Intoxication aiguë et chronique au cadmium

Cadmium is a metallic impurity in various minerals. The two main cadmium exposure sources in general population are food and tobacco smoking. Its industrial exploitation has grown in the early twentieth century. Cadmium is used in accumulators or alkaline batteries (80%) and in pigments for paints or plastics (10%), in electrolytic process by deposit or by cadmium plating on metals or to reduce melting points (welding rods…). Cadmium is a cumulative toxic substance whose half-time for elimination is about 20 to 40 years and it is mainly stored in the liver and kidneys. Inhalation of cadmium oxide fumes may cause inhalation fevers or chemical pneumonitis. Cadmium chronic poisoning causes mainly renal tubulopathy and could be the cause of osteomalacia and diffuse osteoporosis. Cadmium is classified as certain carcinogen agent for humans by International Agency for Research on Cancer (IARC). The most relevant biological index exposure is the urinary cadmium. According to literature, no chelating agent can be still used in human cadmium poisonings. In France, some diseases caused by occupational exposure to cadmium may be compensated.     

Cadmium Exposure and Clinical Cardiovascular Disease: A Systematic Review

Mounting evidence supports that cadmium, a toxic metal found in tobacco, air and food, is a cardiovascular risk factor. Our objective was to conduct a systematic review of epidemiologic studies evaluating the association between cadmium exposure and cardiovascular disease. Twelve studies were identified. Overall, the pooled relative risks (95 % confidence interval) for cardiovascular disease, coronary heart disease, stroke, and peripheral arterial disease were: 1.36 (95 % CI: 1.11, 1.66), 1.30 (95 % CI: 1.12, 1.52), 1.18 (95 % CI: 0.86, 1.59), and 1.49 (95 % CI: 1.15, 1.92), respectively. The pooled relative risks for cardiovascular disease in men, women and never smokers were 1.29 (1.12, 1.48), 1.20 (0.92, 1.56) and 1.27 (0.97, 1.67), respectively. Together with experimental evidence, our review supports the association between cadmium exposure and cardiovascular disease, especially for coronary heart disease. The number of studies with stroke, heart failure (HF) and peripheral arterial disease (PAD) endpoints was small. More studies, especially studies evaluating incident endpoints, are needed.     

Lung lysyl oxidase and prolyl hydroxylase: increases induced by cadmium chloride inhalation and the effect of beta-aminopropionitrile in rats

Industrial workers who are accidentally exposed to cadmium fumes often develop severe lung damage leading to widespread peribronchiolar scarring. This study examined the effect of a single exposure of cadmium chloride aerosol on rat lung lysyl oxidase and prolyl hydroxylase, both markers of connective tissue biosynthesis. Rats were killed at 2, 4, 7, 10, and 21 days after a 2-h exposure to 0.1% Cdcl2 aerosol. Total lung lysyl oxidase was increased 14.8 times that a saline control animals by 4 days and returned to near normal values by 10 days. Interestingly, a small amount of lysyl oxidase activity was also detectable in the lung lavage of unexposed animals and was markedly elevated at the earlier times after cadmium exposure. Total lung prolyl hydroxylase activity paralleled that of lung lysyl oxidase and increased 7.4-fold by the fourth day. A significant increase in total lung hydroxyproline could be demonstrated. Administration of beta-aminopropionitrile, an irreversible inhibitor of lysyl oxidase, prevented much of the increase in lysyl oxidase activity and the accumulation of collagen. The altered tissue amounts of lysyl oxidase and prolyl hydroxylase after cadmium inhalation correlated well with the marked interstitial cell hyperplasia 4 to 5 days after exposure and suggested that connective tissue protein synthesis is activated in the interstitial cell fibroblasts soon after cadmium exposure.     

