bluuebunny/crossref_metadata_2025 huggingface dataset:
Leukaemia cell drug resistance and prognostic factors in AML
Authors: Nørgaard Jan M. , Olesen Gitte , Kristensen Jørgen S. , Pedersen Bent , Hokland Peter
Published: July 2010

Abstract: In 93 cases of acute myeloid leukaemia (AML) the extent to which prognostic factors mirrored the in vitro cellular chemotherapy resistance (to anthracyclines aclarubicin (Acla) and daunorubicin (Dau) as well as nucleoside analogue cytarabine (Ara‐C)) was investigated using a 4‐d MTT (3‐[4,5‐dimethylthiazol‐2‐yl]‐2,5‐diphenyl tetrazolium bromide) assay. We found that age at presentation and presence of secondary AML were significantly correlated to leukaemia cell Ara‐C resistance. Thus, analysis of in vitro drug resistance data revealed that age at presentation and presence of secondary leukaemia were both independently correlated to cellular drug resistance, with older age being associated with higher Ara‐C resistance in vitro (p = 0.02 and 0.01 in univariate and multivariate analyses, respectively) and with secondary leukaemia being associated with higher Ara‐C resistance (p = 0.04 and 0.059 in univariate and multivariate analysis, respectively). Median LC‐50 values (Ara‐C) were: 178 ng/ml in paediatric cases, 356 ng/ml in younger adult cases, and 584 ng/ml in elderly (age ≥ 60 yr) cases giving a resistance ratio between these age subgroups of 1:2.0:3.3. Median LC‐50 values (Ara‐C) was 381 ng/ml in de novo cases as opposed to 891 ng/ml (resistance ratio 1:2.3) in secondary cases. By contrast, cytogenetic findings, presenting leucocyte count, FAB‐subtype, and gender were not consistently correlated to in vitro drug resistance to any of the three drugs. We conclude that at least two major adverse prognostic factors in AML (advanced age at presentation and presence of secondary leukaemia) are associated with increased leukaemia cell Ara‐C resistance. High leucocyte count is not associated with increased cellular drug resistance towards Acla, Ara‐C or Dau.
Response rate and survival after conventional chemotherapy for multiple myeloma by hospitals with different inclusion rates of patients to the trials. A Finnish Leukemia Group study
Authors: Oivanen T. , Kellokumpu‐Lehtinen P. , Koivisto A‐M. , Koivunen E.
Published: July 2010

Abstract: The purpose of this study was to analyse the influence of the hospital size, measured as the number of annual patient enrolments in the Finnish Leukaemia Group trials in the period 1979–85, on response rate and survival after conventional chemotherapy for multiple myeloma. The 432 myeloma patients for this study were derived from 4 prospective multicentre trials of the Finnish Leukaemia Group. The comparisons of the response rate to primary chemotherapy, progression‐free survival time (PFS), response rate after first relapse and overall survival time (OS) were made between patients treated in 3 hospital categories according to annual enrolment rate. 273 of the patients had been treated in “large” hospitals, 120 in “intermediate” and 38 in “small” ones. The median OS of patients aged up to 70 yr was 49 months and that of patients older than 70 yr was 31 months. There were no significant differences in response rate, PFS, response rate after first relapse and OS between the hospital categories. The most important endpoints in the treatment of multiple myeloma, response rate, PFS and OS are independent of the size of the hospital, measured as the number of annual patient entries in the trial. This allows the decentralisation of the conventional chemotherapy of multiple myeloma, within the framework of properly organised clinical trials.
Chronic idiopathic neutropenia of adults is associated with decreased bone mineral density and alterations in bone turnover biochemical markers
Authors: Papadaki Helen A. , Margioris Andrew N. , Miliaki Maria , Steriopoulos Constantin , Valatas William , Eliopoulos George D.
Published: July 2010

Abstract:  The aim of this study was to assess bone mineral density (BMD) and biochemical indices of bone metabolism in patients with chronic idiopathic neutropenia of adults (CINA) and define the relationships, if any, between these parameters and serum levels of interleukin‐1β (IL‐1β) and tumour necrosis factor‐α (TNF‐α), two cytokines normally involved in bone metabolism. Femoral neck BMD, serum osteocalcin (OC), bone‐specific alkaline phosphatase (BAP) and type I procollagen carboxy‐terminal propeptide (PICP), as well as urine‐free deoxypyridoline (Dpd) cross‐links, N‐telopeptide (NTx) and C‐telopeptide (CTx) cross‐links of type I of collagen were measured in 45 CINA patients and 36 normal subjects. Patients were arbitrarily classified in two groups, A and B, as having mild (neutrophils 1700–2500/μl) or ‘pronounced’ (neutrophils<1700/μl) neutropenia, respectively. BMD values were found significantly reduced in both groups of patients, compared to controls, and they strongly correlated with the number of circulating neutrophils. Serum OC and urinary NTx were significantly increased in patients of group B. Both serum OC and urinary NTx correlated inversely with the number of circulating neutrophils. Serum BAP and PICP and urine Dpd and CTx were within normal range. Serum IL‐1β and TNF‐α were elevated in both groups of patients and correlated inversely with the number of circulating neutrophils and the values of BMD. In addition, TNF‐α, but not IL‐1β, inversely correlated with OC and NTx. These findings indicate that CINA patients have biochemical evidence of increased bone turnover which leads to decreased BMD. The elevated serum IL‐1β and TNF‐α concentrations, suggestive of an underlying chronic inflammatory process in these patients, may be part of a mechanism accelerating bone turnover which, if prolonged, causes lowering of BMD.
Interferon alfa 2b as maintenance therapy in poor risk diffuse large B‐cell lymphoma in complete remission after intensive CHOP–BLEO regimens
Authors: Avilés Agustin , Cleto Sergio , Huerta‐Guzmán Judith , Neri Natividad
Published: July 2010

