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1.
BMC Geriatr ; 22(1): 663, 2022 08 12.
Article in English | MEDLINE | ID: mdl-35962346

ABSTRACT

BACKGROUND: We have looked at antimony (Sb) as a new neurotoxin which causes neuronal apoptosis in animal studies. At the population level, however, there is no direct evidence for a relationship between Sb exposure and cognitive performance. METHOD: The study comprehensively assessed the correlation between urinary antimony levels and cognitive test scores in 631 creatinine-corrected older persons using data from the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2014. RESULTS: Using logistic regression, the study looked at the prevalence of cognitive impairment at different levels of urine antimony concentrations and found that, after controlling for covariates, higher doses of urinary antimony were positively associated with cognitive function compared to controls, odds ratio (ORs) with 95% confidence interval (CI) were 0.409 (0.185-0.906) and 0.402 (0.186-0.871) respectively. Restricted cubic spline curves showed a non-linear and dose-specific correlation between urinary antimony and cognitive performance, with lower doses associated with better cognitive performance, while higher doses may be associated with cognitive impairment. CONCLUSIONS: Our data provide evidence for a correlation between Sb and cognitive function at the population level, although the specific mechanisms need to be investigated further.


Subject(s)
Antimony , Cognition , Antimony/adverse effects , Antimony/urine , Humans , Neuropsychological Tests , Nutrition Surveys , Odds Ratio
2.
Arterioscler Thromb Vasc Biol ; 42(1): 87-99, 2022 01.
Article in English | MEDLINE | ID: mdl-34879710

ABSTRACT

OBJECTIVE: Studies evaluating the association of metals with subclinical atherosclerosis are mostly limited to carotid arteries. We assessed individual and joint associations of nonessential metals exposure with subclinical atherosclerosis in 3 vascular territories. Approach and Results: One thousand eight hundred seventy-three Aragon Workers Health Study participants had urinary determinations of inorganic arsenic species, barium, cadmium, chromium, antimony, titanium, uranium, vanadium, and tungsten. Plaque presence in carotid and femoral arteries was determined by ultrasound. Coronary Agatston calcium score ≥1 was determined by computed tomography scan. Median arsenic, barium, cadmium, chromium, antimony, titanium, uranium, vanadium, and tungsten levels were 1.83, 1.98, 0.27, 1.18, 0.05, 9.8, 0.03, 0.66, and 0.23 µg/g creatinine, respectively. The adjusted odds ratio (95% CI) for subclinical atherosclerosis presence in at least one territory was 1.25 (1.03-1.51) for arsenic, 1.67 (1.22-2.29) for cadmium, and 1.26 (1.04-1.52) for titanium. These associations were driven by arsenic and cadmium in carotid, cadmium and titanium in femoral, and titanium in coronary territories and mostly remained after additional adjustment for the other relevant metals. Titanium, cadmium, and antimony also showed positive associations with alternative definitions of increased coronary calcium. Bayesian Kernel Machine Regression analysis simultaneously evaluating metal associations suggested an interaction between arsenic and the joint cadmium-titanium exposure. CONCLUSIONS: Our results support arsenic and cadmium and identify titanium and potentially antimony as atherosclerosis risk factors. Exposure reduction and mitigation interventions of these metals may decrease cardiovascular risk in individuals without clinical disease.


Subject(s)
Atherosclerosis/chemically induced , Carotid Artery Diseases/chemically induced , Coronary Artery Disease/chemically induced , Femoral Artery/drug effects , Metals/adverse effects , Occupational Exposure/adverse effects , Occupational Health , Adult , Antimony/adverse effects , Antimony/urine , Arsenic/adverse effects , Arsenic/urine , Asymptomatic Diseases , Atherosclerosis/diagnostic imaging , Atherosclerosis/epidemiology , Atherosclerosis/urine , Biomarkers/urine , Cadmium/adverse effects , Cadmium/urine , Carotid Artery Diseases/diagnostic imaging , Carotid Artery Diseases/epidemiology , Carotid Artery Diseases/urine , Coronary Artery Disease/diagnostic imaging , Coronary Artery Disease/epidemiology , Coronary Artery Disease/urine , Cross-Sectional Studies , Female , Femoral Artery/diagnostic imaging , Humans , Male , Metals/urine , Middle Aged , Plaque, Atherosclerotic , Risk Assessment , Risk Factors , Spain/epidemiology , Titanium/adverse effects , Titanium/urine
3.
Pharmacol Biochem Behav ; 212: 173313, 2022 01.
Article in English | MEDLINE | ID: mdl-34896416