Plasmodium falciparum malaria transmission-blocking immunity under conditions of low endemicity as in Sri Lanka

Sera from acute primary Plasmodium falciparum patients in Sri Lanka were tested for the presence of antibodies against gamete antigens and for their functional effects of transmission blocking activity. Comparisons were made with corresponding data from a previous study from sera of patients from Papua New Guinea where malaria is more highly endemic. Although the prevalence of anti-gamate antibodies in the two groups were broadly similar, the prevalence of infectivity suppressive effects in the Sri Lankan sera (56%) was less than in Papua New Guinea sera (75%), suggesting that the generation of functionally effective transmission blocking antibodies requires prolonged exposure to multiple inoculations of malaria. In Papua New Guinea sera there was a good correlation between transmission blocking effects and antibody responses to Pfs 230, a known target of transmission blocking antibodies. Among the Sri Lankan sera no strong correlation was found between transmission blocking effects and the presence of antibodies to gamete surface antigens Pfs 230 nor Pfs 48/45 as detected by immunoprecipitation of radio-iodinated gamate proteins; a strong correlation was however, found between the intensity of response to gamete surface antigens by IFA and transmission blocking effects of these sera. It is possible therefore, that the antigens identified by IFA include non-protein moieties and that these may be the targets of transmission blocking antibodies in sera from acute primary infections of P. falciparum.     

A multi-center study in order to further define the molecular basis of beta-thalassemia in Thailand, Pakistan, Sri Lanka, Mauritius, Syria, and India, and to develop a simple molecular diagnostic strategy by amplification refractory mutation system-polymerase chain reaction.

The spectrum of the beta-thalassemia mutations of Thailand, Pakistan, India, Sri Lanka, Mauritius and Syria has been further characterized by a multi-center study of 1,235 transfusion-dependent patients, and the mutations discovered used to assess the fidelity of a simple diagnostic strategy. A total of 44 beta-thalassemia mutations were identified either by allele-specific oligonucleotide hybridization, amplification with allele-specific primers, or DNA sequencing of amplified product. The results confirm and extend earlier findings for Thailand, Pakistan, India, Mauritius and Syria. This is the first detailed report of the spectrum of mutations for Sri Lanka. Two novel mutations were identified, codon 55 (-A) and IVS-I-129 (A-->C), both found in Sri Lankan patients. Two beta-thalassemia mutations were found to coexist in one beta-globin gene: Sri Lankan patients homozygous for the beta0 codon 16 (-C) frameshift were also homozygous for the beta+ codon 10 (C-->A) mutation. Studies of Sri Lankan, Pakistani, and Indian carriers suggest the codon 10 (C-->A) mutation is just a rare polymorphism on an ancestral allele, on which the beta0 codon 16 (-C) mutation has arisen. Each country was found to have only a few common mutations accounting for 70% or more of the beta-thalassemia alleles. A panel of primers to diagnose the majority of the mutations by the amplification refractory mutation system was developed, enabling a simple molecular diagnostic strategy to be introduced for each country participating in the multi-center study.     

The regional sero-epidemiology of rhinosporidiosis in Sri Lankan humans and animals

No data is available in the world literature on serum anti-rhinosporidial antibody levels in animals, and as far as we aware this is the first report. Although rhinosporidiosis in farm and domestic animals has been widely reported from other countries, rhinosporidiosis in animals has not been reported in Sri Lanka, though this country has the highest world-wide prevalence of human rhinosporidiosis on a unit-population basis. Serum IgG titres in 6 species of Sri Lankan animals (buffalo, cat, cattle, dog, goat, horse; total 291) were assayed by the Immuno blot (dot-ELISA) method on nitrocellulose paper and were compared with serum IgG titres in normal Sri Lankan human subjects (total 211) in different geographical areas, and in human Sri Lankan patients with rhinosporidiosis as reference values (total 36). Sensitization to rhinosporidial antigen(s) was detected in all 6 species of animals and the highest titres (1/3200) were found in cats, and free-grazing horses. Cattle showed higher levels of antibody than buffaloes. The titres in these animals are compared with world reports on overt rhinosporidiosis in these species, and with titres in normal Sri Lankan humans. Human, but not animal titres showed variations compatible with the regional prevalence of rhinosporidiosis. The variations in titres in animals especially horses, were probably more related to their mode of feeding, while in humans the titres in normal persons were probably related to the rhinosporidial-endemicity of their respective regions. No conclusions from sero-positivity in animals could be made regarding the absence of reports on rhinosporidiosis as an overt disease in these Sri Lankan animal species but the possibility of a genetically-determined insusceptibility to rhinosporidiosis in Sri Lanka, is considered. Rhinosporidium seeberi-specific PCR positive reactions were obtained with nasal scrapings from cattle that microscopically showed PAS+ bodies that were compatible with rhinosporidial sporangia. Sequence-analysis of the reactions products from five positive R. seeberi-specific PCR samples (four in this study and 1 in a previous study) gave results confirmatory of R. seeberi.     

