ABSTRACT
OBJECTIVES: To describe the historical evolution and dissemination of the Oral Medicine and Oral and Maxillofacial Pathology international societies and associations across the globe, and to provide insights into their significant contributions toward oral health promotion. STUDY DESIGN: This review was conducted in accordance with the JBI Scoping Review Methodology Group guidance. The reporting followed the Preferred Reporting Items for Systematic Reviews extension for Scoping Reviews (PRISMA-ScR). RESULTS: Search strategy was applied to 5 databases (MEDLINE/PubMed, Scopus, Embase, Web of Science, Latin American and Caribbean Health Sciences (LILACS)) and grey literature (Google Scholar, Open Grey and ProQuest), as well as additional sources, such as organization websites. Eighty-nine sources were included in this review. Forty-six professional associations/societies were identified, of which 39 represented a country or geopolitical region, 2 represented continents, 2 represented multinational organizations and 3 multinational study groups. CONCLUSIONS: Documentation of the historical establishment and development of Oral Medicine and Oral and Maxillofacial Pathology organizations worldwide is limited and describing these processes remains challenging. Analysis of global data reveals heterogeneous development and distribution, resulting in disparities in accessibility and standardization. Further efforts toward oral health promotion should be implemented.
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OBJECTIVES: The authors aimed to evaluate whether blood cadmium (B-Cd), lead (B-Pb) and mercury (B-Hg) in children differ regionally in 9 countries, and to identify factors correlating with exposure. MATERIAL AND METHODS: The authors performed a cross-sectional study of children aged 7-14 years, living in 2007-2008 in urban, rural, or potentially polluted ("hot spot") areas (ca. 50 children from each area, in total 1363 children) in 6 European and 3 non-European countries. The authors analyzed Cd, Pb, and total Hg in blood and collected information on potential determinants of exposure through questionnaires. Regional differences in exposure levels were assessed within each country. RESULTS: Children living near industrial "hot-spots" had B-Cd 1.6 (95% CI: 1.4-1.9) times higher in the Czech Republic and 2.1 (95% CI:1.6-2.8) times higher in Poland, as compared to urban children in the same countries (geometric means [GM]: 0.13 µg/l and 0.15 µg/l, respectively). Correspondingly, B-Pb in the "hot spot" areas was 1.8 (95% CI: 1.6-2.1) times higher than in urban areas in Slovakia and 2.3 (95% CI: 1.9-2.7) times higher in Poland (urban GM: 19.4 µg/l and 16.3 µg/l, respectively). In China and Morocco, rural children had significantly lower B-Pb than urban ones (urban GM: 64 µg/l and 71 µg/l, respectively), suggesting urban exposure from leaded petrol, water pipes and/or coal-burning. Hg "hot spot" areas in China had B-Hg 3.1 (95% CI: 2.7-3.5) times higher, and Ecuador 1.5 (95% CI: 1.2-1.9) times higher, as compared to urban areas (urban GM: 2.45 µg/l and 3.23 µg/l, respectively). Besides industrial exposure, traffic correlated with B-Cd; male sex, environmental tobacco smoke, and offal consumption with B-Pb; and fish consumption and amalgam fillings with B-Hg. However, these correlations could only marginally explain regional differences. CONCLUSIONS: These mainly European results indicate that some children experience about doubled exposures to toxic elements just because of where they live. These exposures are unsafe, identifiable, and preventable and therefore call for preventive actions. Int J Occup Med Environ Health. 2023;36(3):349-64.
Subject(s)
Cadmium , Mercury , Male , Animals , Lead , Morocco/epidemiology , Cross-Sectional Studies , Ecuador , ChinaABSTRACT
Root hairs (RH) are excellent model systems for studying cell size and polarity since they elongate several hundred-fold their original size. Their tip growth is determined both by intrinsic and environmental signals. Although nutrient availability and temperature are key factors for a sustained plant growth, the molecular mechanisms underlying their sensing and downstream signaling pathways remain unclear. We use genetics to address the roles of the cell surface receptor kinase FERONIA (FER) and the nutrient sensing TOR Complex 1 (TORC) in RH growth. We identified that low temperature (10°C) triggers a strong RH elongation response in Arabidopsis thaliana involving FER and TORC. We found that FER is required to perceive limited nutrient availability caused by low temperature. FERONIA interacts with and activates TORC-downstream components to trigger RH growth. In addition, the small GTPase Rho of plants 2 (ROP2) is also involved in this RH growth response linking FER and TOR. We also found that limited nitrogen nutrient availability can mimic the RH growth response at 10°C in a NRT1.1-dependent manner. These results uncover a molecular mechanism by which a central hub composed by FER-ROP2-TORC is involved in the control of RH elongation under low temperature and nitrogen deficiency.
