indian ethnicity, higher education level, higher household income, from urban area, and being married. In conclusion, adiposity affects about one third of the Malaysian elderly population, especially those of the younger age group, women, and those with higher socioeconomic status.

Automatic Quantification of Spinal Curvature in Scoliotic Radiograph Using Image Processing

Journal of Medical Systems. Jan, 2011  |  Pubmed ID: 21267773

Choosing the most suitable treatment for the scoliosis relies heavily on accurate and reproducible spinal curvature measurement from radiographs. Our objective is to reduce the variability in spinal curvature measurement by reducing the user intervention and bias. In order to determine the reliability of the spinal curvature measurement as it is in the clinical measurement of scoliosis a methodological survey has been carried out that concludes with inter and intra observer error variation. The proposed method list out horizontal inclination of all the vertebrae's in terms of slopes using active contour models and morphological operators. This facilitates the radiologist to decide end vertebrae and hence inter/intra observer variation is completely eliminated. Tables 1 and 2 shows the observer error variation between manual and proposed methods in terms of mean and standard deviation.

Facet Joints Arthrosis in Normal and Stenotic Lumbar Spines

Spine. Jan, 2011  |  Pubmed ID: 21270678

ABSTRACT: Study Design. A descriptive CT study of lumbar facet joint (FJ) arthrosis in general and spinal stenosis populations.Objective. To reveal the prevalence of FJ arthrosis in general and stenosis populations and to establish its relationship to age and gender.Summary of Background Data. FJ arthrosis is a common radiographic finding and has been suggested as a cause of low back and lower extremity pain. It is also considered a dominant player in the genesis of lumbar spinal stenosis. Although it is well accepted that FJ arthrosis is an age dependent phenomenon, controversies still exist as to its association with gender and its prevalence at different spine levels. Additionally, data on FJ arthrosis frequency in spinal stenosis population are missing.Methods. Two groups were studied. The first included 65 individuals with LSS (mean age 66 ± 10 years) and the second, 150 individuals (mean age 52 ± 19 years) without LSS related symptoms. Both left and right FJ arthrosis for each vertebral level (L3 to S1) were evaluated on CT images (Brilliance 64, Philips Medical System, Cleveland Ohio). Chi-Square, Linear-by-Linear Association and McNemar test were carried out to reveal the correlation between FJ arthrosis and demographic factors (age, gender) and prevalence at different lumbar levels in both stenosis and non-stenosis groups. Additionally, a 2-way ANOVA was used to determine the association between BMI and FJ arthrosis.Results. The rate of FJ arthrosis at L3-4 and L4-5 were significantly higher (P<0.001) in the stenotic group compared to the control. In the control group the prevalence of FJ arthrosis increases cephalo-caudally (L3-L4 = 16%, L4-L5 = 28%, L5-S1 = 55%), whereas in the stenotic group there is a sharp increase from L3-4 (27%) to L4-5 (58%), but not from L4-5 to L5-S1 (55%). No association between FJ arthrosis and gender was noted. Although, mean BMI was significantly smaller in the control group compared to the stenotic group, no association between BMI and facet arthrosis was found. In the general population the prevalence of FJ arthrosis at all three levels was greater for the right side; however, significant difference (P = 0.004) was obtained only for L3-4. In all joints studied, the prevalence of FJ arthrosis increases considerably from the young age cohort (18-39) to the old age cohort (>60). Nevertheless, 10% of the young individuals (18-39) have already manifested FJ arthrosis at L5-S1. No arthrosis at that age was observed at L3-4.Conclusion. FJ arthrosis is an age-dependent and BMI and gender-independent phenomenon. In the general population, the prevalence of FJ arthrosis increases cephalo-caudally with the highest frequency at L5-S1. In the stenotic group, the highest frequency was observed at the two caudal levels; L4-5 and L5-S1. The prevalence of FJ arthrosis was greater for the right side.