A MULTI-CENTER STUDY IN ORDER TO FURTHER DEFINE THE MOLECULAR BASIS OF β-THALASSEMIA IN THAILAND,PAKISTAN, SRI LANKA,MAURITIUS, SYRIA,AND INDIA,AND TO DEVELOP A SIMPLE MOLECULAR DIAGNOSTIC STRATEGY BY AMPLIFICATION REFRACTORY MUTATION SYSTEM-POLYMERASE CHAIN REACTION

The spectrum of the β-thalassemia mutations of Thailand, Pakistan, India, Sri Lanka, Mauritius and Syria has been further characterized by a multi-center study of 1,235 transfusion-dependent patients, and the mutations discovered used to assess the fidelity of a simple diagnostic strategy. A total of 44 β-thalassemia mutations were identified either by allele-specific oligonucleotide hybridization, amplification with allele-specific primers, or DNA sequencing of amplified product. The results confirm and extend earlier findings for Thailand, Pakistan, India, Mauritius and Syria. This is the first detailed report of the spectrum of mutations for Sri Lanka. Two novel mutations were identified, codon 55 (?A) and IVS-I-129 (A → C), both found in Sri Lankan patients. Two β-thalassemia mutations were found to coexist in one β-globin gene: Sri Lankan patients homozygous for the β⁰ codon 16 (?C) frameshift were also homozygous for the β⁺ codon 10 (C → A) mutation. Studies of Sri Lankan, Pakistani, and Indian carriers suggest the codon 10 (C → A) mutation is just a rare polymorphism on an ancestral allele, on which the β⁰ codon 16 (?C) mutation has arisen. Each country was found to have only a few common mutations accounting for 70% or more of the β-thalassemia alleles. A panel of primers to diagnose the majority of the mutations by the amplification refractory mutation system was developed, enabling a simple molecular diagnostic strategy to be introduced for each country participating in the multi-center study.     

Biochemical and physiologic changes in lungs of rats exposed to a cadmium chloride aerosol.

The purpose of this study was to examine the in vivo effects of acute exposure to a cadmium chloride aerosol on the activity of pulmonary enzymes and selected physiologic parameters that are altered by exposure to oxidant agents. Male rats were exposed for 1 hour to 0.5 per cent aerosol of cadmium chloride. At 1,5, and 11 days after exposure to cadmium chloride, exposed rats compared to control rats (data expressed as per cent of control values) had lung-to-body weight ratios of 192, 174, and 140 per cent; lung glucose-6-phosphate dehydrogenase activities of 90, 107, and 135 per cent; lung superoxide dismutase activities of 96, 101, and 132 per cent; tidal volumes of 62, 63, and 89 per cent; respiratory frequencies of 170, 145, and 108 per cent; and lung weight-specific static deflation volumes at 30 cm water of 30, 13, and 31 per cent. A zero-order clearance of cadmium from whole lung was observed, with a half-time of 27.4 days. Light microscopic examination of lung tissue revealed initial pulmonary edema on day 1 that progressed to interstitial pneumonitis on day 5, with some recovery by 11 days after exposure. The cadmium induced biochemical, physiologic, and pathologic alterations were similar to the responses observed in lungs of rats exposed to a wide variety of pulmonary irritants; thus, the changes observed may represent a nonspecific response to tissue injury.     