ABSTRACT

Environmental factors have been associated with the etiology of autism spectrum disorder ASD in recent times. The involvement of toxic metals in the generation of reactive oxygen species and their epigenetics effects have been implicated in ASD. This systemic review examines the association of toxic metals with autism in children. A systematic literature search was performed in scientific databases such as PubMed, Google scholar, and Scopus. Case-control studies evaluating toxic metal levels in different tissues of ASD children and comparing them to healthy children (control group) were identified. The Newcastle-Ottawa Scale was used to evaluate the risk of bias of the included studies. Six case-control studies with 425 study subjects met our inclusion criteria. A total of four studies indicated higher levels of As, Pb, Hg, Cd, Al, Sn, Sb, Ba, TI, W, and Zr in whole blood, RBC, in whole blood, RBC, and hair samples of children with autism compared with control suggestive of a greater toxic metal exposure (immediate and long-term). Three studies identified significantly higher concentrations of Cd, Pb and Hg in urine and hair samples of autistic children compared to control suggesting decreased excretion and possible high body burden of these metals. The findings from this review demonstrate that high levels of toxic metals are associated with ASD, therefore, critical care is necessary to reduce body burden of these metals in children with ASD as a major therapeutic strategy.


Subject(s)
Autism Spectrum Disorder/chemically induced , Metals/adverse effects , Aluminum/adverse effects , Antimony/adverse effects , Arsenic/adverse effects , Autism Spectrum Disorder/blood , Autism Spectrum Disorder/urine , Cadmium/adverse effects , Case-Control Studies , Child , Child, Preschool , Female , Humans , Lead/adverse effects , Male , Mercury/adverse effects , Public Health , Reactive Oxygen Species , Tin/adverse effects , Titanium/adverse effects , Zirconium/adverse effects
4.
J Med Entomol ; 58(6): 2130-2137, 2021 11 09.
Article in English | MEDLINE | ID: mdl-34230971

ABSTRACT

The present study aimed to investigate the impact of gunshot residue (GSR) components (Pb, Sb, and Ba) on the life history parameters of Lucilia sericata (Meigen, 1826) (Diptera: Calliphoridae). This experiment was carried out at the Zoology Department, the Ondokuz Mayis University in 2020. About 50 larvae, respectively were exposed to the chicken liver with four different concentrations of GSR particles and life history parameters recorded. A two-way analysis of variance (Two way ANOVA) was used on the larval weight, and length, development time, percentage of pupal and larval survival. Pearson's correlation coefficient was used to assess the association between life-history parameters and the concentration of GSR. The total development times decreased with increasing Sb, Ba, and Pb concentrations in the diets 1-3 d when compared to the control The results showed that Ba and Sb significantly decreased larval and pupal survival and GSR decreased the pupa and adult weight as compared to the control. We concluded that life-history parameters of L. sericata are sensitive to GSR residue and heavy metal changes in the environment. The presence of gunshot residue in the corpse should be kept in mind in a criminal investigation.


Subject(s)
Calliphoridae/growth & development , Life History Traits , Animals , Antimony/adverse effects , Barium/adverse effects , Calliphoridae/drug effects , Diet , Forensic Entomology , Larva/drug effects , Larva/growth & development , Lead/adverse effects , Pupa/drug effects , Pupa/growth & development
5.
Ecotoxicol Environ Saf ; 220: 112339, 2021 Sep 01.
Article in English | MEDLINE | ID: mdl-34015637

ABSTRACT

To clarify the response mechanism of paddy soil microorganisms to contamination caused by antimony (Sb) alone, we added K(SbO)C4H4O6.1/2 H2O with different contents to uncontaminated paddy soil and carried out related studies. 16S rRNA was sequenced in V3-V4 regions of paddy soil bacteria with different Sb contamination levels. Then, α diversity and species enrichment and separation of paddy soil microorganisms were analyzed. The biochemical behavior and the influences of Sb fractions on bacterial communities and ecological function were explored in paddy soil with different contamination levels. The results showed that the contents of Sbtot and Sb(V) increased with the increase of contamination level, and the difference was significant among the groups. For Sbexe and Sbsrp there were slight differences between S100 and S200 groups, but significant differences among other groups. The diversity index increased with the increase of Sb concentration, which reached the maximum value in S200 group and the minimum value in control group (SC). The relative importance analysis demonstrated that Sb(III) and Sbsrp were the main Sb fractions affecting the diversity index of bacterial community. In addition, the results of principal coordinate analysis (PCoA) showed that there were significant differences between the bacterial communities in SC and in the soil with different Sb contamination levels. Based on diversity analysis, it was found that Proteobacteria, Actinobacteria and Bacteroidetes were the main dominant phyla in paddy soil with different Sb concentrations, and their enrichment and separation were greater than those of other dominant phyla. Though the Static Bayesian network inference, it was shown that Sbtot affected Sphingomonadaceae, and Sbsrp affected Burkholderiaceae, Xanthomonadaceae and Acidobacteriale to further affect bacterial communities, while Sb(V) mainly affected Flavobacteriaceae, Rhodopirillaceae and Acidobacteriale. The above results provide a scientific basis for the biochemical restoration potential of paddy soils with different Sb contamination levels.