Subject(s)
Arabidopsis Proteins , Arabidopsis , Arabidopsis/metabolism , Nitrates/pharmacology , Nitrates/metabolism , Arabidopsis Proteins/metabolism , Temperature , Phosphotransferases/metabolism , Nitrogen/metabolism , Plant Roots/metabolism , Plant Proteins/metabolism , Anion Transport Proteins/metabolismABSTRACT
OBJECTIVE: To compare tooth movement rate and histological responses with three different force magnitude designs under osteoperforation in rabbit models. METHODOLOGY: 48 rabbits were divided into three groups: Group A, Group B, and Group C, with traction force of 50 g, 100 g, 150 g, respectively. Osteoperforation was performed at the mesial of the right mandibular first premolar, the left side was not affected. One mini-screw was inserted into bones between two central incisors. Coil springs were fixed to the first premolars and the mini-screw. Tooth movement distance was calculated, and immunohistochemical staining of PCNA, OCN, VEGF, and TGF-ß1 was analyzed. RESULTS: The tooth movement distance on the surgical side was larger than the control side in all groups (P<0.01). No significant intergroup difference was observed for the surgical side in tooth movement distance among the three groups (P>0.05). For the control side, tooth movement distance in Group A was significantly smaller than Groups B and C (P<0.001); no significant difference in tooth movement distance between Group B and Group C was observed (P>0.05). On the tension area of the moving premolar, labeling of PCNA, OCN, VEGF and TGF-ß1 were confirmed in alveolar bone and periodontal ligament in all groups. PCNA, OCN, VEGF and TGF-ß1 on the surgical side was larger than the control side in all groups (P<0.001). CONCLUSION: Osteoperforation could accelerate orthodontic tooth movement rate in rabbits. Fast osteoperforation-assisted tooth movement in rabbits was achieve with light 50 g traction.
Subject(s)
Periodontal Ligament , Tooth Movement Techniques , Animals , Bicuspid , RabbitsABSTRACT
Abstract Objective To compare tooth movement rate and histological responses with three different force magnitude designs under osteoperforation in rabbit models. Methodology 48 rabbits were divided into three groups: Group A, Group B, and Group C, with traction force of 50 g, 100 g, 150 g, respectively. Osteoperforation was performed at the mesial of the right mandibular first premolar, the left side was not affected. One mini-screw was inserted into bones between two central incisors. Coil springs were fixed to the first premolars and the mini-screw. Tooth movement distance was calculated, and immunohistochemical staining of PCNA, OCN, VEGF, and TGF-β1 was analyzed. Results The tooth movement distance on the surgical side was larger than the control side in all groups (P<0.01). No significant intergroup difference was observed for the surgical side in tooth movement distance among the three groups (P>0.05). For the control side, tooth movement distance in Group A was significantly smaller than Groups B and C (P<0.001); no significant difference in tooth movement distance between Group B and Group C was observed (P>0.05). On the tension area of the moving premolar, labeling of PCNA, OCN, VEGF and TGF-β1 were confirmed in alveolar bone and periodontal ligament in all groups. PCNA, OCN, VEGF and TGF-β1 on the surgical side was larger than the control side in all groups (P<0.001). Conclusion Osteoperforation could accelerate orthodontic tooth movement rate in rabbits. Fast osteoperforation-assisted tooth movement in rabbits was achieve with light 50 g traction.
Subject(s)
Animals , Periodontal Ligament , Tooth Movement Techniques , Rabbits , BicuspidABSTRACT
El lupus eritematoso sistémico (LES) es una enfermedad multisistémica con manifestaciones proteicas. La pancreatitis lúpica es la segunda enfermedad más frecuentemente asociada con el abdomen agudo en relación con el LES. Si bien la pancreatitis aguda es rara, es clínicamente importante porque puede ser potencialmente mortal si no se trata de inmediato. En este artículo, describimos el caso de una niña de 10 años que desarrolló pancreatitis asociada a LES después del tratamiento con corticoesteroides que se complicó posteriormente debido a septicemia fúngica. Los signos y síntomas clínicos mejoraron marcadamente después de la administración de glucocorticoides y ciclofosfamida.
