Antimony
Antimony Potassium Tartrate
Antimony Sodium Gluconate
Meglumine
Leishmania donovani
Leishmaniasis, Visceral
Organometallic Compounds
Leishmaniasis, Cutaneous
Technetium Compounds
Arsenic
Tartrates
Leishmaniasis
Leishmania
Leishmania braziliensis
Neutron Activation Analysis
Leishmaniasis, Mucocutaneous
Drug Resistance
Ion Pumps
Overexpression of the multidrug resistance-associated protein (MRP1) in human heavy metal-selected tumor cells. (1/319)
Cellular and molecular mechanisms involved in the resistance to cytotoxic heavy metals remain largely to be characterized in mammalian cells. To this end, we have analyzed a metal-resistant variant of the human lung cancer GLC4 cell line that we have selected by a step-wise procedure in potassium antimony tartrate. Antimony-selected cells, termed GLC4/Sb30 cells, poorly accumulated antimony through an enhanced cellular efflux of metal, thus suggesting up-regulation of a membrane export system in these cells. Indeed, GLC4/Sb30 cells were found to display a functional overexpression of the multidrug resistance-associated protein MRP1, a drug export pump, as demonstrated by Western blotting, reverse transcriptase-polymerase chain reaction and calcein accumulation assays. Moreover, MK571, a potent inhibitor of MRP1 activity, was found to markedly down-modulate resistance of GLC4/Sb30 cells to antimony and to decrease cellular export of the metal. Taken together, our data support the conclusion that overexpression of functional MRP1 likely represents one major mechanism by which human cells can escape the cytotoxic effects of heavy metals. (+info)Chemistry and toxicity of flame retardants for plastics. (2/319)
An overview of commercially used flame retardants is give. The most used flame retardants are illustrated and the seven major markets, which use 96% of all flame-retarded polymers, are described. Annual flame retardant growth rate for each major market is also projected. Toxicity data are reviewed on only those compositions that are considered commercially significant today. This includes 18 compounds or families of compounds and four inherently flame-retarded polymers. Toxicological studies of flame retardants for most synthetic materials are of recent origin and only a few of the compounds have been evaluated in any great detail. Considerable toxicological problems may exist in the manufacturing of some flame retardants, their by-products, and possible decomposition products. (+info)Asp45 is a Mg2+ ligand in the ArsA ATPase. (3/319)
The ATPase activity of ArsA, the catalytic subunit of the plasmid-encoded, ATP-dependent extrusion pump for arsenicals and antimonials in Escherichia coli, is allosterically activated by arsenite or antimonite. Magnesium is essential for ATPase activity. To examine the role of Asp45, mutants were constructed in which Asp45 was changed to Glu, Asn, or Ala. Cells expressing these mutated arsA genes lost arsenite resistance to varying degrees. Purified D45A and D45N enzymes were inactive. The purified D45E enzyme exhibited approximately 5% of the wild type activity with about a 5-fold decrease in affinity for Mg2+. Intrinsic tryptophan fluorescence was used to probe Mg2+ binding. ArsA containing only Trp159 exhibited fluorescence enhancement upon the addition of MgATP, which was absent in D45N and D45A. As another measure of conformation, limited trypsin digestion was used to estimate the surface accessibility of residues in ArsA. ATP and Sb(III) synergistically protected wild type ArsA from trypsin digestion. Subsequent addition of Mg2+ increased trypsin sensitivity. D45N and D45A remained protected by ATP and Sb(III) but lost the Mg2+ effect. D45E exhibited an intermediate Mg2+ response. These results indicate that Asp45 is a Mg2+-responsive residue, consistent with its function as a Mg2+ ligand. (+info)Short report: improved diagnosis and follow-up of canine leishmaniasis using amastigote-based indirect immunofluorescence. (4/319)