Platelet-derived Growth Factor Receptor Alpha is Associated with Oxidative Stress-induced Retinal Cell Death

Current Eye Research. Apr, 2011  |  Pubmed ID: 21405954

The purpose of this study was to investigate the role played by platelet-derived growth factor-α (PDGFRα) in oxidative stress-induced retinal cell death. A previous proteomic study from our laboratory showed that expression of PDGFRα is elevated considerably in the retinas of an animal model of glaucoma-the excitatory amino acid carrier (EAAC) 1-deficient (EAAC1-/-) mouse.

Is Laparoscopic Inguinal Hernia Repair More Effective Than Open Repair?

Journal of the College of Physicians and Surgeons--Pakistan : JCPSP. May, 2011  |  Pubmed ID: 21575538

To systematically review randomized controlled trials, (RCT) evidence comparing Lichtenstein to total extraperitoneal (TEP) hernia repair in terms of clinical and cost effectiveness. Study Design: Case series. Place and Duration of Study: The study was conducted at University of Abderdeen, U.K.

Anthropometric Profile, Vertical Jump and Throwing Velocity, in Female Elite Anthropometric Profile, Vertical Jump and Throwing Velocity, in Female Elite Handball Players by Playing Positions

Journal of Strength and Conditioning Research / National Strength & Conditioning Association. Oct, 2011  |  Pubmed ID: 21997459

Female handball is a sport which has seen an accelerated development over the last decade. While anthropometric and physical characteristics have been studied for male sports team, in female handball, studies are scarce. The aim of this study was twofold: firstly, to describe anthropometric characteristics, throwing velocity, hand grip and muscular power of the lower limbs in female handball players, and secondly, to identify possible differences in these parameters in terms of individual playing positions (center, back, wing, pivot and goalkeeper). A total of 130 Spanish female elite handball players participated in the study (25.74 ± 4.84 years; 14.92 ± 4.88 years of playing experience). Anthropometric assessment was performed by all subjects following the International Society for the Advancement of Kinanthropometry (ISAK) protocols. Furthermore, all subjects performed a vertical jump test (Squat Jump and Countermovement Jump). Hand grip and throwing velocity in several situations were also assessed. A one-way analysis of variance (ANOVA), and a Tukey post hoc test were used to study differences among individual playing positions. Wings were less heavy, shorter and showed less arm span, than goalkeepers, backs and pivots. (p≤0.001). Additionally pivots were heavier than centers. Backs and pivots exhibited higher muscular mass than wings. Total player's somatotype was mesomorphy-endomorphy (3.89 - 4.28 - 2.29).Centers showed higher throwing velocity levels than wings in 9 m throws from just behind the line, with a goalkeeper. Backs exhibited higher hand grip values than wings. Statistical differences have been established between wings and others specific playing positions, especially with pivot and backs. Coaches can use this information in order to select players for the different specific positions.

Two Maternal Origins of Chinese Domestic Goose

Poultry Science. Dec, 2011  |  Pubmed ID: 22080007

China is particularly rich in goose genetic resources. Systematic study of the genetic diversity and origin of Chinese domestic geese will provide an important scientific basis for the conservation and utilization of these resources and for human history. The 521-bp control region (D-loop) of mitochondrial DNA from 26 goose breeds and 6 Landaise geese were sequenced. The results showed that the average haplotype diversity and nucleotide diversity of Chinese domestic geese were 0.1384 and 0.00029, respectively. Shared haplotype analysis and systematic evolution analysis revealed that Chinese domestic geese had 2 maternal origins. The Yili goose breed originated from the Greylag goose (Anser anser), and the other 25 domestic goose breeds originated from the swan goose (Anser cygnoides). An interesting finding was that 1 Linxian white goose and 1 Wanxi white goose shared the same H4 haplotype with the Rhine goose and the Landaise goose, which originated from the Greylag goose (A. anser). Further research on this finding is planned.