Systemic lupus erythematosus (SLE) is a multisystem disease with protean manifestations. Lupus pancreatitis is the second most common disease associated with SLE-related acute abdomen. Although acute pancreatitis is rare it is clinically important because this condition can be life threatening if not treated promptly. Here, we report a case of a 10-year-old girl who developed SLE-associated pancreatitis after steroids therapy that was subsequently complicated by fungal septicaemia. Her clinical symptoms and signs markedly improved after administration of glucocorticoids and cyclophosphamide.
Subject(s)
Humans , Female , Child , Pancreatitis , Child , Sepsis , Lupus Erythematosus, Systemic , MycosesABSTRACT
Systemic lupus erythematosus (SLE) is a multisystem disease with protean manifestations. Lupus pancreatitis is the second most common disease associated with SLE-related acute abdomen. Although acute pancreatitis is rare it is clinically important because this condition can be life threatening if not treated promptly. Here, we report a case of a 10-year-old girl who developed SLE-associated pancreatitis after steroids therapy that was subsequently complicated by fungal septicaemia. Her clinical symptoms and signs markedly improved after administration of glucocorticoids and cyclophosphamide.
El lupus eritematoso sistémico (LES) es una enfermedad multisistémica con manifestaciones proteicas. La pancreatitis lúpica es la segunda enfermedad más frecuentemente asociada con el abdomen agudo en relación con el LES. Si bien la pancreatitis aguda es rara, es clínicamente importante porque puede ser potencialmente mortal si no se trata de inmediato. En este artículo, describimos el caso de una niña de 10 años que desarrolló pancreatitis asociada a LES después del tratamiento con corticoesteroides que se complicó posteriormente debido a septicemia fúngica. Los signos y síntomas clínicos mejoraron marcadamente después de la administración de glucocorticoides y ciclofosfamida.
Subject(s)
Cyclophosphamide/administration & dosage , Glucocorticoids/administration & dosage , Lupus Erythematosus, Systemic/complications , Pancreatitis/etiology , Acute Disease , Child , Female , Fungemia/diagnosis , Humans , Immunosuppressive Agents/administration & dosage , Lupus Erythematosus, Systemic/drug therapy , Pancreatitis/diagnosisABSTRACT
Pituitary adenoma is one of the most common tumors in the neuroendocrine system. This study investigated the effects of long non-coding RNAs (lncRNAs) highly up-regulated in liver cancer (HULC) on rat secreting pituitary adenoma GH3 cell viability, migration, invasion, apoptosis, and hormone secretion, as well as the underlying potential mechanisms. Cell transfection and qRT-PCR were used to change and measure the expression levels of HULC, miR-130b, and FOXM1. Cell viability, migration, invasion, and apoptosis were assessed using trypan blue staining assay, MTT assay, two-chamber transwell assay, Guava Nexin assay, and western blotting. The concentrations of prolactin (PRL) and growth hormone (GH) in culture supernatant of GH3 cells were assessed using ELISA. The targeting relationship between miR-130b and FOXM1 was verified using dual luciferase activity. Finally, the expression levels of key factors involved in PI3K/AKT/mTOR and JAK1/STAT3 pathways were evaluated using western blotting. We found that HULC was highly expressed in GH3 cells. Overexpression of HULC promoted GH3 cell viability, migration, invasion, PRL and GH secretion, as well as activated PI3K/AKT/mTOR and JAK1/STAT3 pathways. Knockdown of HULC had opposite effects and induced cell apoptosis. HULC negatively regulated the expression of miR-130b, and miR-130b participated in the effects of HULC on GH3 cells. FOXM1 was a target gene of miR-130b, which was involved in the regulation of GH3 cell viability, migration, invasion, and apoptosis, as well as PI3K/AKT/mTOR and JAK1/STAT3 pathways. In conclusion, HULC tumor-promoting roles in secreting pituitary adenoma might be via down-regulating miR-130b, up-regulating FOXM1, and activating PI3K/AKT/mTOR and JAK1/STAT3 pathways.