A comparison of an indirect immunofluorescence test using promastigotes (IFATp) or cultured amastigotes (IFATa) in the diagnosis and follow-up of canine leishmaniasis caused by Leishmania infantum was carried out. Results obtained with both diagnostic methods were in good agreement although the IFATa titration was more sensitive than the currently used IFATp without losing specificity. The higher sensitivity of the amastigote-based IFAT resulted in an earlier diagnosis in the absence of clinical signs. Both methods showed comparable results for monitoring the clinical evolution of naturally infected and treated (meglumine antimoniate plus allopurinol) dogs. (+info)High frequency of serious side effects from meglumine antimoniate given without an upper limit dose for the treatment of visceral leishmaniasis in human immunodeficiency virus type-1-infected patients. (5/319)
Organic pentavalent antimonials are one of the mainstays of treatment for visceral leishmaniasis (VL). Few data are available on the toxicity and efficacy of these drugs at the dosing schedule recommended by the Centers for Disease Control and Prevention (CDC) (Atlanta, GA). We analyzed 25 VL episodes in human immunodeficiency virus (HIV)-infected patients who were treated with meglumine antimoniate (MA) at the CDC-recommended dose in southern Spain. Adverse effects were observed in 14 (56%) VL episodes. In 7 (28%), treatment with MA was permanently discontinued due to serious adverse effects that included acute pancreatitis, acute renal failure, and leukopenia. Three (12%) patients died during therapy due to severe acute pancreatitis attributable to MA. The dosing regimen of MA currently recommended for treating VL is associated with a high rate of serious side effects in HIV-1-infected patients. (+info)Roles of endogenous gamma interferon and macrophage microbicidal mechanisms in host response to chemotherapy in experimental visceral leishmaniasis. (6/319)
In experimental visceral leishmaniasis, in which the tissue macrophage is the target, in vivo responsiveness to conventional chemotherapy (pentavalent antimony [Sb]) requires a T-cell-dependent mechanism. To determine if this mechanism involves gamma interferon (IFN-gamma)-induced activation and/or specific IFN-gamma-regulated macrophage leishmanicidal mechanisms (generation of reactive nitrogen or oxygen intermediates, we treated gene-deficient mice infected with Leishmania donovani. In IFN-gamma gene knockout (GKO) mice, Sb inhibited but did not kill intracellular L. donovani (2% killing versus 76% in controls). Sb was active (>94% killing), however, in both inducible nitric oxide synthase (iNOS) knockout (KO) and respiratory burst (phagocyte oxidase)-deficient chronic granulomatous disease (X-CGD) mice. Sb's efficacy was also maintained in doubly deficient animals (X-CGD mice treated with an iNOS inhibitor). In contrast to Sb, amphotericin B (AmB) induced high-level killing in GKO mice; AmB was also fully active in iNOS KO and X-CGD animals. Although resolution of L. donovani infection requires iNOS, residual visceral infection remained largely suppressed in iNOS KO mice treated with Sb or AmB. These results indicate that endogenous IFN-gamma regulates the leishmanicidal response to Sb and achieves this effect via a pathway unrelated to the macrophage's primary microbicidal mechanisms. The role of IFN-gamma is selective, since it is not a cofactor in the response to AmB. Treatment with either Sb or AmB permits an iNOS-independent mechanism to emerge and control residual intracellular L. donovani infection. (+info)Ultrastructural histochemical alteration of the plasma membrane in chronic myelocytic leukemia. (7/319)
Ultrastructural histochemical evaluation of the surface of normal human blood and bone marrow cells exposed to the pyroantimonate-osmium (PAO) reaction indicated the selective binding of pyroantimonate to certain cations (calcium, magnesium, and possibly sodium) associated with the plasma membrane of neutrophilic leukocytes and their developmental forms. Other leukocytes and their precursors did not exhibit plasma membrane PAO reactivity. The extent of surface binding was related to cell maturity, with maximal labeling evident in the mid and late promyelocytes; decreased binding occurred with subsequent maturation while myeloblasts were nonreactive. This study was initiated to ascertain if histochemical surface modifications of neutrophilic cells occur in certain myeloproliferative disorders. In this regard, we have been able to demonstrate a distinctive defect in the plasma membrane PAO binding characteristics of the leukemic cells in chronic myelocytic leukemia (CML). Limited binding of pyroantimonate to the plasma membrane of the leukemic cell series in four patients with CML contrasted with that of the normal granulocytic