Subject(s)
Antimony/adverse effects , Bacteria/drug effects , Bacterial Physiological Phenomena/drug effects , Microbiota/drug effects , Soil Microbiology , Soil Pollutants/adverse effects , China
6.
PLoS Negl Trop Dis ; 15(3): e0009302, 2021 03.
Article in English | MEDLINE | ID: mdl-33780461

ABSTRACT

BACKGROUND: Despite a historical association with poor tolerability, a comprehensive review on safety of antileishmanial chemotherapies is lacking. We carried out an update of a previous systematic review of all published clinical trials in visceral leishmaniasis (VL) from 1980 to 2019 to document any reported serious adverse events (SAEs). METHODS: For this updated systematic review, we searched the following databases from 1st Jan 2016 through 2nd of May 2019: PUBMED, Embase, Scopus, Web of Science, Cochrane, clinicaltrials.gov, WHO ICTRP, and the Global Index Medicus. We included randomised and non-randomised interventional studies aimed at assessing therapeutic efficacy and extracted the number of SAEs reported within the first 30 days of treatment initiation. The incidence rate of death (IRD) from individual treatment arms were combined in a meta-analysis using random effects Poisson regression. RESULTS: We identified 157 published studies enrolling 35,376 patients in 347 treatment arms. Pentavalent antimony was administered in 74 (21.3%), multiple-dose liposomal amphotericin B (L-AmB) in 52 (15.0%), amphotericin b deoxycholate in 51 (14.7%), miltefosine in 33 (9.5%), amphotericin b fat/lipid/colloid/cholesterol in 31 (8.9%), and single-dose L-AmB in 17 (4.9%) arms. There was a total of 804 SAEs reported of which 793 (including 428 deaths) were extracted at study arm level (11 SAEs were reported at study level only). During the first 30 days, there were 285 (66.6%) deaths with the overall IRD estimated at 0.068 [95% confidence interval (CI): 0.041-0.114; I2 = 81.4%; 95% prediction interval (PI): 0.001-2.779] per 1,000 person-days at risk; the rate was 0.628 [95% CI: 0.368-1.021; I2 = 82.5%] in Eastern Africa, and 0.041 [95% CI: 0.021-0.081; I2 = 68.1%] in the Indian Subcontinent. In 21 study arms which clearly indicated allowing the inclusion of patients with HIV co-infections the IRD was 0.575 [95% CI: 0.244-1.355; I2 = 91.9%] compared to 0.043 [95% CI: 0.020-0.090; I2 = 62.5%] in 160 arms which excluded HIV co-infections. CONCLUSION: Mortality within the first 30 days of VL treatment initiation was a rarely reported event in clinical trials with an overall estimated rate of 0.068 deaths per 1,000 person-days at risk, though it varied across regions and patient populations. These estimates may serve as a benchmark for future trials against which mortality data from prospective and pharmacovigilance studies can be compared. The methodological limitations exposed by our review support the need to assemble individual patient data (IPD) to conduct robust IPD meta-analyses and generate stronger evidence from existing trials to support treatment guidelines and guide future research.


Subject(s)
Antiprotozoal Agents/adverse effects , Antiprotozoal Agents/therapeutic use , Leishmaniasis, Visceral/drug therapy , Leishmaniasis, Visceral/mortality , Amphotericin B/adverse effects , Amphotericin B/therapeutic use , Antimony/adverse effects , Antimony/therapeutic use , Deoxycholic Acid/adverse effects , Deoxycholic Acid/therapeutic use , Drug Combinations , Humans , Phosphorylcholine/adverse effects , Phosphorylcholine/analogs & derivatives , Phosphorylcholine/therapeutic use
7.
PLoS One ; 14(6): e0218786, 2019.
Article in English | MEDLINE | ID: mdl-31242231