Reimplantation with a Conventional Length Electrode Following Residual Hearing Loss in Four Hybrid Implant Recipients

Cochlear Implants International. Jun, 2011  |  Pubmed ID: 22333755

Hypothesis: Revision surgery using a newer-generation conventional length cochlear implant electrode will provide improved speech perception in patients that initially underwent hybrid electrode implantation and experienced post-operative loss of residual hearing and performance deterioration. CLINICAL PRESENTATION: We present four patients who experienced delayed post-operative hearing loss following implantation with the Nucleus Hybrid S8 device and underwent reimplantation with the Nucleus Freedom or Nucleus 5 device using the Contour Advance array. Pure-tone thresholds and speech perception data were retrospectively reviewed. INTERVENTION: Four subjects underwent reimplantation with the Nucleus Freedom or Nucleus 5 device after experiencing deteriorating performance related to delayed acoustic hearing loss. Comparison of pre-revision performance to the most recent post-revision performance demonstrated improved speech perception performance in all subjects following reimplantation. CONCLUSIONS: A small percent of patients will experience a significant loss of residual low-frequency hearing following hybrid implantation thereby becoming completely reliant on a shorter electrode for electrical stimulation. In the current series, reimplantation with a conventional length electrode provided improved speech perception performance in such patients. Revision surgery with a conventional length electrode should be considered in 'short electrode' recipients who experience performance deterioration following loss of residual hearing.

Tobacco Addiction and The Risk of Upper Aerodigestive Tract Cancer in A Multicenter Case-Control Study

Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology. Feb, 2012  |  Pubmed ID: 22337537

BACKGROUND: While previous studies on tobacco and alcohol and the risk of upper aerodigestive tract (UADT) cancers have clearly shown dose-response relations with the frequency and duration of tobacco and/or alcohol, studies on addiction to tobacco itself as a risk factor for UADT cancer have not been published, to our knowledge. The aim of this report is to assess whether smoking addiction is a risk factor for UADT SCC risk in the multicenter case-control study (ARCAGE) in Western Europe independent of tobacco smoking or alcohol drinking intensity or duration.METHODS: The analyses included 1,905 ever smoking UADT SCC cases (871 oral cavity/oropharynx, 814 hypopharynx/larynx, 127 esophagus, and 93 overlapping oral cavity/pharynx) and 1,489 ever smoking controls. The addiction variables included first cigarette after waking up, difficulty refraining from smoking in places where it is forbidden, and cigarettes per day. Odds ratios (OR) and 95% confidence intervals (95% CI) for UADT cancers with addiction variables were estimated with unconditional logistic regression, adjusting for center, age, sex, education level, alcohol consumption, and tobacco smoking.RESULTS: Among current smokers, 76.47% of cases were categorized in the highest addiction level, whereas 54.69% of controls were in that category. The participants who smoked their first cigarette within 5 minutes of waking up were two times more likely to develop UADT SCC (OR = 2.22, 95% CI 1.57-3.15) than those who smoked 60 minutes after waking up. A higher modified Fagerstram score, reflecting greater tobacco addiction, was associated with an increased risk of UADT SCC among current smokers, but not among former smokers.CONCLUSION: We observed that time to first cigarette after waking up was associated with UADT SCC risk, regardless of heavy smoking or alcohol drinking behaviors. These results are consistent with residual effect of smoking that was not captured by the questionnaire responses alone. Cancer Epidemiol Biomarkers Prev; 21(3); 1-9. ©2012 AACR.

Research Addressing Follow-Up for Abnormal Cancer Screening Tests: NCI Portfolio Analyses

Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology. Feb, 2012  |  Pubmed ID: 22337540