cell series and the neutrophilic cells seen in myelomonocytic leukemia (two patients), myelofibrosis (one patient), and acute myelocytic leukemia (three patients). Comparison of surface PAO reactivity of neutrophilic cells in all stages of maturation in two patients with CML in blast crisis revealed that, in the patient with 30% circulating blast cells, PAO reactivity was identical to that noted in CML, while in the patient with 80% circulating blast forms, the PAO reactivity of the maturing neutrophilic cells more nearly resembled that observed in neutrophilic cells from normal individuals. Many neutrophilic cells from patients with myelofibrosis and myelomonocytic leukemia and from one patient in severe blast crisis had large surface deposits of pyroantimonate considered to reflect increased membrane-associated reactive cation. (+info)Concentrations of antimony in infants dying from SIDS and infants dying from other causes. (8/319)
OBJECTIVES: Raised concentrations of antimony have been found in infants dying of sudden infant death syndrome (SIDS). The presumed source of this antimony is toxic gases generated from fire retardants that are present in cot mattresses. The aim of this study was to determine the role of antimony in SIDS. DESIGN: Samples of liver, brain, serum, and urine were collected from all patients dying from SIDS and a group of aged matched control infants who had died of other causes. SETTING: Nationwide study in Ireland. SUBJECTS: 52 infants dying from SIDS and 19 control infants aged > 7 days and < 1 year. RESULTS: The median concentration of antimony in the liver and brain of infants dying of SIDS was < 1 ng/g, with no difference detected between the infants dying from SIDS and the control infants. The range of antimony in the serum of infants dying of SIDS was 0.09-0.71 microg/litre (median, 0.26). Although no difference was found between infants dying from SIDS and control infants, SIDS infants were found to have higher concentrations when compared with healthy infants in the 1st year of life, probably as a result of release of antimony into serum after death. Urine antimony concentrations in infants dying from SIDS were < 3.91 ng/mg (corrected for creatinine) and similar to values found both in control infants and healthy infants. CONCLUSION: There is no evidence to support a causal role for antimony in SIDS. (+info)Antimony is a toxic metallic element with the symbol Sb and atomic number 51. It exists in several allotropic forms and can be found naturally as the mineral stibnite. Antimony has been used for centuries in various applications, including medicinal ones, although its use in medicine has largely fallen out of favor due to its toxicity.
In a medical context, antimony may still be encountered in certain medications used to treat parasitic infections, such as pentavalent antimony compounds (e.g., sodium stibogluconate and meglumine antimoniate) for the treatment of leishmaniasis. However, these drugs can have significant side effects and their use is typically reserved for severe cases that cannot be treated with other medications.
It's important to note that exposure to antimony in high concentrations or over prolonged periods can lead to serious health issues, including respiratory problems, skin irritation, gastrointestinal symptoms, and even neurological damage. Therefore, handling antimony-containing substances should be done with caution and appropriate safety measures.
Antimony potassium tartrate is an inorganic compound with the chemical formula KSbC4H4O7. It is a white crystalline solid that is soluble in water and has been used historically in medical treatments, most notably in the treatment of leishmaniasis, a parasitic disease. However, due to its potential toxicity and the availability of safer alternatives, it is no longer commonly used in modern medicine.
Antimony sodium gluconate is a chemical compound that contains antimony, sodium, and gluconic acid. It is used primarily as a medication to treat the parasitic infection known as leishmaniasis, which is caused by a protozoan parasite and is transmitted through the bite of certain sandflies.
The compound works by inhibiting the growth of the parasite within the host's body. Antimony sodium gluconate is administered intravenously or intramuscularly, depending on the severity of the infection and the patient's overall health status.