ABSTRACT

BACKGROUND: Liposomal amphotericin B (L-AMB) has been used for mucosal leishmaniasis (ML), but comparative studies on L-AMB and other drugs used for the treatment of ML have not been conducted. The present study aimed to evaluate the outcome of patients with ML who were treated with L-AMB. METHODS: This is a 15-year retrospective study of Brazilian patients with a confirmed diagnosis of ML. The therapeutic options for the treatment of ML consisted of L-AMB, amphotericin B lipid complex (ABLC), deoxycholate amphotericin B (d-AMB), itraconazole, antimonial pentavalent, or pentamidine. Healing, cure rate and adverse effects (AEs) associated with the drugs used to treat this condition were analyzed. RESULTS: In 71 patients, a total of 105 treatments were evaluated. The outcome of the treatment with each drug was compared, and results showed that L-AMB was superior to other therapeutic regimens (P = 0.001; odds ratio [OR] = 4.84; 95% confidence interval [CI] = 1.78-13.17). d-AMB had worse AEs than other treatment regimens (P = 0.001, OR = 0.09; 95% CI = 0.09-0.43). Approximately 66% of the patients presented with AEs during ML treatment. Although L-AMB was less nephrotoxic than d-AMB, it was associated with acute kidney injury compared with other drugs (P <0.05). CONCLUSION: L-AMB was more effective than other therapies for the treatment of ML. However, a high incidence of toxicity was associated with its use. Therapeutic choices should be reassessed, and the development of new drugs is necessary for the treatment of ML.


Subject(s)
Amphotericin B/therapeutic use , Antiprotozoal Agents/therapeutic use , Leishmania braziliensis , Leishmaniasis, Mucocutaneous/drug therapy , Acute Kidney Injury/chemically induced , Adult , Aged , Aged, 80 and over , Amphotericin B/adverse effects , Antimony/adverse effects , Antimony/therapeutic use , Antiprotozoal Agents/adverse effects , Brazil , Cohort Studies , Deoxycholic Acid/adverse effects , Deoxycholic Acid/therapeutic use , Drug Combinations , Female , Humans , Itraconazole/adverse effects , Itraconazole/therapeutic use , Liposomes , Male , Middle Aged , Pentamidine/adverse effects , Pentamidine/therapeutic use , Retrospective Studies , Treatment Outcome
8.
Ambio ; 47(8): 893-907, 2018 Dec.
Article in English | MEDLINE | ID: mdl-29549601

ABSTRACT

Iron mining activities in the Bruche valley (Vosges Mountains, France) date historically from the Roman period to the mid-nineteenth century. The geochemical and palynological study of a core from the peat bog of Le Champ du Feu allows highlighting impacts of these activities over the past millennium. Trace metal contamination is recorded for lead (Pb), arsenic, zinc, and antimony during the Middle Ages, the sixteenth century, and from cal. AD 1750-1900, with several sources distinguished by Pb isotope analyses. Forest exploitation is attested by the palynological analysis of the core, with exploitation of Fagus for smelting processes and cutting of Abies for agro-pastoralism. This approach highlights several patterns of contamination, corresponding to the mixing sources and the contamination intensity, which can be linked to the pollen assemblage zones. Hence, anthropogenic activities such as mining and farming led to long-term modification of the landscape composition in this mountainous area.


Subject(s)
Conservation of Natural Resources/history , Environmental Pollution/history , Forests , Grassland , Lead/history , Mining/history , Soil Pollutants/history , Zinc/history , Antimony/adverse effects , Antimony/analysis , Antimony/history , Arsenic/adverse effects , Arsenic/analysis , Arsenic/history , France , History, 15th Century , History, 16th Century , History, 17th Century , History, 18th Century , History, 19th Century , History, 20th Century , History, Medieval , Humans , Iron/adverse effects , Iron/history , Lead/adverse effects , Lead/analysis , Mining/trends , Models, Theoretical , Soil Pollutants/adverse effects , Spectrometry, Gamma , Zinc/adverse effects , Zinc/analysis
9.
Expert Rev Anti Infect Ther ; 16(3): 219-225, 2018 03.
Article in English | MEDLINE | ID: mdl-29411659

ABSTRACT

INTRODUCTION: Mucosal Leishmaniasis (ML) is a difficult to treat and severe form of Leishmaniasis. In general, more than 40% of subjects with ML have therapeutic failure upon the use of pentavalent antimony (Sbv) at 20mg/kg/day during 30 days. Additionally, Sbv is a toxic drug that requires parenteral administration, and many patients will need several courses to be cured. In cases that cannot be treated or cured by Sbv, the alternative is amphotericin B, another toxic and parenteral drug. As a consequence, many ML patients will be cured only after years of disease and may present several morbidities due to the aggressiveness of the disease or toxicity related to the treatment. Areas covered: We aimed to review clinical trials with Miltefosine or Sbv associated with pentoxifylline in the treatment of ML. Expert commentary: There are few studies to define more effective and safer therapy in mucosal disease caused by Leishmania, with an urgent need to supporting and funding well designed trials. Miltefosine monotherapy, as well as pentoxifylline combined with Sbv are promising therapeutic approaches to increase the cure rate of this neglected disease.