Abstract: Objectives: We conducted a randomized clinical trial to evaluate the role of interferon alfa 2b (IFN) as maintenance therapy in patients with diffuse large B‐cell lymphoma with high or high–intermediate clinical risk on complete remission (CR) after CHOP–BLEO regimens. Methods: Patients were initially treated with CHOP–BLEO regimens (which include increased doses of cyclophosphamide and epirubicine, instead of doxorubicin). If the patients achieved CR they were randomly assigned to receive either maintenance therapy with IFN 5.0 MU, three times at week by 1 yr, or no treatment (control group). Results: Two hundred and twenty‐three patients were considered as candidates for the study. They were of high (80%) or high–intermediate (20%) clinical risk; additionaly most patients had poor prognostic factors such as high levels of beta 2 microglobulin, lactic dehydrogenase levels, bulky disease (defined as a tumor mass >10 cm) or multiple extranodal involvement. In an intent‐to‐treat analysis all patients were evaluable to efficacy and toxicity. Median follow‐up was 45 months, the estimated 5‐yr overall survival and event‐free survival (EFS) for patients who received IFN were 71% (95% confidence interval (CI): 61–83%) and 57% (95% CI: 39–69%), respectively, values which were not statistically different from the control group: 69% (95% CI: 63–79%) and 54% (95% CI: 37–63%), respectively (p=0.2). Toxicity was mild. Conclusions: These results suggest that IFN used as maintenance therapy at these doses and schedules is not useful in aggressive malignant lymphoma when more intensive chemotherapy has been employed during induction treatment. Nevertheless, follow‐up is too short, and long‐term follow‐up would be necessary in order to draw definitive conclusions. Probably, an multicenter study is necessary to define the role of IFN as maintenance therapy in this patient setting.
Fatal upper and lower gastrointestinal cytomegalovirus disease following autologous peripheral blood stem cell transplantation
Authors: Perez‐Ceballos E. , Vallejo C. , Cano H. , Ayala F. , Martínez F. , Moraleda J. M. , Vicente V.
Published: July 2010

Abstract: Although the life‐threatening cytomegalovirus (CMV) disease is a well known complication following allogeneic hematopoietic stem cell transplantation (HSCT), it has been considered infrequent after autologous peripheral blood stem cell transplantation (PBSCT). On the other hand, the massive involvement of the gastrointestinal (GI) tract as the primary site of fatal CMV disease is particularly rare after autologous PBSCT. We present the case of a woman who suffered from CMV disease after high‐dose busulphan/melphalan/thiotepa (BuMelTT) and autologous PBSCT. The primary site of infection was the GI tract, which was extensively affected. During the fifth week post‐transplant the patient started with epigastralgia, diarrhea, fever, GI bleeding, and thrombocytopenia, and she died on day +52. Another case of fatal CMV disease among the few patients treated with BuMelTT has been recently reported, which suggests that the immunodeficiency associated with that regimen can be as intense as that occurring after allogeneic BMT.
The John Ultmann lecture – the role of radiation therapy in the treatment of Hodgkin's disease: past, present, and future
Authors: Hoppe Richard T.
Published: July 2010

Abstract:  Radiation therapy has been used in the treatment of Hodgkin's disease for more than a century. At first it was demonstrated to provide significant palliation. As advances in technology permitted a more controlled delivery of radiation to defined regions, long lasting responses of disease were demonstrated. Beginning in the mid‐1960s, Vera Peters and Henry Kaplan demonstrated the curative potential of high dose extended field irradiation in the treatment of stage I‐II Hodgkin's disease. As effective programs of chemotherapy evolved, combined modality therapy with intensive chemotherapy and extensive radiation was applied for patients with early stage disease, resulting in significant morbidity and some mortality. More recently, combined modality programs of brief chemotherapy and limited radiation have been extremely successful in managing patients with stage I‐II disease. In addition to its utility in early disease, radiation therapy is an integral component of treatment programs for patients with large mediastinal adenopathy. It has also proved useful in patients with stage III‐IV who achieve only a partial response to chemotherapy and may also have a role to play as a component of high‐dose therapy hematopoietic stem cell transplant programs. Radiation therapy remains the most effective single agent for the treatment of Hodgkin's disease.
Comparison of oral mucosal pH values in bulimia nervosa, GERD, BMS patients and healthy population
Authors: Aframian DJ , Ofir M , Benoliel R
Published: July 2010

Oral Diseases (2010) 16, 807–811

Objectives:  The aim of this study was to compare the oral mucosal pH in healthy individuals to patients with gastroesophageal reflux disease (GERD), Bulimia nervosa (BN) and burning mouth syndrome (BMS).

Subjects and methods:  Using a flat pH meter sensor, pH levels were established in eight mucosal sites in 26 healthy individuals, 26 GERD patients, 22 BN patients and 29 BMS patients.

Results:  A significantly lower pH was found in the BN and GERD groups (6.38 ± 00.45, 6.51 ± 0.32 respectively, P < 0.05) and a higher, but non‐significant, pH level in the BMS group (7.01 ± 0.34, P > 0.05) compared with the control (C) group (6.82 ± 0.33).