It is important to note that antimony sodium gluconate can have significant side effects, including nausea, vomiting, diarrhea, abdominal pain, and muscle weakness. In some cases, it may also cause more serious complications such as cardiac arrhythmias or kidney damage. Therefore, it should only be administered under the close supervision of a healthcare professional.
Antiprotozoal agents are a type of medication used to treat protozoal infections, which are infections caused by microscopic single-celled organisms called protozoa. These agents work by either killing the protozoa or inhibiting their growth and reproduction. They can be administered through various routes, including oral, topical, and intravenous, depending on the type of infection and the severity of the illness.
Examples of antiprotozoal agents include:
* Metronidazole, tinidazole, and nitazoxanide for treating infections caused by Giardia lamblia and Entamoeba histolytica.
* Atovaquone, clindamycin, and pyrimethamine-sulfadoxine for treating malaria caused by Plasmodium falciparum or other Plasmodium species.
* Pentamidine and suramin for treating African trypanosomiasis (sleeping sickness) caused by Trypanosoma brucei gambiense or T. b. rhodesiense.
* Nitroimidazoles, such as benznidazole and nifurtimox, for treating Chagas disease caused by Trypanosoma cruzi.
* Sodium stibogluconate and paromomycin for treating leishmaniasis caused by Leishmania species.
Antiprotozoal agents can have side effects, ranging from mild to severe, depending on the drug and the individual patient's response. It is essential to follow the prescribing physician's instructions carefully when taking these medications and report any adverse reactions promptly.
Meglumine is not a medical condition but a medication. It is an anticholinergic drug that is used as a diagnostic aid in the form of meglumine iodide, which is used to test for kidney function and to visualize the urinary tract. Meglumine is an amino sugar that is used as a counterion to combine with iodine to make meglumine iodide. It works by increasing the excretion of iodine through the kidneys, which helps to enhance the visibility of the urinary tract during imaging studies.
'Leishmania donovani' is a species of protozoan parasite that causes a severe form of visceral leishmaniasis, also known as kala-azar. This disease primarily affects the spleen, liver, and bone marrow, leading to symptoms such as fever, weight loss, anemia, and enlargement of the spleen and liver. The parasite is transmitted to humans through the bite of infected female sandflies. It's worth noting that this organism can also affect dogs and other animals, causing a disease known as canine leishmaniasis.
Visceral leishmaniasis (VL), also known as kala-azar, is a systemic protozoan disease caused by the Leishmania donovani complex. It is the most severe form of leishmaniasis and is characterized by fever, weight loss, anemia, hepatosplenomegaly, and pancytopenia. If left untreated, it can be fatal in over 95% of cases within 2 years of onset of symptoms. It is transmitted to humans through the bite of infected female sandflies (Phlebotomus spp. or Lutzomyia spp.). The parasites enter the skin and are taken up by macrophages, where they transform into amastigotes and spread to internal organs such as the spleen, liver, and bone marrow. Diagnosis is typically made through demonstration of the parasite in tissue samples or through serological tests. Treatment options include antimonial drugs, amphotericin B, miltefosine, and paromomycin. Prevention measures include vector control, early detection and treatment, and protection against sandfly bites.
Organometallic compounds are a type of chemical compound that contain at least one metal-carbon bond. This means that the metal is directly attached to carbon atom(s) from an organic molecule. These compounds can be synthesized through various methods, and they have found widespread use in industrial and medicinal applications, including catalysis, polymerization, and pharmaceuticals.
It's worth noting that while organometallic compounds contain metal-carbon bonds, not all compounds with metal-carbon bonds are considered organometallic. For example, in classical inorganic chemistry, simple salts of metal carbonyls (M(CO)n) are not typically classified as organometallic, but rather as metal carbonyl complexes. The distinction between these classes of compounds can sometimes be subtle and is a matter of ongoing debate among chemists.