Subject(s)
Adenoma/pathology , Pituitary Neoplasms/pathology , RNA, Long Noncoding/physiology , Adenoma/genetics , Adenoma/metabolism , Animals , Apoptosis/physiology , Blotting, Western , Cell Line, Tumor , Cell Migration Assays , Cell Movement/physiology , Cell Survival/physiology , Enzyme-Linked Immunosorbent Assay , Forkhead Box Protein M1/analysis , Forkhead Box Protein M1/metabolism , Humans , Janus Kinase 1/analysis , Janus Kinase 1/metabolism , Luciferases , MicroRNAs/analysis , MicroRNAs/metabolism , Phosphatidylinositol 3-Kinases/analysis , Phosphatidylinositol 3-Kinases/metabolism , Pituitary Neoplasms/genetics , Pituitary Neoplasms/metabolism , Proto-Oncogene Proteins c-akt/analysis , Proto-Oncogene Proteins c-akt/metabolism , RNA, Long Noncoding/analysis , Rats , Reverse Transcriptase Polymerase Chain Reaction , STAT3 Transcription Factor/analysis , STAT3 Transcription Factor/metabolism , TOR Serine-Threonine Kinases/analysis , TOR Serine-Threonine Kinases/metabolism , TransfectionABSTRACT
Pituitary adenoma is one of the most common tumors in the neuroendocrine system. This study investigated the effects of long non-coding RNAs (lncRNAs) highly up-regulated in liver cancer (HULC) on rat secreting pituitary adenoma GH3 cell viability, migration, invasion, apoptosis, and hormone secretion, as well as the underlying potential mechanisms. Cell transfection and qRT-PCR were used to change and measure the expression levels of HULC, miR-130b, and FOXM1. Cell viability, migration, invasion, and apoptosis were assessed using trypan blue staining assay, MTT assay, two-chamber transwell assay, Guava Nexin assay, and western blotting. The concentrations of prolactin (PRL) and growth hormone (GH) in culture supernatant of GH3 cells were assessed using ELISA. The targeting relationship between miR-130b and FOXM1 was verified using dual luciferase activity. Finally, the expression levels of key factors involved in PI3K/AKT/mTOR and JAK1/STAT3 pathways were evaluated using western blotting. We found that HULC was highly expressed in GH3 cells. Overexpression of HULC promoted GH3 cell viability, migration, invasion, PRL and GH secretion, as well as activated PI3K/AKT/mTOR and JAK1/STAT3 pathways. Knockdown of HULC had opposite effects and induced cell apoptosis. HULC negatively regulated the expression of miR-130b, and miR-130b participated in the effects of HULC on GH3 cells. FOXM1 was a target gene of miR-130b, which was involved in the regulation of GH3 cell viability, migration, invasion, and apoptosis, as well as PI3K/AKT/mTOR and JAK1/STAT3 pathways. In conclusion, HULC tumor-promoting roles in secreting pituitary adenoma might be via down-regulating miR-130b, up-regulating FOXM1, and activating PI3K/AKT/mTOR and JAK1/STAT3 pathways.
Subject(s)
Humans , Animals , Rats , Pituitary Neoplasms/pathology , Adenoma/pathology , RNA, Long Noncoding/physiology , Enzyme-Linked Immunosorbent Assay , Transfection , Adenoma/genetics , Adenoma/metabolism , Cell Movement/physiology , Cell Survival/physiology , Blotting, Western , Apoptosis/physiology , MicroRNAs/analysis , Cell Line, Tumor , STAT3 Transcription Factor/analysis , Janus Kinase 1/analysis , Janus Kinase 1/metabolism , Cell Migration Assays , Forkhead Box Protein M1/analysis , Forkhead Box Protein M1/metabolism , LuciferasesABSTRACT
Compounds featuring weakly-coordinating N-oxides or carbonyl groups, as for instance, quinoline N-oxide and quinonoid systems represent important structural scaffolds with potential biological activities. Due to their biological importance, significant efforts have been devoted to devise robust methods for their step-economical preparation. Among these approaches, the C-H activation strategy has emerged as a powerful, versatile and efficient tool in molecular sciences. This feature article summarizes recent key advances in transition-metal-catalyzed C-H functionalization for A-ring functionalization of heterocyclic and quinoidal compounds by challenging weakly-coordinating entities, published prior to May 2018.