Conclusions:  BMS patients showed no pH differences from C group. The mucosa of BN and GERD patients was significantly acidic relative with controls; thus this simple technique may serve as a diagnostic tool for identifying gastro‐esophageal conditions.
Application of self‐efficacy theory in dental clinical practice
Authors: Kakudate N , Morita M , Fukuhara S , Sugai M , Nagayama M , Kawanami M , Chiba I
Published: July 2010

Oral Diseases (2010) 16, 747–752

In clinical practice, self‐efficacy refers to how certain a patient feels about his or her ability to take the necessary action to improve the indicators and maintenance of health. It is assumed that the prognosis for patient behaviour can be improved by assessing the proficiency of their self‐efficacy through providing psychoeducational instructions adapted for individual patients, and promoting behavioural change for self‐care. Therefore, accurate assessment of self‐efficacy is an important key in daily clinical preventive care. The previous research showed that the self‐efficacy scale scores predicted patient behaviour in periodontal patients and mother’s behaviour in paediatric dental practice. Self‐efficacy belief is constructed from four principal sources of information: enactive mastery experience, vicarious experience, verbal persuasion, and physiological and affective states. Thus, self‐efficacy can be enhanced by the intervention exploiting these sources. The previous studies revealed that behavioural interventions to enhance self‐efficacy improved oral‐care behaviour of patients. Therefore, assessment and enhancement of oral‐care specific self‐efficacy is important to promote behaviour modification in clinical dental practice. However, more researches are needed to evaluate the suitability of the intervention method.
Convenient and reproducible in vivo gene transfer to mouse parotid glands
Authors: Zheng C , Shinomiya T , Goldsmith CM , Di Pasquale G , Baum BJ
Published: July 2010

Oral Diseases (2010) 17, 77–82

Objectives:  Published studies of gene transfer to mouse salivary glands have not employed the parotid glands. Parotid glands are the likely target tissue for most clinical applications of salivary gene transfer. The purpose of the present study was to develop a convenient and reproducible method of retroductal gene transfer to mouse parotid glands.

Methods:  The volume for vector delivery was assessed by infusion of Toluidine Blue into Stensen’s ducts of Balb/c mice after direct intraoral cannulation. Recombinant, serotype 5 adenoviral vectors, encoding either firefly luciferase or human erythropoietin (hEpo), were constructed and then administered to parotid glands (107 vector particles/gland). Transgene expression in vivo was measured by enzyme activity (luciferase) or an enzyme‐linked immunosorbent assay (hEpo). Vector biodistribution was measured by real‐time quantitative (Q) PCR.

Results:  The chosen volume for mouse parotid vector delivery was 20 μL. Little vector was detected outside of the targeted glands, with both QPCR and luciferase assays. Transgene expression was readily detected in glands (luciferase, hEpo), and serum and saliva (hEpo). Most secreted hEpo was detected in saliva.

Conclusion:  These studies show that mouse parotid glands can be conveniently and reproducibly targeted for gene transfer, and should be useful for pre‐clinical studies with many murine disease models.
A rare case of local relapsing oral melanoma
Authors: Gauwerky Katharina J. , Ehrenfeld Michael , Bakos Renato M. , Volkenandt Matthias , Ruzicka Thomas , Berking Carola
Published: July 2010

Melanoma of the oral mucosa is an extremely rare tumor. At the time of diagnosis most melanomas are in an advanced stage because of few clinical signs. Therefore the prognosis of melanoma of the oral mucosa is often very poor. We present a 48‐year‐old patient with melanoma of the oral mucosa first diagnosed 22 years ago. Over 20 years several wide excisions were necessary because of multiple local relapses. Eventually, the patient died from brain metastases.
MRSA in dermatology – Prospective epidemiological study in employees and patients of a dermatological department of a university hospital
Authors: Reich‐Schupke Stefanie , Geis Gabriele , Reising Matthias , Altmeyer Peter , Stücker Markus
Published: July 2010

Background: In recent years, the prevalence of MRSA has increased worldwide. There is a lack of systematic epidemiological studies evaluating the prevalence of MRSA in dermatology in Germany.

Objective: What is the prevalence of MRSA in the employees and hospitalized patients in a dermatological department? What dermatological diagnoses have the highest risk for MRSA?

Patients and methods: Nasal swabs taken twice (at admission and discharge) from all consenting hospitalized patients and once from all consenting employees were analyzed for MRSA.

Results: Analysis von 798 swabs (715 patients, 83 employees). Detection of MRSA in 31 swabs (MRSA rates: all = 4.3 %, patients = 3.7 %, employees = 4.8 %). Patients with a chronic leg ulcer had a significantly increased risk for MRSA (p = 0.03). Increased MRSA rates without statistical significance were found for men, patients with at least one hospitalization during the last 12 weeks and a hospitalization of at least 5 days. None of the patients with psoriasis had MRSA. Conclusions: In comparison to international studies, the prevalence of MRSA in the current study is in the lower third. In dermatology, patients with a chronic leg ulcer have an increased risk for MRSA and should be screened at admission. A general screening for MRSA seems to be not reasonable in view of the low MRSA rates in the investigated department.
Chronic Treatment with Quercetin does not Inhibit Angiotensin‐Converting Enzyme In Vivo or In Vitro
Authors: Neto‐Neves Evandro Manoel , Montenegro Marcelo F. , Dias‐Junior Carlos A. , Spiller Fernando , Kanashiro Alexandre , Tanus‐Santos Jose E.
Published: July 2010