PURPOSE: The study's purposes were to identify the portfolio of grants awarded by the National Cancer Institute that addressed follow-up to abnormal screening tests for colon, breast and cervical cancer, document key research design characteristics, and discuss questions and issues for future practice and research.METHODS: A standardized form was used to audit grants funded from 2002 through 2011. Grant text was independently reviewed by two auditors; differences in reports were discussed until consensus was reached. The investigators then summarized findings in order to distill trends and issues.RESULTS: Twelve grants met inclusion criteria; 5, 4, 2 and 1 addressed follow-up of Pap tests, mammography, and colorectal tests and multiple screens respectively. Fifty percent were R01 awards, the majority of which applied group or individual RCT designs. One was a prospective cohort study. R21s typically emphasized qualitative methods and stressed behavioral epidemiology, measurement tool development and intervention planning; several listed aims related to determining prevalence. Definition of outcome measures was variable: e.g. completion of a follow-up test; time to follow-up; and steps until diagnosis. Four studies explicitly focused on ethnic/racial disparities; 5 on low income and underserved populations. Several emphasized measurement development. Three included cost analyses research questions. Most focused on individual level change, although changes in the broader multi-level context were proposed, but at times implicit, often viewed as process measures. A majority included aims related to understanding important mediator and moderator variables. Few explicated multilevel theories, although models reflected an ecological orientation.CONCLUSIONS: Future practice and research priorities include development of clear operational definitions of follow-up; conceptual and descriptive evaluations of how providers, patients, and organizations interact across the steps and interfaces of follow-up care; determination of priorities for multilevel intervention testing and improvement of measures, and application of appropriate and innovative study designs using multi-methods.This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. HHSN261200800001E. Cancer Epidemiol Biomarkers Prev; 21(3); 1-9. ©2012 AACR.

Observed Social Support Behaviors and Cancer-Related Cognitive Processing in Couples Coping with Head and Neck Cancer (HNC)

Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology. Feb, 2012  |  Pubmed ID: 22337544

Deficits in Health-Promoting Behaviors Among Veteran and Non-Veteran Male Cancer Survivors in Texas

Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology. Feb, 2012  |  Pubmed ID: 22337548

OBJECTIVES: Cancer survivors may have increased risk for additional malignancies and illnesses. Veterans comprise a significant proportion of Texas male cancer survivors and may differ in their health status and needs from non-veterans. It is unknown whether they differ in general health-promotion strategies. This study sought to identify deficits in health-promoting behaviors among Texas male cancer survivors and to determine whether veteran-status predicts differences along these behaviors.METHODS: Using the Behavioral Risk Factor Surveillance System 2009 survey, we conducted secondary analysis of 280 veteran and 250 non-veteran Texas male cancer survivors. Data were analyzed using Fisher's exact test and logistic-regression models.RESULTS: Survivors averaged 68 years (SD = 11.4) and were primarily white (93%), married (71.5%), college graduates (51%), and non-smokers (91%). Respondents reported several different cancer diagnoses; most commonly prostate (28%). More non-veterans than veterans were obese (31.6% vs. 22.5%; p = 0.03). Veteran-status was not associated with other co-morbidities, current smoking, binge drinking, or fruit/vegetable consumption. However, only 22% met recommendations for daily fruits/vegetables. In multivariate regression, veterans were less likely to meet moderate (OR = 0.54, 95% CI = 0.30-0.95) and vigorous (OR = 0.67, 95% CI = 0.45-0.99) physical-activity recommendations, but were more likely to have had health examinations within the previous year (OR = 1.77, 95% CI = 1.11-2.83).CONCLUSION: Texas male cancer survivors reported deficits across important health behaviors, including dietary and physical-activity recommendations. Veterans reported low compliance with physical-activity guidelines, in spite of evidence-based veterans health-promotion programs, e.g., MOVE! ®. Our results suggest veterans' adherence to routine care may offer a point of intervention to implement health-promotion guidelines among cancer survivors. Further research is needed to understand how to use the growing focus on cancer survivorship within the VA healthcare system to encourage greater adoption of health promotion practices among veteran cancer survivors. Cancer Epidemiol Biomarkers Prev; 21(3); 1-9. ©2012 AACR.