Subject(s)
Antimony/administration & dosage , Leishmaniasis, Mucocutaneous/drug therapy , Pentoxifylline/administration & dosage , Phosphorylcholine/analogs & derivatives , Animals , Antimony/adverse effects , Antiprotozoal Agents/administration & dosage , Antiprotozoal Agents/adverse effects , Drug Therapy, Combination , Humans , Leishmaniasis, Mucocutaneous/microbiology , Neglected Diseases/drug therapy , Neglected Diseases/microbiology , Pentoxifylline/adverse effects , Phosphorylcholine/administration & dosage , Phosphorylcholine/adverse effects , Treatment Outcome
10.
Europace ; 20(9): e140-e147, 2018 09 01.
Article in English | MEDLINE | ID: mdl-29016950

ABSTRACT

Aims: To evaluate whether patients with late complications of pacemakers or implantable cardioverter-defibrillators have hypersensitivity reactions to some of the materials used in generators or in electrodes, or to environmental metal burden. Methods and results: The cohort consisted of 20 men and 4 women (mean age: 62.3 ± 17.2 years) who had a history of late complications of implanted devices. The control group involved 25 men and 8 women (mean age: 64.6 ± 14.0 years) who had comparable devices, but no history of late complications. Lymphocyte transformation test was used to evaluate hypersensitivity to eight metal pollutants (antimony, manganese, mercury, molybdenum, nickel, platinum, tin, and titanium) selected by results of questionnaires on environmental burden, and by material analysis of generators and electrode surfaces. Exposures to metal pollutants were approximately the same in patients and in controls. Titanium alloy used in generators contained at least 99.32% of titanium and trace levels of other metals; higher levels of tin and platinum were detected in electrode surfaces. Hypersensitivity reactions to mercury and tin were significantly more frequent in patients than in controls (patients and controls: mercury: 68.2 and 31.1%, respectively; P = 0.022; tin: 25.0 and 3.2%, respectively; P = 0.035). In contrast, hypersensitivity to manganese was significantly more frequent in controls than in patients (patients and controls: 13.6 and 50.0%, respectively; P = 0.008). Conclusion: Our findings suggest a possible relation between hypersensitivity to metals used in implantable devices or to environmental metal burden and the occurrence of their late complications.


Subject(s)
Cardiac Resynchronization Therapy Devices/adverse effects , Defibrillators, Implantable/adverse effects , Environmental Pollutants/adverse effects , Hypersensitivity/epidemiology , Metals/adverse effects , Postoperative Complications/epidemiology , Prosthesis Implantation , Aged , Alloys , Antimony/adverse effects , Female , Humans , Hypersensitivity/etiology , Lymphocyte Activation , Male , Manganese/adverse effects , Mercury/adverse effects , Middle Aged , Molybdenum/adverse effects , Nickel/adverse effects , Pain, Postoperative/epidemiology , Platinum/adverse effects , Prosthesis-Related Infections/epidemiology , Skin Diseases/epidemiology , Tin/adverse effects , Titanium/adverse effects
11.
Int J Parasitol Drugs Drug Resist ; 7(3): 370-377, 2017 12.
Article in English | MEDLINE | ID: mdl-29035735

ABSTRACT

Widespread resistance towards antimony and reports of relapses following miltefosine treatment has severely affected the management of visceral leishmaniasis (VL) in the Indian subcontinent. Paromomycin (PMM), an aminoglycoside antibiotic, has been licensed for VL treatment in India in 2007. Although its use is still restricted in the field, unraveling the molecular mechanism of resistance towards PMM is the key to preserve the drug. In this study, PMM resistant lines were selected up to 100 µM of PMM in three distinct field isolates of Leishmania donovani at promastigote stage. The resistance induced at promastigote level was also evident in amastigotes which showed 6 fold decreases in PMM susceptibility. Comparative transcriptome profiling of PMM resistant (PMM-R) and the corresponding PMM sensitive (PMM-S) parasites revealed modulated expression of 500 genes (1.5 fold cut off) in PMM-R parasites. Selected genes were validated for their modulated expression by quantitative real-time PCR. Functional classification and pathway analysis of modulated genes indicated probable adaptations in drug resistant lines which included a) reduced oxidative phosphorylation; b) increased glycosomal succinate fermentation and substrate level phosphorylation; c) dependency on lipids and amino acids for energy generation; d) reduced DNA synthesis and increased DNA damage repair and e) decreased protein synthesis and degradation. Interestingly, PMM-R parasites showed a marked increase in PMM susceptibility in presence of verapamil and amlodipine, antagonists of Ca2+ channel that are also modulators of ABC transporters. Moreover, infection of macrophages by PMM-R parasites led to modulated nitric oxide (NO) levels while reactive oxygen species (ROS) level remained unaltered. The present study highlights the putative mechanisms of PMM resistance in Leishmania.