Abstract:  The precise mechanisms explaining the anti‐hypertensive effects produced by quercetin are not fully known. Here, we tested the hypothesis that chronic quercetin treatment inhibits the angiotensin‐converting enzyme (ACE). We examined whether quercetin treatment for 14 days reduces in vivo responses to angiotensin I or enhances the responses to bradykinin in anaesthetised rats. We measured the changes in systemic arterial pressure induced by angiotensin I in doses of 0.03–10 μg/kg, by angiotensin II in doses of 0.01–3 μg/kg, and to bradykinin in doses of 0.03–10 μg/kg in anaesthetised rats pre‐treated with vehicle (controls), or daily quercetin 10 mg/kg intraperitoneally for 14 days, or a single i.v. dose of captopril 2 mg/kg. Plasma ACE activity was determined by a fluorometric method. Plasma quercetin concentrations were assessed by high performance liquid chromatography. Quercetin treatment induced no significant changes in the hypertensive responses to angiotensin I and angiotensin II, as well in the hypotensive responses to bradykinin (all p > 0.05). Conversely, as expected, a single dose of captopril inhibited the hypertensive responses to angiotensin I and potentiated the bradykinin responses (all p < 0.01), while no change was found in the vascular responses to angiotensin II (all p > 0.05). In addition, although we found significant amounts of quercetin in plasma samples (mean = 206 ng/mL), no significant differences were found in plasma ACE activity in rats treated with quercetin compared with those found in the control group (50 ± 6 his‐leu nmol/min/mL and 40 ± 7 his‐leu nmol/min/mL, respectively; p > 0.05). These findings provide strong evidence indicating that quercetin does not inhibit ACE in vivo or in vitro and indicate that other mechanisms are probably involved in the antihypertensive and protective cardiovascular effects associated with quercetin.
Between a Pristine Myth and an Impoverished Future
Authors: Clement Charles R. , Junqueira André B.
Published: July 2010

Early European naturalists saw Amazonian landscapes as pristine, but modern research has found a complex historical ecology, similar to that of other tropical and temperate regions. Although the pristine myth has been thoroughly debunked, too many biodiversity researchers fail to incorporate historical ecology into their analyses. For a world society out of balance with its natural resource base, careful interpretation is essential to understand trends, including impoverishment of planetary biodiversity. If world society avoids civilizational collapse, parts of Amazonia's historical ecology can contribute to future sustainability and improved survival of its biodiversity.
Will Tropical Biodiversity Survive our Approach to Global Change?
Authors: ter Steege Hans
Published: July 2010

Because global change is almost synonymous with climate change, research has emphasized perhaps too much the effects of climate change over other global concerns that might be equally detrimental to biodiversity and humanity. These include unsustainable land use and massive conversion and degradation of natural habitats. Perhaps by the time we understand the effects of global climate change on tropical forests, there may not be any left to admire.
He Iwi Kotahi Tatou Trust: Post‐development practices in Moerewa, Northland
Authors: FitzHerbert Stephen , Lewis Nicolas
Published: July 2010

This paper examines community development projects in Moerewa, a small town in Te Tai Tokerau (central Northland) decimated by industrial decline in the late 1980s. It builds on a series of conversations with Ngahau Davis of He Iwi Kotahi Tatou Trust, which has sought to revitalise Moerewa by challenging conventional understandings of development. The paper is part of an on‐going engagement with the Trust, which includes involving it with a second year undergraduate field course. In the paper, we argue for the political and theoretical potential of post‐development inquiry and practice in communities like Moerewa.
(Re)making space for kiwi: beyond ‘fortress conservation’ in Northland
Authors: Blue Lyndsay , Blunden Greg
Published: July 2010

Mainstream conservation has been long dominated globally by the protected area paradigm. This approach has been widely challenged in recent years, and new conservation initiatives have emerged. The situation is mirrored in New Zealand, where ongoing biodiversity loss has prompted reappraisal. Within this context, we highlight the plight of kiwi, focusing on Northland and efforts there to (re)make space for this iconic bird which is at risk of extinction. While the state has primarily responded by fortifying ‘islands’ on public conservation land, Far North communities are working in a variety of ways and localities, both within and beyond ‘the fortress’, to secure a future for the ‘people's bird’.
Note on genus Achlya Billberg, 1820 from China (Lepidoptera, Thyatiridae)
Authors: PAN Zhao‐Hui , ZHOU Yong‐Quan , HAN Hui‐Lin
Published: July 2010

The genus Achlya Billberg, 1820 is reported for the first time from China as A. jezoensis (Matsumura, 1927), which is a species collected from Maorshan, Heilongjiang Province. The adult and genitalia characters of the species are briefly redescribed and illustrated, distribution data is provided.
Effects of auditory stimuli on the lifespan of Drosophila melanogaster
Authors: MORALES Robin F. , SEONG Ki Moon , KIM Cha Soon , JIN Young‐Woo , MIN Kyung‐Jin
Published: July 2010

It is well known that music can have calming effects on humans, other mammals and birds. Reducing environmental stress or enhancing the resistance to certain stressors has been shown to extend lifespan in several organisms. Evidence also suggests that mild temporary stress may also enhance stress resistance and ultimately slow the aging process. This study explored the possibility that music may influence the lifespan of the fruit fly Drosophila melanogaster, possibly by affecting responses to stress. Flies received either background sounds (control), or background sounds supplemented with music (experimental). The experimental group had classical music playing constantly at an average of 20 dB above background sound. The median lifespan of females receiving music was 42 days compared to the median of 45 days without music, but the difference was not significant. For males median lifespans were 42 days with music exposure, and 47 days without music and the difference was significant. These results suggest that exposure to classical music decreased the lifespan of male Drosophila. Both experimental and control populations showed age‐dependent increases in mortality, indicating that music affects the normal aging process rather than showing overt toxicity. These results suggest that certain auditory stimuli may be stressful and can be used as insect management.
Does the Oxidative/Glycolytic Ratio Determine Proliferation or Death in Immune Recognition?
Authors: NEWELL M. KAREN , HARPER MARY‐ELLEN , FORTNER KAREN , DESBARATS JULIE , RUSSO ALICIA , HUBER SALLY A.
Published: July 2010