Sri Lankan National Melioidosis Surveillance Program Uncovers a Nationwide Distribution of Invasive Melioidosis

The epidemiologic status of melioidosis in Sri Lanka was unclear from the few previous case reports. We established laboratory support for a case definition and started a nationwide case-finding study. Suspected Burkholderia pseudomallei isolates were collated, identified by polymerase chain reaction assay, referred for Matrix Assisted Laser Desorption Ionization-Time of Flight analysis and multilocus sequence typing (MLST), and named according to the international MLST database. Between 2006 and early 2014, there were 32 patients with culture-confirmed melioidosis with an increasing annual total and a falling fatality rate. Patients were predominantly from rural communities, diabetic, and male. The major clinical presentations were sepsis, pneumonia, soft tissue and joint infections, and other focal infection. Burkholderia pseudomallei isolates came from all parts of Sri Lanka except the Sabaragamuwa Province, the south central hill country, and parts of northern Sri Lanka. Bacterial isolates belonged to 18 multilocus sequence types, one of which (ST 1137) was associated with septicemia and a single-organ focus (Fisher''s exact, P = 0.004). Melioidosis is an established endemic infection throughout Sri Lanka, and is caused by multiple genotypes of B. pseudomallei, which form a distinct geographic group based upon related sequence types (BURST) cluster at the junction of the southeast Asian and Australasian clades.     

The effects on bone of environmental cadmium exposure--summary of recent epidemiological studies

In Itai-itai disease, which is the most severe manifestation of environmental cadmium exposure, the bone features are characteristic of osteomalacia induced by renal tubular dysfunction and osteoporosis. Lower bone mass and higher bone turnover have been observed in inhabitants of cadmium-exposed areas, compared with people in nonexposed areas in Japan. Decreased bone mass and increased bone fracture have been reported recently in large-scale epidemiological studies, conducted in Belgium and Sweden. An association between higher urinary cadmium and lower bone mass was also found in female Japanese. These studies suggest that environmental cadmium exposure could be a risk factor of osteoporosis even in the general population in Japan. The effect on bone could be caused indirectly through renal damage induced by cadmium exposure, or directly via an effect of cadmium on bone itself.     

Cellular proliferation induced in the lung by cadmium aerosol.

Rats were exposed to a polydispersed aerosol of 0.1 per cent cadmium chloride in physiologic saline for a single period of 2 hours, and the evolution of damage was followed for a 10-day period. Control animals were unexposed rats and rats exposed to an aerosol of physiologic saline. Wet lung weight doubled by the fourth day in animals exposed to cadmium chloride, but not in the control groups. Apart from a transient increase in fluid content at 1 day, there was no evidence that the lung weight gain was due to inflammatory edema. Uptake of [3H]thymidine markedly increased during the first four days after exposure to cadmium chloride. Light autoradiography showed that [3H]thymidine labeling occurred almost exclusively in Type II alveolar cells at 1 day: later, the label appeared in interstitial cells and cells lying free within alveoli. These changes correlated well (r=0.70) with the increase in deoxyribonucleic acid on the fourth day after exposure. Uptake of [3H]thymidine and deoxyribonucleic acid content in rats exposed to cadmium chloride showed a significant difference from the control groups (P less than 0.001). These experiments demonstrate that exposure to cadmium chloride aerosol evokes a wave of cellular proliferation in rat lung. This finding is of interest, because heavy industrial exposure to cadmium in humans is known to be associated with severe physiologic impairment and anatomic damage.     

The first intermediate host of Paragonimus westermani in Sri Lanka

Freshwater snails (family Paludomidae, genus Paludomus) were collected from streams in Hedeniya and Peradeniya (the campus of Peradeniya University), Kandy district, Central Province, Sri Lanka, and found to harbor rediae and cercariae of a Paragonimus sp. These larvae were identified as Paragonimus westermani by using ITS2 DNA sequences. The infection rates of P. westermani in Paludomus sp. in Hedeniya and Peradeniya were 0.1% (one of 1014) and 0.2% (two of 1006), respectively. The snail has not been identified to species in the present study. This is the first report of the snail host of Paragonimus in Sri Lanka.     