Subject(s)
Anti-Bacterial Agents/pharmacology , Drug Resistance/genetics , Gene Expression Profiling , Leishmania donovani/drug effects , Paromomycin/pharmacology , ATP-Binding Cassette Transporters/genetics , Amlodipine/pharmacology , Animals , Antimony/adverse effects , Antimony/pharmacology , Antiprotozoal Agents/pharmacology , Humans , Leishmaniasis, Visceral/drug therapy , Leishmaniasis, Visceral/parasitology , Life Cycle Stages/drug effects , Life Cycle Stages/genetics , Macrophages/drug effects , Macrophages/parasitology , Metabolic Networks and Pathways/drug effects , Metabolic Networks and Pathways/genetics , Mice , Nitric Oxide/metabolism , Parasitic Sensitivity Tests , Reactive Oxygen Species/metabolism , Real-Time Polymerase Chain Reaction , Verapamil/pharmacology
12.
Clin Infect Dis ; 64(1): 67-71, 2017 Jan 01.
Article in English | MEDLINE | ID: mdl-27803094

ABSTRACT

BACKGROUND: The treatment of cutaneous leishmaniasis (CL) caused by Leishmania braziliensis in Brazil with pentavalent antimony (Sbv) is associated with a high rate of failure, up to 45% of cases. In addition, Sbv can only administered parenterally and has important toxic effect. An effective, safe, and oral treatment for CL is required. METHODS: A randomized controlled clinical trial was conducted to compare the efficacy and safety of high-dosage oral fluconazole (6.5-8.0 mg/kg/d for 28 days) versus a standard Sbv protocol (20 mg/kg/d for 20 days) for the treatment of CL in Bahia, Brazil. RESULTS: A total of 53 subjects were included in the trial; 26 were treated with Sbv, and 27 with fluconazole. Intention-to-treat analysis showed initial cure rates (2 months after treatment) of 22.2% (6 of 27) in the fluconazole and 53.8% (14 of 26) in the Sbv group (P = .04). Six months after treatment, the final cure rate remained the same in both groups, without any relapses. The frequencies of adverse effects in the Sbv and fluconazole groups were similar, 34.6% versus 37% respectively. One patient treated with fluconazole discontinued treatment owing to malaise, headache, and moderate dizziness (Common Terminology Criteria for Adverse Events grade 2). CONCLUSIONS: Oral fluconazole at a dosage of 6.5-8 mg/kg/d for 28 days should not be considered an effective treatment for CL caused by L. braziliensisClinical Trials Registration. NCT01953744.


Subject(s)
Antiprotozoal Agents/therapeutic use , Fluconazole/therapeutic use , Leishmania braziliensis/drug effects , Leishmaniasis, Cutaneous/drug therapy , Leishmaniasis, Cutaneous/parasitology , Adolescent , Adult , Antimony/administration & dosage , Antimony/adverse effects , Antimony/therapeutic use , Antiprotozoal Agents/administration & dosage , Antiprotozoal Agents/adverse effects , Brazil , Female , Fluconazole/administration & dosage , Fluconazole/adverse effects , Humans , Leishmania braziliensis/genetics , Leishmaniasis, Cutaneous/diagnosis , Male , Middle Aged , Treatment Outcome , Young Adult
13.
Clin Nucl Med ; 41(4): 319-20, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26359561

ABSTRACT

A 52-year-old woman diagnosed with invasive ductal carcinoma of both breasts had a chest x-ray for preoperative assessment. A striking artifact was noted by the x-ray technologist, who, as a result, became very concerned about radiation exposure from the patient. The patient had undergone bilateral sentinel lymph node injections in the nuclear medicine department with Tc-antimony trisulfite colloid just 2 hours before the chest x-ray. Radiation exposure to the x-ray technologist was determined to be similar to 8 hours of naturally occurring background radiation (∼2.96 µSv).