Here we discuss the possibility that the way cells utilize fuel(s) for energy confers the properties that can be recognized by the immune system and, reciprocally, that recognition by the immune system can alter the balance of the cell's energy metabolism. We propose that immune recognition, of somatic cells via MHC can alter the their energy metabolism and induce a metabolic shift. We demonstrate the reciprocal relationship that inducing a shift in metabolism toward glycolysis by supplying glucose and insulin results in the upregulation of immunologically recognizable molecules such as cell surface Fas. Thus, immune recognition can induce metabolic deviation. Metabolic deviation can result in altered immune recognition and ultimately in cell proliferation, cell differentiation, or cell death.
Molecular Basis of the α‐MSH/IL‐1 Antagonism
Authors: BRZOSKA T. , KALDEN D.‐H. , SCHOLZEN T. , LUGER T. A.
Published: July 2010

ABSTRACT: The neuropeptide α‐melanocyte stimulating hormone (α‐MSH) is recognized as a potent mediator of immune and inflammatory reactions. Accordingly, α‐MSH in vitro, as well as in vivo, antagonizes the proinflammatory activities of cytokines such as interleukin‐1 (IL‐1), IL‐6, and tumor necrosis factor a (TNFα). Since the molecular basis of these antiinflammatory effects is not well known, the influence of α‐MSH on IL‐1β‐induced chemokine production and transcription factor activation was investigated in human keratinocytes. α‐MSH, in a dose‐dependent manner, after 48 h, significantly reduced the IL‐1b mediated secretion of the C‐X‐C chemokines IL‐8 and Groα. This was confirmed by semiquantitative RT‐PCR, which revealed a marked downregulation in IL‐8 and Groα mRNA expression. Furthermore, we determined the effect of α‐MSH on the IL‐1β‐induced activation of the nuclear factor κB (NFκB)‐a major transcription factor for chemokine genes. Electrophoretic mobility‐shift‐assays showed that α‐MSH, in a dose range from 10−6 to 10−12 M, significantly downregulated the IL‐1b‐induced activation of NFκB 10 minutes after stimulation. Therefore, NFκB inactivation by α‐MSH appears to be a crucial event, one that is responsible for the downregulation of cytokine gene transcription.
POMC and Fibroblast Biology
Authors: LOTTI TORELLO , TEOFOLI PATRIZIA , BIANCHI BEATRICE , MAUVIEL ALAIN
Published: July 2010

ABSTRACT: We evidenced in vitro proopiomelanocortin (POMC) mRNA‐transcription in human dermal fibroblasts using Northern blot hybridization. Modulation of POMC gene expression by cytokines (transforming growth factor‐β, TGF‐β, and tumor necrosis factor‐α, TNF‐α) was investigated by incubating human normal fibroblasts with 1 and 10 ng/ml cytokines, either alone or in combination, for 24 hours. Our results show that dermal fibroblasts express POMC at significant levels under unstimulated conditions. POMC steady‐state levels were significantly reduced by addition of TGF‐β. On the other hand, TNF‐α exerted a stimulatory effect on POMC mRNA transcription, partially counteracting the effect of TGF‐β. These data provide the first demonstration of POMC gene expression in cultured skin fibroblasts. The opposite regulatory effect of TGF‐β and TNF‐α, two cytokines primarily involved in extracellular matrix regulation, suggests a possible role for POMC‐derived peptides in fibroblast activity. We also investigated POMC mRNA expression in keloid‐derived fibroblasts in culture, and its regulation by TGF‐β added at the highest concentration documented for inhibition. Keloid‐derived fibroblasts showed clearly detectable levels of POMC mRNA in basal conditions, and no alteration of POMC gene expression was observed when TGF‐β was added in culture. The altered TGF‐β regulation of POMC mRNA levels suggest that POMC‐derived peptides may play a role in the pathogenesis of keloid formation through an autocrine/paracrine network, resulting in modulation of extracellular matrix synthesis.
Ibogaine: Complex Pharmacokinetics, Concerns for Safety, and Preliminary Efficacy Measures
Authors: MASH DEBORAH C. , KOVERA CRAIG A. , PABLO JOHN , TYNDALE RACHEL F. , ERVIN FRANK D. , WILLIAMS IZBEN C. , SINGLETON EDWARD G. , MAYOR MANNY
Published: July 2010