Nano Selenium—Enriched Probiotics as Functional Food Products against Cadmium Liver Toxicity

Since cadmium is a toxic metal that can cause serious health problems for humans, it is necessary to find bioremediation solutions to reduce its harmful effects. The main goal of our work was to develop a functional food based on elemental selenium nanoparticles (SeNPs) obtained by green synthesis using Lactobacillus casei and to validate their ability to annihilate the hepatic toxic effects induced by cadmium. The characterization of SeNPs was assessed by UV–Vis spectroscopy, FTIR, XRD, DLS and TEM. In order to investigate the dose-dependent protective effects of SeNPs on Cd liver toxicity, mice were assigned to eight experimental groups and fed by gavage, with 5 mg/kg b.w. cadmium, respectively, with co-administration with SeNPs or lacto-SeNPs (LSeNPs) in 3 doses (0.1, 0.2 and 0.4 mg/kg b.w.) for 30 days. The protective effect was demonstrated by the restoration of blood hepatic markers (AST, ALT, GGT and total bilirubin) and antioxidant enzymes, such as catalase (CAT) and glutathione peroxidase (GPx). Moreover, the antioxidant capacity of mice plasma by the FRAP assay, revealed the highest antioxidant capacity for the 0.2 mg/kg LSeNPs group. Histopathological analysis demonstrated the morphological alteration in the group that received only cadmium and was restored after the administration of SeNPs or LSeNPs, while the immunohistochemical analysis of the bcl family revealed anti-apoptotic effects; the Q-PCR analysis showed an upregulation of hepatic inflammatory markers for the group exposed to Cd and a decreased value for the groups receiving oral SeNPs/ LSeNPs in a dose-dependent manner. The best protective effects were obtained for LSeNPs. A functional food that includes both probiotic bacteria and elemental SeNPs could be successfully used to annihilate Cd-induced liver toxicity, and to improve both nutritional values and health benefits.     

High seasonal malaria transmission rates in the intermediate rainfall zone of Sri Lanka.

Malaria transmission was studied at Nikawehera, a long-established farming village, located in the intermediate rainfall zone of Sri Lanka. Observations were made over a 12-month period (October-September) that included the main rainy season which occurred during the north-east monsoon in November-January. Anolpheles culicifacies, the recognized vector of malaria in Sri Lanka, was the predominant anopheline mosquito collected by human night baiting at Nikawehera. High entomological inoculation rates with An. culcifacies (0.12/hour for Plasmodium vivax) were observed during the height of the transmission season which occurs during, and immediately after, the north-east monsoon. Anolpheles subpictus was identified as a possible additional vector at Nikawehera. Anopheles annularis, a major vector at Weheragala, a site in a new irrigation development (the Mahaweli Scheme) located 70 km away in the dry zone, was not collected by human baiting at Nikawehera. Clinical, entomological and parasitological data suggest that malaria is hyperendemic at Nikawehera, with high seasonal transmission rates.     

Increased platelet activation in subjects chronically exposed to cadmium: A pilot study

Cadmium exposure has been reported to be associated with the risk of vascular disorders. Here, we investigated platelet activity in subjects with chronic cadmium exposure. Eighteen and 15 women participated in this study as chronically cadmium-exposed and control non-exposed subjects, respectively. Plasma P-selectin and CD40 ligand (CD40L), soluble markers of platelet activation, were measured. Platelet aggregation in whole blood, P-selectin and activated glycoprotein (aGP) IIb/IIIa expression on platelets and platelet–leukocyte aggregates were determined. The levels of plasma P-selectin and CD40L increased in subjects with chronic cadmium exposure compared with control subjects. Platelet aggregation induced by adenosine diphosphate (ADP) was higher in cadmium-exposed subjects than control subjects. Cadmium-exposed subjects had higher baseline and ADP-induced aGPIIb/IIIa expression on platelets than control subjects. Platelet–neutrophil aggregates also increased in cadmium-exposed subjects. Blood cadmium correlated with ADP-induced aggregation, aGPIIb/IIIa expression and platelet–neutrophil aggregates, while urinary cadmium correlated with soluble P-selectin. However, cadmium only at high concentration (15?µM) could potentiate ADP-induced platelet activation in vitro. In conclusion, our pilot data show that cadmium-exposed subjects have increased baseline platelet activation and reactivity.     