ABSTRACT
En este artículo, presentamos el caso de una paciente con glomerulonefritis aguda postestreptocócica (GNAPE) y anemia hemolítica autoinmunitaria (AHAI). Además de los signos típicos de la GNAPE, la paciente tuvo un resultado positivo en la prueba de antiglobulina directa y anticuerpos contra la cardiolipina sin que presentara las manifestaciones clínicas típicas del síndrome antifosfolipídico. Este caso genera dudas respecto de la relación entre el estreptococo y el desarrollo de anemia hemolítica autoinmunitaria en los niños. Este caso destaca la posibilidad de que las infecciones estreptocócicas de nuestra paciente podrían haber causado la anemia, ya sea en el contexto de anticuerpos antifosfolipídicos preexistentes o por haber desencadenado el desarrollo de anticuerpos patogénicos, que luego lleva a la presentación clínica de hemólisis. Se presume que, en la paciente, los anticuerpos contra la cardiolipina inducidos por la infección estreptocócica podrían tener una función directa en la presentación clínica de AHAI.
We present a case of acute post-streptococcal glomerulonephritis (APSGN) with autoimmune hemolytic anemia (AIHA). Along with the classic findings of APSGN, the patient had a positive direct antiglobulin test and an anticardiolipin antibody without any typical clinical manifestations of antiphospholipid syndrome (APS). This case raises questions of the relationship between Streptococcus and the development of autoimmune hemolytic anemia in children. Our case highlights the possibility that the streptococcal infections in this patient might be responsible for her anemia, either in setting of underlying antiphospholipid antibodies, or in having triggered the development of pathogenic antibodies, which subsequently leads to the clinical evolution of hemolysis. It is presumed that in our case, the anticardiolipin antibody induced by streptococcal infection may play a direct role in the clinical evolution of AIHA.
Subject(s)
Humans , Female , Child , Antibodies, Anticardiolipin/blood , Glomerulonephritis/blood , Anemia, Hemolytic, Autoimmune/blood , Streptococcal Infections/complications , Glomerulonephritis/microbiology , Anemia, Hemolytic, Autoimmune/complicationsABSTRACT
We present a case of acute post-streptococcal glomerulonephritis (APSGN) with autoimmune hemolytic anemia (AIHA). Along with the classic findings of APSGN, the patient had a positive direct antiglobulin test and an anticardiolipin antibody without any typical clinical manifestations of antiphospholipid syndrome (APS). This case raises questions of the relationship between Streptococcus and the development of autoimmune hemolytic anemia in children. Our case highlights the possibility that the streptococcal infections in this patient might be responsible for her anemia, either in setting of underlying antiphospholipid antibodies, or in having triggered the development of pathogenic antibodies, which subsequently leads to the clinical evolution of hemolysis. It is presumed that in our case, the anticardiolipin antibody induced by streptococcal infection may play a direct role in the clinical evolution of AIHA.
En este artículo, presentamos el caso de una paciente con glomerulonefritis aguda postestreptocócica (GNAPE) y anemia hemolítica autoinmunitaria (AHAI). Además de los signos típicos de la GNAPE, la paciente tuvo un resultado positivo en la prueba de antiglobulina directa y anticuerpos contra la cardiolipina sin que presentara las manifestaciones clínicas típicas del síndrome antifosfolipídico. Este caso genera dudas respecto de la relación entre el estreptococo y el desarrollo de anemia hemolítica autoinmunitaria en los niños. Este caso destaca la posibilidad de que las infecciones estreptocócicas de nuestra paciente podrían haber causado la anemia, ya sea en el contexto de anticuerpos antifosfolipídicos preexistentes o por haber desencadenado el desarrollo de anticuerpos patogénicos, que luego lleva a la presentación clínica de hemólisis. Se presume que, en la paciente, los anticuerpos contra la cardiolipina inducidos por la infección estreptocócica podrían tener una función directa en la presentación clínica de AHAI.