Ibogaine is an indole alkaloid found in the roots of Tabernanthe Iboga (Apocynaceae family), a rain forest shrub that is native to western Africa. Ibogaine is used by indigenous peoples in low doses to combat fatigue, hunger and thirst, and in higher doses as a sacrament in religious rituals. Members of American and European addict self‐help groups have claimed that ibogaine promotes long‐term drug abstinence from addictive substances, including psychostimulants and opiates. Anecdotal reports attest that a single dose of ibogaine eliminates opiate withdrawal symptoms and reduces drug craving for extended periods of time. The purported efficacy of ibogaine for the treatment of drug dependence may be due in part to an active metabolite. The majority of ibogaine biotransformation proceeds via CYP2D6, including the O‐demethylation of ibogaine to 12‐hydroxyibogamine (noribogaine). Blood concentration‐time effect profiles of ibogaine and noribogaine obtained for individual subjects after single oral dose administrations demonstrate complex pharmacokinetic profiles. Ibogaine has shown preliminary efficacy for opiate detoxification and for short‐term stabilization of drug‐dependent persons as they prepare to enter substance abuse treatment. We report here that ibogaine significantly decreased craving for cocaine and heroin during inpatient detoxification. Self‐reports of depressive symptoms were also significantly lower after ibogaine treatment and at 30 days after program discharge. Because ibogaine is cleared rapidly from the blood, the beneficial aftereffects of the drug on craving and depressed mood may be related to the effects of noribogaine on the central nervous system.
Characterization and Molecular Localization of Anion Transporters in Colonic Epithelial Cells
Authors: RAJENDRAN VAZHAIKKURICHI M. , BINDER HENRY J.
Published: July 2010

Abstract: This study describes the identification and characterization of anion transporters in apical membrane (APM) and basolateral membrane (BLM) of rat distal colon. Cl‐HCO3, Cl‐OH, Cl‐butyrate, and butyrate‐HCO3 exchanges and Na‐HCO3 cotransporter are present in rat distal epithelial cells. Cl‐HCO3 exchange (1) is present only in APM from surface, but not from crypt cells; (2) is also present in BLM; and (3) of surface cell is encoded by anion exchange (AE)‐1 isoform, whereas BLM Cl‐HCO3 is encoded by AE2 isoform. Cl‐OH exchange is present only in APM, but not in BLM from surface and crypt cells, and is responsible for regulation of cell functions (i.e., cell pH and cell volume regulation). Butyrate‐HCO3 exchange (1) is also present in apical membrane vesicles (AMV) from surface, but not from crypt cells; (2) is present in BLM; and (3) is responsible for SCFA‐dependent HCO3 secretion. By contrast, Cl‐butyrate exchange: (1) is present in APM from both surface and crypt cells; (2) is not present in BLM; and (3) recycles butyrate by absorbing Cl. NaHCO3 cotransport: (1) is present only in BLM; (2) is expressed predominantly in midcrypt regions; and (3) may be linked to HCO3 secretion. A mechanism for HCO3 movement across the crypt apical membrane has not as yet been identified.
Neurotransmitters in Neuronal Reflexes Regulating Intestinal Secretion
Authors: COOKE HELEN J.
Published: July 2010

Abstract: The intestinal crypt cell secretes chloride into the lumen, resulting in accumulation of fluid that normally thins out mucus or, at higher secretory rates, flushes out the contents. The regulation of chloride secretion occurs by neural reflex pathways within the enteric nervous system. Mechanical stimulation releases 5‐hydroxytryptamine (5‐HT) from enterochromaffin cells with subsequent activation of intrinsic primary afferents that carry electrical signals to submucosal ganglia. After processing, interneurons activate cholinergic and vasoactive intestinal peptide (VIP) secretomotor neurons. Acetylcholine and VIP bind to epithelial receptors and stimulate sodium chloride and fluid secretion. Reflex‐evoked secretory rates can be modulated by a variety of mediators at the level of the enterochromaffin cells, neurons within the reflex pathway, or epithelial cells. Understanding the complex regulatory mechanisms for chloride secretion is likely to provide mechanistic insights into constipation and diarrhea.
Neutrophil Migration across Intestinal Epithelium
Authors: JAYE DAVID L. , PARKOS CHARLES A.
Published: July 2010

Abstract: Transmigration of neutrophils across epithelial surfaces is the hall‐mark of inflammatory mucosal diseases of diverse organs. In disorders such as Crohn's disease, ulcerative colitis, pyelonephritis, and bronchitis, for example, neutrophil transmigration correlates with clinical disease activity, is associated morphologically with injury to the epithelium, and is central to disease pathophysiology. The mechanisms by which neutrophils transmigrate across epithelia are, therefore, of considerable significance for numerous pathologic states. In this paper, we discuss current evidence that defines these mechanisms in intestinal epithelium, emphasizing the structural constituents determining adhesive interactions and a subset of the complex regulatory signals between neutrophils and epithelium.
Enhanced Expression of iNOS in Inflamed Colons of IL‐2‐Deficient Mice Does Not Impair Colonic Epithelial Barrier Function
Authors: HARREN M. , BARMEYER C. , SCHMITZ H. , FROMM M. , HORAK I. , DIGNASS A. , JOHN M. , WIEDENMANN B. , SCHULZKE J.‐D.
Published: July 2010

Abstract: On the basis of recently observed high levels of iNOS expression that correlated with intestinal inflammation in interleukin‐2‐deficient [IL‐2(−/−)] mice, it was postulated that nitric oxide may damage colonic epithelial cells or impair intestinal epithelial barrier function. This damage may result in an increased permeability of the colonic epithelium leading to high antigenic exposure of the intestinal immune system, which may perpetuate chronic inflammation. Our data demonstrate that high expression of iNOS in IL‐2(−/−) mice is correlated with the length/weight ratio (L/W ratio), a widely accepted marker for intestinal inflammation. However, no reduction of epithelial resistance was observed, as would be expected in case of a damaged, leaky epithelium. Our results suggest that enhanced formation of NO in IL‐2(−/−) mice does not cause impairment of epithelial barrier function.
Analysis of Low‐Molecular‐Weight GTP‐Binding Proteins in Two Functionally Different Intestinal Epithelial Cell Lines
Authors: STEIN JÜRGEN , BAUSKE RUTH , GERHARD RALF
Published: July 2010