Subject(s)
Antimony/adverse effects , Breast Neoplasms/diagnostic imaging , Lymph Nodes/diagnostic imaging , Radiopharmaceuticals/adverse effects , Technetium Compounds/adverse effects , Antimony/administration & dosage , Artifacts , Female , Humans , Middle Aged , Radiopharmaceuticals/administration & dosage , Technetium Compounds/administration & dosage
14.
PLoS One ; 9(8): e104055, 2014.
Article in English | MEDLINE | ID: mdl-25105501

ABSTRACT

BACKGROUND: Visceral leishmaniasis (VL) is a chronic debilitating disease endemic in tropical and subtropical areas, caused by protozoan parasites of the genus Leishmania. Annually, it is estimated the occurrence of 0.2 to 0.4 million new cases of the disease worldwide. Considering the lack of an effective vaccine the afflicted population must rely on both, an accurate diagnosis and successful treatment to combat the disease. Here we propose to evaluate the efficacy of trivalent antimonial encapsulated in conventional liposomes, in association with ascorbic acid, by monitoring its toxicity and efficacy in BALB/c mice infected with Leishmania infantum. METHODOLOGY/PRINCIPAL FINDINGS: Infected mice were subjected to single-dose treatments consisting in the administration of either free or liposome-encapsulated trivalent antimony (SbIII), in association or not with ascorbic acid. Parasite burden was assessed in the liver, spleen and bone marrow using the serial limiting dilution technique. After treatment, tissue alterations were examined by histopathology of liver, heart and kidney and confirmed by serum levels of classic biomarkers. The phenotypic profile of splenocytes was also investigated by flow cytometry. Treatment with liposome-encapsulated SbIII significantly reduced the parasite burden in the liver, spleen and bone marrow. Co-administration of ascorbic acid, with either free SbIII or its liposomal form, did not interfere with its leishmanicidal activity and promoted reduced toxicity particularly to the kidney and liver tissues. CONCLUSIONS/SIGNIFICANCE: Among the evaluated posological regimens treatment of L. infantum-infected mice with liposomal SbIII, in association with ascorbic acid, represented the best alternative as judged by its high leishmanicidal activity and absence of detectable toxic effects. Of particular importance, reduction of parasite burden in the bone marrow attested to the ability of SbIII-carrying liposomes to efficiently reach this body compartment.


Subject(s)
Antimony/adverse effects , Antimony/therapeutic use , Leishmania infantum/drug effects , Leishmaniasis, Visceral/drug therapy , Liposomes/therapeutic use , Animals , Antimony/administration & dosage , Ascorbic Acid/administration & dosage , Flow Cytometry , Immunophenotyping , Mice , Mice, Inbred BALB C , Parasite Load , Statistics, Nonparametric
15.
Mem Inst Oswaldo Cruz ; 109(4): 499-501, 2014 Jul.
Article in English | MEDLINE | ID: mdl-25004145

ABSTRACT

Antimony compounds are the cornerstone treatments for tegumentary leishmaniasis. The reactivation of herpes virus is a side effect described in few reports. We conducted an observational study to describe the incidence of herpes zoster reactivation during treatment with antimony compounds. The global incidence of herpes zoster is approximately 2.5 cases per 1,000 persons per month (or 30 cases per 1,000 persons per year). The estimated incidence of herpes zoster in patients undergoing antimony therapy is higher than previously reported.


Subject(s)
Antimony/adverse effects , Antiprotozoal Agents/adverse effects , Herpes Zoster/etiology , Herpesvirus 3, Human/physiology , Adult , Aged , Aged, 80 and over , Antimony/therapeutic use , Antiprotozoal Agents/therapeutic use , Female , Herpes Zoster/virology , Humans , Leishmaniasis, Cutaneous/drug therapy , Male , Middle Aged , Virus Activation
16.
Mem. Inst. Oswaldo Cruz ; 109(4): 499-501, 03/07/2014. tab, graf
Article in English | LILACS | ID: lil-716309

ABSTRACT

Antimony compounds are the cornerstone treatments for tegumentary leishmaniasis. The reactivation of herpes virus is a side effect described in few reports. We conducted an observational study to describe the incidence of herpes zoster reactivation during treatment with antimony compounds. The global incidence of herpes zoster is approximately 2.5 cases per 1,000 persons per month (or 30 cases per 1,000 persons per year). The estimated incidence of herpes zoster in patients undergoing antimony therapy is higher than previously reported.