Discrimination of Three Pegaga (Centella) Varieties and Determination of Growth-lighting Effects on Metabolites Content Based on the Chemometry of 1H Nuclear Magnetic Resonance Spectroscopy

Journal of Agricultural and Food Chemistry. Jan, 2012  |  Pubmed ID: 22084897

The metabolites of three species of Apiaceae, also known as Pegaga, were analyzed utilizing (1)H NMR spectroscopy and multivariate data analysis. Principal component analysis (PCA) and hierarchical cluster analysis (HCA) resolved the species, Centella asiatica, Hydrocotyle bonariensis, and Hydrocotyle sibthorpioides, into three clusters. The saponins, asiaticoside and madecassoside, along with chlorogenic acids were the metabolites that contributed most to the separation. Furthermore, the effects of growth-lighting condition to metabolite contents were also investigated. The extracts of C. asiatica grown in full-day light exposure exhibited a stronger radical scavenging activity and contained more triterpenes (asiaticoside and madecassoside), flavonoids, and chlorogenic acids as compared to plants grown in 50% shade. This study established the potential of using a combination of (1)H NMR spectroscopy and multivariate data analyses in differentiating three closely related species and the effects of growth lighting, based on their metabolite contents and identification of the markers contributing to their differences.

Activated Human Hydroxy-Carboxylic Acid Receptor-3 Signals to MAP Kinase Cascades Via the PLC-Dependent PKC and MMP-Mediated EGFR Pathways

British Journal of Pharmacology. Jan, 2012  |  Pubmed ID: 22289163

Background and purpose:  The orphan G protein-coupled receptor HCA(3) , has recently been identified as a receptor for 3-hydroxy-octanoate, is of particular interest given its ability to treat lipid disorders and atherosclerosis. Here we demonstrate the pathway of HCA(3) -mediated activation of extracellular signal-regulated kinases 1 and 2 (ERK1/2). Experimental approach:  Using CHO-K1 cells stably expressing HCA(3) and A431 cells, a human epidermoid cell line with high levels of endogenous expression of functional HCA(3) receptors, HCA(3) -mediated activation of ERK1/2 was measured by western blot. Key results:  HCA(3) -mediated activation of ERK1/2 was rapid, peaking at 5 min, and was pertussis toxin-sensitive. Our data obtained by time course analyses in combination with different kinase inhibitors demonstrated that upon agonist stimulation, HCA(3 ) evoked ERK1/2 activation via two distinct pathways, the PLC/PKC pathway at early time points (≤2 min) and the MMP/EGFR transactivation pathway with a maximum response at 5 min. Furthermore, the present results also indicated that the βγ-subunits play a critical role in HCA(3) -activated ERK1/2 phosphorylation, whereas β-arrestins and Src were not required for ERK1/2 activation. Conclusions and Implications:  We document the molecular mechanisms underlying the coupling of human HCA(3) to the ERK1/2 MAP kinase pathway in CHO-K1 and A431 cells, which implicate the G(i) protein-initiated, PLC/PKC- and PDGFR/EGFR transactivation-dependent pathways. These observations may provide new insights into the pharmacological effects and the physiological functions modulated by the HCA(3) -mediated activation of ERK1/2.

Implantation of the Common Cavity Malformation May Prevent Meningitis

Cochlear Implants International. Feb, 2012  |  Pubmed ID: 22333042

Objectives and importance: Children with certain congenital malformations of the inner ear, including those with a common cavity defect, have a higher incidence of spontaneous cerebrospinal fluid (CSF) leak and resulting meningitis. However, they may also benefit from cochlear implantation. We suggest that surgical management may be possible that both prevents meningitis and provides hearing rehabilitation during the same procedure. CLINICAL PRESENTATION: A 2-year-old girl with bilateral common cavity defects who had previously undergone cochlear implantation developed contralateral CSF leak resulting in meningitis. INTERVENTION: After resolution of the infection, cochlear implantation was performed at the same time as definitive CSF leak repair. Simultaneous cochlear implantation and repair of the CSF leak successfully decreased the chance of recurrent meningitis in this case. She has been deriving hearing benefit from the bilateral implants. CONCLUSION: This case suggests a role for cochlear implantation to be combined with simultaneous CSF leak repair in children with a cochlear malformation. Furthermore, bilateral cochlear implantation at an early age may be warranted in these patients before CSF leaks and meningitis have occurred.