Abstract: Low molecular weight GTP‐binding proteins are molecular switches that are believed to play pivotal roles in cell growth, differentiation, cytoskeletal organization, and vesicular trafficking. In this study, for the first time, members of this family of proteins in two functionally different intestinal epithelial cell lines are identified and characterized. [α32P]GTP blot overlay assays of cytosolic and membranous fractions revealed the presence of specific GTP‐binding proteins in the range of 20‐30 kDa (small GTPases) in both fractions, with considerably higher amounts in the membranous insoluble fraction. Analysis by two‐dimensional electrophoresis, immunoprecipitation using monoclonal and sequence‐specific polyclonal antibodies, and C3 exoenzyme‐mediated ADP ribosylation demonstrated the presence of Ras, Rap, Rho, Rac, Rab, and several other small GTPases. The pattern of small GTP‐binding proteins corresponded to the characteristics of the cell lines. Caco‐2 cells showed a Rab5 protein that is known to be involved in endocytosis but was not found in T84 cells. On the contrary Rab3 has been shown to participate in secretory processes. It is highly expressed in T84 cells (sixfold compared to Caco‐2 cells).
World Trade, Disease and Florida's Animal Populations: The Changing Dynamics
Authors: COFFMAN LEROY M.
Published: July 2010

Abstract: One of florida's three leading economic industries is agriculture. Agriculture feeds and enhances the lives of millions of people in Florida, the united states, and the entire world. Agriculture in Florida results in more than $6 billion in farm cash receipts, employment for more than 60,000 people a month, more than $18 billion in farm‐related economic activity and stretches from the farm gate to the state's supermarkets with an impact of nearly $45 billion. The domestic and wild animal populations of Florida, our unique relationship to the Caribbean, Atlantic Ocean, Gulf of Mexico, Central and South America, as well as tourism, diverse human population growth and immigration, all add to the complexity of an environment capable of establishing many animals, animal pests and diseases not native to the United States. Never before have the dynamics of disease control involved as much challenge and diversity. Is the balance at risk, or is the risk over‐balanced? Can science, economics and politics blend to maintain this balance? How will the balance affect world trade, disease control and the animal populations of Florida?
OIE List A Disease as a Constraint to International Trade
Authors: KITCHING R. P.
Published: July 2010

Abstract: World Trade Organisation agreements have swept aside many of the previous constraints to international trade in animals and animal products and have looked critically at those that still survive. The presence of disease, in particular the OIE list A diseases, still provide legitimacy for barriers to trade, and as a consequence the importance of reliable animal disease surveillance has increased. However, the economic consequences of reporting the occurrence of a List A disease have also increased, as this provides trading partners with sufficient reason to impose an embargo that could severely compromise the national agricultural industry. The dilemma for some developing economies, reliant on agricultural exports, is how to balance a transparent and efficient disease reporting service, sufficient to provide the necessary information for importing countries to make realistic risk assessments, with the perceived political damage from being honest with trading partners who might take advantage of the information to require additional safeguards and health certification.
The Role of the World Reference Laboratories for Foot‐and‐Mouth Disease and for Rinderpest
Authors: KITCHING R. P.
Published: July 2010

Abstract: The World Reference Laboratories for Foot‐and‐Mouth Disease and for Rinderpest provide a worldwide diagnostic and surveillance service for these disease for FAO and OIE. Both laboratories are housed within the high security facility of the Institute for Animal Health, Pirbright, UK. Foot‐and‐mouth disease (FMD) and rinderpest (RP) are OIE List A diseases and historically have caused huge losses to agricultural economies around the world, prompting the establishment of veterinary colleges in Europe and environmentally controversial control programs in Africa. FMD and RP have now been geographically restricted, but the large legal and illegal world trade in live animals and animal products constantly threatens to allow them to spread back into disease‐free areas. The Reference Laboratories provide a center of excellence for the development of improved diagnostic techniques and a repository of isolates collected over many years. These libraries provide material for investigations of the molecular epidemiology and evolution of the viruses and a data base against which new isolates can be compared. Thus it is possible to individually characterize new outbreak strains, identify their likely origin and provide the most up‐to‐date support for their control.
Animal Trypanosomiasis in South America: Current Status, Partnership, and Information Technology
Authors: DÁVILA ALBERTO M.R. , SILVA ROBERTO AGUILAR M.S.
Published: July 2010

Abstract: Animal trypanosome species of economical importance in South America include T. vivax and T. evansi. Both species are described in Brazil, Bolivia, Colombia, French Guyana, Peru, Suriname, and Venezuela. In Argentina and Guyana, only T. evansi and T. vivax are found, respectively. Our studies on T. vivax indicated that the parasite was spreading around 1.3 km per day in Bolivia. We found severe leukopenia in bovines from Pantanal (Brazil) and the Department of Santa Cruz (Bolivia). Because it can cause immunosupression, the importance of trypanosomiasis control in ensuring success of vaccination campaigns against foot and mouth disease (FMD) in the Pantanal and Bolivia should be considered. The use of one needle for several animals during FMD campaigns in Brazil and Bolivia could also contribute to the spread of T. vivax. The anticipated losses due to T. vivax could exceed $160 million, assuming there are 11 million head of cattle in the Brazilian Pantanal and Bolivian lowlands. International collaboration among research institutes is needed to deal with these diseases and parasites. Previous efforts using information technologies resulted in the creation of two discussion lists (Tryplink and Trypan), the edition of the on‐line version of Trypnews and Internet conferences.
An in Vivo Model to Investigate Lymphocyte‐Mediated Immunity During Acute Hemoparasitic Infections: Use of a Monoclonal Antibody to Selectively Deplete CD4+ T Lymphocytes from Thymectomized Calves
Authors: VALDEZ R. A. , McGUIRE T. C. , BROWN W. C. , DAVIS W. C. , KNOWLES D. P.
Published: July 2010