Subject(s)
Anemia, Hemolytic, Autoimmune/blood , Antibodies, Anticardiolipin/blood , Glomerulonephritis/blood , Anemia, Hemolytic, Autoimmune/complications , Child , Female , Glomerulonephritis/microbiology , Humans , Streptococcal Infections/complicationsABSTRACT
The biomineralisation of metal phosphates is a promising approach to develop more efficient nanobiocatalysts; however, the interactions between the protein and the inorganic mineral are poorly understood. Elucidating which protein regions most likely participate in the mineral formation will guide the fabrication of more efficient biocatalysts based on metal-phosphate nanoflowers. We have biomineralised the lipase from Thermomyces lanuginosus using three calcium, zinc and copper phosphates to fabricate different types of bio-inorganic nanoflowers. To better understand how the biomineralisation process affects the enzyme properties, we have computationally predicted the protein regions with a higher propensity for binding Ca2+, Cu2+ and Zn2+. These binding sites can be considered as presumable nucleation points where the biomineralisation process starts and explain why different metals can form bio-inorganic nanoflowers of the same enzyme with different functional properties. The formation of calcium, copper and zinc phosphates in the presence of this lipase gives rise to nanoflowers with different morphologies and different enzymatic properties such as activity, stability, hyperactivation and activity-pH profile; these functional differences are supported by structural studies based on fluorescence spectroscopy and can be explained by the different locations of the predicted nucleation sites for the different metals. Among the three metals used herein, the mineralisation of this lipase with zinc-phosphate enables the fabrication of bio-inorganic nanoflowers 34 times more stable than the soluble enzyme. These bio-inorganic nanoflowers were reused for 8 reaction cycles achieving 100% yield in the hydrolysis of p-nitrophenol butyrate but losing more than 50% of their initial activity after 6 operational cycles. Finally, this heterogeneous biocatalyst was more active and enantioselective than the soluble enzyme (ee = 79%(R)) towards the kinetic resolution of rac-1-phenylethyl acetate yielding the R enantiomer with ee = 84%.
ABSTRACT
OBJECTIVES: Fixed-dose combination formulations, which simplify the administration of drugs and prevent the development of drug resistance, have been recommended as a standard anti-tuberculosis treatment regimen. However, the composition and dosage recommendations for fixed-dose combination formulations differ from those for separate formulations. Thus, questions about the effectiveness and side effects of combination formulations remain. The aim of this study was to compare the safety and efficacy of these two types of anti-tuberculosis regimens for pulmonary tuberculosis treatment. METHOD: A prospective, randomized controlled study was conducted using the directly observed treatment short-course strategy. Patients were randomly allocated to one of two short-course regimens. One year after completing the treatment, these patients' outcomes were analyzed. ClinicalTrials.gov: NCT00979290. RESULTS: A total of 161 patients were enrolled, 142 of whom were evaluable for safety assessment. The two regimens had a similar incidence of adverse effects. In the per-protocol population, serum bilirubin concentrations at the peak level, at week 4, and at week 8 were significantly higher for the fixed-dose combination formulation than for the separate formulations. All patients had negative sputum cultures at the end of the treatment, and no relapse occurred after one year of follow-up. CONCLUSIONS: In this randomized study, transient higher serum bilirubin levels were noted for the fixed-dose combination regimen compared with the separate formulations during treatment. However, no significant difference in safety or efficacy was found between the groups when the directly observed treatment short-course strategy was used.
Subject(s)
Antitubercular Agents/administration & dosage , Tuberculosis, Pulmonary/drug therapy , Adult , Aged , Aged, 80 and over , Antitubercular Agents/adverse effects , Bilirubin/blood , Directly Observed Therapy/methods , Drug Administration Schedule , Drug Combinations , Drug Therapy, Combination/adverse effects , Drug Therapy, Combination/methods , Female , Follow-Up Studies , Humans , Hyperuricemia/chemically induced , Male , Middle Aged , Prospective Studies , Radiography , Skin Diseases/chemically induced , Sputum/microbiology , Treatment Outcome , Tuberculosis, Pulmonary/diagnostic imaging , Vision Disorders/chemically inducedABSTRACT
OBJECTIVES: Fixed-dose combination formulations, which simplify the administration of drugs and prevent the development of drug resistance, have been recommended as a standard anti-tuberculosis treatment regimen. However, the composition and dosage recommendations for fixed-dose combination formulations differ from those for separate formulations. Thus, questions about the effectiveness and side effects of combination formulations remain. The aim of this study was to compare the safety and efficacy of these two types of anti-tuberculosis regimens for pulmonary tuberculosis treatment. METHOD: A prospective, randomized controlled study was conducted using the directly observed treatment short-course strategy. Patients were randomly allocated to one of two short-course regimens. One year after completing the treatment, these patients’ outcomes were analyzed. ClinicalTrials.gov: NCT00979290. RESULTS: A total of 161 patients were enrolled, 142 of whom were evaluable for safety assessment. The two regimens had a similar incidence of adverse effects. In the per-protocol population, serum bilirubin concentrations at the peak level, at week 4, and at week 8 were significantly higher for the fixed-dose combination formulation than for the separate formulations. All patients had negative sputum cultures at the end of the treatment, and no relapse occurred after one year of follow-up. CONCLUSIONS: In this randomized study, transient higher serum bilirubin levels were noted for the fixed-dose combination regimen compared with the separate formulations during treatment. However, no significant difference in safety or efficacy was found between the groups when the directly observed treatment short-course strategy was used. .