Subject(s)
Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Antimony/adverse effects , Antiprotozoal Agents/adverse effects , Herpes Zoster/etiology , /physiology , Antimony/therapeutic use , Antiprotozoal Agents/therapeutic use , Herpes Zoster/virology , Leishmaniasis, Cutaneous/drug therapy , Virus Activation
19.
Rio de Janeiro; s.n; 2014. xv,85 p. tab, ilus, graf, mapas.
Thesis in Portuguese | LILACS | ID: lil-762494

ABSTRACT

O tratamento para leishmaniose cutânea (LC) utilizando antimoniais foi iniciado em 1912, no Brasil. O uso da forma pentavalente (Sb5+) se iniciou na década de 1940, e apesar de ainda ser eficaz para curar a LC efeitos adversos graves podem acontecer. Outras opções de tratamento, como pentamidina e anfotericina B também são de administração parenteral. Na tentativa de reduzir os efeitos adversos dos Sb5+, esquemas terapêuticos em doses baixas já evidenciaram ser seguros no tratamento da LC no Rio de Janeiro, sejam doses de apenas 5mg Sb5+/kg/dia por 30 dias (DB), aplicação intralesional (IL) ou em esquema de uso de uma ampola três vezes por semana (2ª/4ª/6ª) até a cura clínica...


Antimony therapy was first used to treat cutaneous leishmaniasis (CL) in 1912.Pentavalent antimonial (Sb5+) compounds were introduced as leishmaniasis therapy in the 1940s and are still efficient in curing CL, but they may cause serious adverse effects. Although there are other options for CL treatment, such as pentamidine and amphotericin B, similar to Sb5+, these drugs are also administered parenterally. To reduce the adverse effects of antimony, low-dose therapies were attempted and were proven safe in curing CL in patients in the state of Rio de Janeiro. Different schedules as 5mgSb5+/day/30 days (LowD), intralesional therapy (IL), or use of one ampoule three-times-a-week until clinical cure were proven to be efficient to cure CL...


Subject(s)
Humans , Antimony/adverse effects , Leishmaniasis, Cutaneous/diagnosis , Leishmaniasis, Cutaneous/epidemiology , Small Doses , Enzyme-Linked Immunosorbent Assay
20.
Clin Infect Dis ; 56(9): 1255-60, 2013 May.
Article in English | MEDLINE | ID: mdl-23390069

ABSTRACT

BACKGROUND: Cutaneous leishmaniasis is an ultimately self-curing disease for which systemic therapy with pentavalent antimony (Sb) is effective but with side effects. We evaluated 2 local treatments, intralesional (IL) Sb and cryotherapy, for single lesions due to Bolivian Leishmania (v.) braziliensis in a placebo-controlled study. METHODS: Patients were randomized between IL Sb (650 µg/mm(2) of lesion area on days 1, 3, and 5), cryotherapy (days 1 and 14), and placebo cream (daily for 20 days) in a 3:2:3 allocation. Lesion area was measured prior to therapy, and at 1, 3, and 6 months after therapy. The criteria for lesion cure were as follows: not doubling in size at 1 month, at least 50% diminution in size at 3 months, and complete reepithelialization at 6 months. Local adverse effects were recorded. RESULTS: Cure rates were 21 of 30 (70%; 95% confidence interval [CI], 52%-83%) for IL Sb, 4 of 20 (20%; 95% CI, 8%-42%) for cryotherapy, and 5 of 30 (17%; 95% CI, 7%-34%) for placebo cream (P < .001 for IL Sb vs each other group). IL Sb adverse events were limited to injection site pain, with a mean value of 1.0 (mild). CONCLUSIONS: The comparative cure rate, small amount of drug administered, and tolerance data for IL Sb suggest that if local therapy for single L. braziliensis lesions is chosen, this treatment is attractive. Given the difficulties of performing placebo-controlled trials in the New World, the combined placebo and cryotherapy cure rate (18%; 95% CI, 10%-31%) is likely to become the standard against which future interventions for L. braziliensis are compared. CLINICAL TRIALS REGISTRATION: NCT01300975.


Subject(s)
Antimony/administration & dosage , Antiprotozoal Agents/administration & dosage , Leishmaniasis, Cutaneous/drug therapy , Administration, Topical , Adolescent , Adult , Aged , Aged, 80 and over , Antimony/adverse effects , Antiprotozoal Agents/adverse effects , Bolivia , Child , Cryotherapy , Drug-Related Side Effects and Adverse Reactions/epidemiology , Drug-Related Side Effects and Adverse Reactions/pathology , Female , Humans , Leishmania braziliensis/drug effects , Leishmania braziliensis/isolation & purification , Leishmaniasis, Cutaneous/parasitology , Leishmaniasis, Cutaneous/pathology , Male , Middle Aged , Placebos/administration & dosage , Treatment Outcome , Young Adult
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