Abstract: Thymectomized calves were selectively depleted of CD4+ T lymphocytes with a monoclonal antibody (mAb) specific for the bovine CD4 monomer (ILA‐11). Calves were treated with high loading doses of ILA‐11 during the first week of the study then treated with subsequent lower maintenance doses. Depletion of CD4+ T lymphocytes was assessed weekly by flow cytometric analysis of PBMC and mononuclear cells from lymph node and spleen biopsies. Treatment with high doses of ILA‐11 resulted in rapid and marked depletion of CD4+ T lymphocytes from the peripheral blood, peripheral lymph nodes, and spleen. Although CD4+ T lymphocytes slowly returned to the peripheral blood, peripheral lymph nodes, and spleen by day 21 post‐treatment, the numbers of CD4+ T lymphocytes in depleted calves remained below pre‐depletion levels for the duration of the study. CD4+ T lymphocytes failed to be effectively depleted from a non‐thymectomized calf treated with the mAb ILA‐11. Development of a T lymphocyte depletion model in thymectomized calves will permit testing of the hypothesis that CD4+ T lymphocytes and IFN‐γ are required in cattle for control of acute anaplasmosis. In subsequent planned studies, thymectomized calves depleted of CD4+ T lymphocytes will be experimentally infected with A. marginale and parameters of disease compared between depleted and non‐depleted calves.
Lymphocyte Stimulatory Capacity of Theileria annulata‐Infected Ovine Lymphoblastoid Cells
Authors: AHMED J. S. , DIEMER U. , VOSS‐HOLTMANN A. , SCHEIN E. , SCHNITTGER L.
Published: July 2010

Abstract: T. annulata, the causative agent of tropical theileriosis in cattle, is transmitted by ticks of the genus Hyalomma. Sporozoites of this parasite invade their target cells, where they differentiate to macroschizonts. T. annulata additionally invades and transforms ovine and caprine leukocytes. T. annulata infection in the ovine system is poorly studied, thus we used a mixed lymphocyte culture (MLC) to analyze the capacity of these cells to activate naïve uninfected ovine cells. The peak response was observed on day three or four and the response could not be induced by lysates of infected cells or their supernatants. The stimulated cells expressed IL‐2 and secreted an IL‐2‐like growth factor.
Tropical Bont Tick (Amblyomma variegatum) Eradication in the Caribbean: The St. Kitts Experience
Authors: PHILLIP KEITH ST. CLAIR
Published: July 2010

Abstract: The tropical bont tick (TBT) was first identified in St. Kitts in 1978. Initially, infestation was observed on cattle that developed a severe dermatitis. Over a period of seven years, the TBT spread to most areas of the island, affecting cattle, sheep, and goats. The ruminant livestock population declined from, 6,000, 9,000, and 7,000 cattle, sheep, and goats, respectively, in 1984 to an estimated 400, 800, and 1,000, cattle, sheep, and goats in 1990. A project to control the tropical bont tick on St. Kitts was implemented in 1983. This effort was based on the use of plunge dips located in communal grazing areas. In October of 1995, the Caribbean Amblyomma Programme was initiated on St. Kitts to eradicate the TBT from the Caribbean. In 1996, there were 416 animal owners with 2,000, 4,300, and 4,000 cattle, sheep, and goats, respectively. Cases of dermatophilosis, declined from 657 in 1995 to 153 in 1996. During the period 1997 to 1998 treatment with Flumethrin continued. The Department of Agriculture initiated activities for treatment compliance, monitoring, and TBT surveillance. The animal population increased to 3,000, 6,000, and 4,500 cattle, sheep, and goats, respectively, and with 810 animal owners participating. The number of cases of dermatophilosis declined to 42. In 1998, the TBT was confined to three foci. The remainder of the island was declared provisionally tick free.
At the End of the Day: The Socioeconomic Impacts of Eradicating Contagious Bovine Pleuropneumonia from Botswana
Authors: MULLINS GARY R. , FIDZANI BOGA , KOLANYANE METSEYABAGALE
Published: July 2010

Abstract: In February 1995, an outbreak of contagious bovine pleuropneumonia occurred in the Northwest district of Ngamiland, Botswana. The government of Botswana determined to eradicate the disease by depopulating the entire district of cattle. In total, 320,000 cattle were destroyed. Measures were put in place by government to mitigate the effects of eradication on the affected communities and household monitoring was instituted. This paper reports the major findings of the monitoring exercise. It is observed that although 45% of households said they would rely on arable cropping as a coping strategy, only 29% expected to produce sufficient food for themselves. Use of permanent, male agricultural labor fell by 33%, whereas both permanent and temporary female labor increased substantially. Although eight out of ten respondents planned to rebuild their herds, routine household demands on the generally small cash compensation received suggest that economic recovery for many of Ngamiland's households is likely to be prolonged. It is recommended that relief programmes continue but with improved targeting. Objective indicators are needed to determine when government assistance can be terminated.