Subject(s)
Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Antitubercular Agents/administration & dosage , Tuberculosis, Pulmonary/drug therapy , Antitubercular Agents/adverse effects , Bilirubin/blood , Drug Administration Schedule , Drug Combinations , Directly Observed Therapy/methods , Drug Therapy, Combination/adverse effects , Drug Therapy, Combination/methods , Follow-Up Studies , Hyperuricemia/chemically induced , Prospective Studies , Skin Diseases/chemically induced , Sputum/microbiology , Treatment Outcome , Tuberculosis, Pulmonary , Vision Disorders/chemically inducedABSTRACT
OBJECTIVES: The aim of the study was to make an international comparison of blood levels of cadmium (B-Cd), lead (B-Pb) and mercury (B-Hg) of women in seven European, and three non-European cities, and to identify determinants. MATERIALS AND METHODS: About 50 women (age: 46-62) from each city were recruited (totally 480) in 2006-2009. Interview and questionnaire data were obtained. Blood samples were analysed in one laboratory to avoid interlaboratory variation. RESULTS: Between the European cities, the B-Pb and B-Cd results vary little (range of geometric means: 13.5-27.0 µg/l and 0.25-0.65 µg/l, respectively); the variation of B-Hg was larger (0.40-1.38 µg/l). Between the non-European cities the results for B-Pb, B-Cd and B-Hg were 19.2-68.0, 0.39-0.99 and 1.01-2.73 µg/l, respectively. Smoking was a statistically significant determinant for B-Cd, while fish and shellfish intakes contributed to B-Hg and B-Pb, amalgam fillings also contributed to B-Hg. CONCLUSIONS: The present results confirm the previous results from children; the exposure to lead and cadmium varies only little between different European cities suggesting that other factors than the living area are more important. The study also confirms the previous findings of higher cadmium and lead levels in some non-European cities. The geographical variation for mercury is significant.
Subject(s)
Cadmium/blood , Environmental Illness/blood , Lead/blood , Mercury/blood , Urban Population , Women's Health , Croatia/epidemiology , Czech Republic/epidemiology , Ecuador/epidemiology , Environmental Exposure/analysis , Environmental Illness/epidemiology , Female , Humans , Incidence , Middle Aged , Morocco/epidemiology , Poland/epidemiology , Slovakia/epidemiology , Slovenia/epidemiology , Sweden/epidemiologyABSTRACT
OBJECTIVE: Epstein-Barr virus (EBV) is a ubiquitous human γ-herpes virus, which can adapt and evade host immune defense. Dendritic cells (DCs) play a pivotal role in the initiation and maintenance of immune responses. This study investigated the effects of EBV on cord blood monocytes derived DCs (CBDC). METHODS: Monocytes were isolated from cord blood and cultured in medium containing recombinant IL-4 and GM-CSF to induce DCs development. B95-8 supernatant was added in monocytes culture medium for EBV infection at day 0. Phenotypic characterization of DCs, apoptotic cells, and mitochondrial membrane potential (MMP) were detected by flow cytometry. The morphology was observed by Hoechst 33258 staining and TUNEL staining, the expression of X-linked inhibitor of apoptosis protein (XIAP) was detected by Western blotting assay and caspase 3, 8 and 9 activity was measured. RESULTS: Phenotypic characterization of DCs was changed in EBV-treated group. Chromatin condensation and DNA fragmentation were observed in EBV induced CBDC apoptosis. In addition, caspase 3, caspase 8, and caspase 9 activation were enhanced in the EBV-treated group. This was accompanied by the loss of MMP. Furthermore, XIAP expression was down-regulated in the EBV-treated group and compared to mock-infected group. CONCLUSION: These results suggested that EBV could inhibit CBDC phenotypic differentiation, and induce CBDC apoptosis in caspase-dependent manner with involvement of the mitochondrial pathway. This might help EBV to evade host immune responses to establish persistent infection.