Cutaneous leishmaniasis is a neglected tropical disease caused by infection with Leishmania parasites, which are transmitted through the bite of infected female sandflies. The disease primarily affects the skin and mucous membranes, causing lesions that can be disfiguring and stigmatizing. There are several clinical forms of cutaneous leishmaniasis, including localized, disseminated, and mucocutaneous.
Localized cutaneous leishmaniasis is the most common form of the disease, characterized by the development of one or more nodular or ulcerative lesions at the site of the sandfly bite, typically appearing within a few weeks to several months after exposure. The lesions may vary in size and appearance, ranging from small papules to large plaques or ulcers, and can be painful or pruritic (itchy).
Disseminated cutaneous leishmaniasis is a more severe form of the disease, characterized by the widespread dissemination of lesions across the body. This form of the disease typically affects people with weakened immune systems, such as those with HIV/AIDS or those receiving immunosuppressive therapy.
Mucocutaneous leishmaniasis is a rare but severe form of the disease, characterized by the spread of infection from the skin to the mucous membranes of the nose, mouth, and throat. This can result in extensive tissue destruction, disfigurement, and functional impairment.
Cutaneous leishmaniasis is diagnosed through a combination of clinical evaluation, epidemiological data, and laboratory tests such as parasite detection using microscopy or molecular techniques, or serological tests to detect antibodies against the Leishmania parasites. Treatment options for cutaneous leishmaniasis include systemic or topical medications, such as antimonial drugs, miltefosine, or pentamidine, as well as physical treatments such as cryotherapy or thermotherapy. The choice of treatment depends on various factors, including the species of Leishmania involved, the clinical form of the disease, and the patient's overall health status.
Technetium compounds refer to chemical substances that contain the radioactive technetium (Tc) element. Technetium is a naturally rare element and does not have any stable isotopes, making it only exist in trace amounts in the Earth's crust. However, it can be produced artificially in nuclear reactors.
Technetium compounds are widely used in medical imaging as radioactive tracers in diagnostic procedures. The most common technetium compound is Technetium-99m (Tc-99m), which has a half-life of 6 hours and emits gamma rays that can be detected by external cameras. Tc-99m is often bound to various pharmaceuticals, such as methylene diphosphonate (MDP) or human serum albumin (HSA), to target specific organs or tissues in the body.
Technetium compounds are used in a variety of diagnostic procedures, including bone scans, lung perfusion scans, myocardial perfusion imaging, and brain scans. They provide valuable information about organ function, blood flow, and tissue metabolism, helping doctors diagnose various medical conditions such as cancer, heart disease, and bone fractures.
It is important to note that technetium compounds should only be used under the supervision of trained medical professionals due to their radioactive nature. Proper handling, administration, and disposal procedures must be followed to ensure safety and minimize radiation exposure.
Arsenic is a naturally occurring semi-metal element that can be found in the earth's crust. It has the symbol "As" and atomic number 33 on the periodic table. Arsenic can exist in several forms, including inorganic and organic compounds. In its pure form, arsenic is a steel-gray, shiny solid that is brittle and easily pulverized.
Arsenic is well known for its toxicity to living organisms, including humans. Exposure to high levels of arsenic can cause various health problems, such as skin lesions, neurological damage, and an increased risk of cancer. Arsenic can enter the body through contaminated food, water, or air, and it can also be absorbed through the skin.
In medicine, arsenic has been used historically in the treatment of various diseases, including syphilis and parasitic infections. However, its use as a therapeutic agent is limited due to its toxicity. Today, arsenic trioxide is still used as a chemotherapeutic agent for the treatment of acute promyelocytic leukemia (APL), a type of blood cancer. The drug works by inducing differentiation and apoptosis (programmed cell death) in APL cells, which contain a specific genetic abnormality. However, its use is closely monitored due to the potential for severe side effects and toxicity.