Temporal trend of cadmium exposure in the United States population suggests gender specificities

Background: Over the years, environmental cadmium exposure has been linked to increased mortality. Over the years, the use of cadmium has generally decreased. Aims: Although even relatively low levels of cadmium have been associated with increased mortality in the general population, whether this applies to blood cadmium is not well understood. Methods: The authors analysed data of the National Health and Nutrition Examination Survey to study the temporal trend of cadmium exposure in the period 1988–2006 and the risk of all‐cause, cancer and cardiovascular mortality associated with blood cadmium levels. Results: Urinary cadmium decreased significantly over time in males (0.58 (0.01) mcg/g to 0.41 (0.01) mcg/g; P < 0.001) but not in females (0.71 (0.09) mcg/g to 0.63 (0.08) mcg/g; P= 0.66). All‐cause mortality was significantly higher in the highest quartiles compared with the lowest quartile of blood cadmium in both males (hazard ratio 1.89, 95% confidence interval 1.22, 2.89; P= 0.005) and females (hazard ratio 2.03, 95% confidence interval 1.06, 3.89; P= 0.035) after adjustment for age, race/ethnicity, smoke status, alcohol intake, annual household income and body mass index. There was also a significant association with cardiovascular mortality in females (P= 0.025). Conclusions: Our data show that elevated blood cadmium levels are associated with elevated mortality, that there seem to be gender differences in temporal trends of cadmium exposure and that blood cadmium is a proxy of chronic cadmium exposure.     

Manifestations and outcomes of leptospirosis during local outbreaks in high endemic districts of Sri Lanka: A retrospective multi-center study

Objective: To determine the clinical presentations and disease outcomes of suspected and confirmed cases of leptospirosis from 3 high endemic districts of Sri Lanka, during outbreaks reported between 2013 and 2017. Methods: The retrospective multi-center study was carried out during 2013-2017 in 5 selected hospitals representing 3 high endemic districts in Sri Lanka. Clinically suspected leptospirosis patients were recruited according to the Communicable Disease Epidemiology Profile Sri Lanka, WHO. Leptospirosis was confirmed by either single microscopic agglutination test titre 1: 400 or by positive polymerase chain reaction(PCR) test result. Results: Out of 372 clinically suspected cases, 29.00% were confirmed as leptospirosis cases by either microscopic agglutination test(50.00%) or positive polymerase chain reaction(52.77%) and 12.90% were presumptively identified as leptospirosis. Clinical symptoms(headache, vomiting, jaundice and dyspnoea) and variations in haematological parameters(haemoglobin, platelet count) and biochemical parameters(serum creatinine, serum urea, serum bilirubin and C-reactive protein) were associated with confirmed leptospirosis(P0.05). Acute kidney injury, meningitis, myocarditis, pulmonary haemorrhage and acute liver failure was seen among 21.30%, 12.04%, 6.48%, 6.48%, 5.56%, respectively with 4.63% fatality among the leptospirosis confirmed patients. The sensitivity, specificity, positive predictive value and negative predictive value of the case definition of Ministry of Health, Sri Lanka were 96.29%, 9.09%, 31.13%and 85.71%, respectively, when benchmarked against either positive polymerase chain reaction or microscopic agglutination test as the gold standard. Conclusions: Acute kidney injury is the predominant complication observed among the leptospirosis confirmed patients. However, pulmonary haemorrhage is predominantly associated with mortality. The case definition of Ministry of Health, Sri Lanka is found to have higher sensitivity and enabled the screening of all probable cases of leptospirosis.     

Geographic Structure of Plasmodium vivax: Microsatellite Analysis of Parasite Populations from Sri Lanka, Myanmar, and Ethiopia

Genetic diversity and population structure of Plasmodium vivax parasites can predict the origin and spread of novel variants within a population enabling population specific malaria control measures. We analyzed the genetic diversity and population structure of 425 P. vivax isolates from Sri Lanka, Myanmar, and Ethiopia using 12 trinucleotide and tetranucleotide microsatellite markers. All three parasite populations were highly polymorphic with 3–44 alleles per locus. Approximately 65% were multiple-clone infections. Mean genetic diversity (H_E) was 0.7517 in Ethiopia, 0.8450 in Myanmar, and 0.8610 in Sri Lanka. Significant linkage disequilibrium was maintained. Population structure showed two clusters (Asian and African) according to geography and ancestry. Strong clustering of outbreak isolates from Sri Lanka and Ethiopia was observed. Predictive power of ancestry using two-thirds of the isolates as a model identified 78.2% of isolates accurately as being African or Asian. Microsatellite analysis is a useful tool for mapping short-term outbreaks of malaria and for predicting ancestry.