Subject(s)
Apoptosis/physiology , Cytopathogenic Effect, Viral/physiology , Dendritic Cells/pathology , Fetal Blood/cytology , Herpesvirus 4, Human/physiology , Monocytes/pathology , Blotting, Western , Caspases/immunology , Cell Differentiation , Dendritic Cells/virology , Flow Cytometry , Herpesvirus 4, Human/immunology , Humans , Interleukin-4/immunology , Monocytes/cytology , Monocytes/virology , Phenotype , X-Linked Inhibitor of Apoptosis Protein/immunologyABSTRACT
OBJECTIVE: Epstein-Barr virus (EBV) is a ubiquitous human γ-herpes virus, which can adapt and evade host immune defense. Dendritic cells (DCs) play a pivotal role in the initiation and maintenance of immune responses. This study investigated the effects of EBV on cord blood monocytes derived DCs (CBDC). METHODS: Monocytes were isolated from cord blood and cultured in medium containing recombinant IL-4 and GM-CSF to induce DCs development. B95-8 supernatant was added in monocytes culture medium for EBV infection at day 0. Phenotypic characterization of DCs, apoptotic cells, and mitochondrial membrane potential (MMP) were detected by flow cytometry. The morphology was observed by Hoechst 33258 staining and TUNEL staining, the expression of X-linked inhibitor of apoptosis protein (XIAP) was detected by Western blotting assay and caspase 3, 8 and 9 activity was measured. RESULTS: Phenotypic characterization of DCs was changed in EBV-treated group. Chromatin condensation and DNA fragmentation were observed in EBV induced CBDC apoptosis. In addition, caspase 3, caspase 8, and caspase 9 activation were enhanced in the EBV-treated group. This was accompanied by the loss of MMP. Furthermore, XIAP expression was down-regulated in the EBV-treated group and compared to mock-infected group. CONCLUSION: These results suggested that EBV could inhibit CBDC phenotypic differentiation, and induce CBDC apoptosis in caspase-dependent manner with involvement of the mitochondrial pathway. This might help EBV to evade host immune responses to establish persistent infection.
Subject(s)
Humans , Apoptosis/physiology , Cytopathogenic Effect, Viral/physiology , Dendritic Cells/pathology , Fetal Blood/cytology , /physiology , Monocytes/pathology , Blotting, Western , Cell Differentiation , Caspases/immunology , Dendritic Cells/virology , Flow Cytometry , /immunology , /immunology , Monocytes/cytology , Monocytes/virology , Phenotype , X-Linked Inhibitor of Apoptosis Protein/immunologyABSTRACT
Children's blood-lead concentration (B-Pb) is well studied, but little is known about cadmium (B-Cd) and mercury (B-Hg), in particular for central Europe. Such information is necessary for risk assessment and management. Therefore, we here describe and compare B-Pb, B-Cd and B-Hg in children in six European, and three non-European cities, and identify determinants of these exposures. About 50 school children (7-14 years) from each city were recruited (totally 433) in 2007-2008. Interview and questionnaire data were obtained. A blood sample was analyzed: only two laboratories with strict quality control were used. The European cities showed only minor differences for B-Cd (geometric means 0.11-0.17 µg/L) and B-Pb (14-20 µg/L), but larger for B-Hg (0.12-0.94 µg/L). Corresponding means for the non-European countries were 0.21-0.26, 32-71, and 0.3-3.2 µg/L, respectively. For B-Cd in European samples, traffic intensity close to home was a statistically significant determinant, for B-Hg fish consumption and amalgam fillings, and for B-Pb sex (boys higher). This study shows that European city children's B-Cd and B-Pb vary only little between countries; B-Hg differs considerably, due to varying tooth restoration practices and fish intake. Traffic intensity seemed to be a determinant for B-Cd. The metal concentrations were low from a risk perspective but the chosen non-European cities showed higher concentrations than the cities in Europe.