Tartrates are salts or esters of tartaric acid, a naturally occurring organic acid found in many fruits, particularly grapes. In a medical context, potassium bitartrate (also known as cream of tartar) is sometimes used as a mild laxative or to treat acidosis by helping to restore the body's normal pH balance. Additionally, sodium tartrate has been historically used as an antidote for lead poisoning. However, these uses are not common in modern medicine.
Leishmaniasis is a complex of diseases caused by the protozoan parasites of the Leishmania species, which are transmitted to humans through the bite of infected female phlebotomine sandflies. The disease presents with a variety of clinical manifestations, depending upon the Leishmania species involved and the host's immune response.
There are three main forms of leishmaniasis: cutaneous leishmaniasis (CL), mucocutaneous leishmaniasis (MCL), and visceral leishmaniasis (VL), also known as kala-azar. CL typically presents with skin ulcers, while MCL is characterized by the destruction of mucous membranes in the nose, mouth, and throat. VL, the most severe form, affects internal organs such as the spleen, liver, and bone marrow, causing symptoms like fever, weight loss, anemia, and enlarged liver and spleen.
Leishmaniasis is prevalent in many tropical and subtropical regions, including parts of Asia, Africa, South America, and southern Europe. The prevention strategies include using insect repellents, wearing protective clothing, and improving housing conditions to minimize exposure to sandflies. Effective treatment options are available for leishmaniasis, depending on the form and severity of the disease, geographical location, and the Leishmania species involved.
Leishmania is a genus of protozoan parasites that are the causative agents of Leishmaniasis, a group of diseases with various clinical manifestations. These parasites are transmitted to humans through the bite of infected female phlebotomine sandflies. The disease has a wide geographic distribution, mainly in tropical and subtropical regions, including parts of Asia, Africa, South America, and Southern Europe.
The Leishmania species have a complex life cycle that involves two main stages: the promastigote stage, which is found in the sandfly vector, and the amastigote stage, which infects mammalian hosts, including humans. The clinical manifestations of Leishmaniasis depend on the specific Leishmania species and the host's immune response to the infection.
The three main forms of Leishmaniasis are:
1. Cutaneous Leishmaniasis (CL): This form is characterized by skin lesions, such as ulcers or nodules, that can take several months to heal and may leave scars. CL is caused by various Leishmania species, including L. major, L. tropica, and L. aethiopica.
2. Visceral Leishmaniasis (VL): Also known as kala-azar, VL affects internal organs such as the spleen, liver, and bone marrow. Symptoms include fever, weight loss, anemia, and enlarged liver and spleen. VL is caused by L. donovani, L. infantum, and L. chagasi species.
3. Mucocutaneous Leishmaniasis (MCL): This form affects the mucous membranes of the nose, mouth, and throat, causing destruction of tissues and severe disfigurement. MCL is caused by L. braziliensis and L. guyanensis species.
Prevention and control measures for Leishmaniasis include vector control, early diagnosis and treatment, and protection against sandfly bites through the use of insect repellents and bed nets.
Leishmania braziliensis is a species of protozoan parasite that causes American cutaneous leishmaniasis, also known as "espundia." This disease is transmitted to humans through the bite of infected female sandflies, primarily from the genus Lutzomyia. The infection can lead to skin lesions, ulcers, and scarring, and in some cases, it can disseminate and affect other organs, causing a more severe form of the disease called mucocutaneous leishmaniasis.
The parasite's life cycle involves two main stages: the promastigote stage, which occurs in the sandfly vector, and the amastigote stage, which takes place inside the mammalian host's macrophages. The infection can be diagnosed through various methods, including microscopic examination of tissue samples, culture isolation, or molecular techniques such as PCR. Treatment typically involves antiparasitic drugs, such as pentavalent antimonials, amphotericin B, or miltefosine, depending on the severity and location of the infection.
Neutron Activation Analysis (NAA) is not strictly a medical definition, but it's a technique used in the field of nuclear medicine and forensic medicine for material analysis and identification. Here's a general definition:
Neutron Activation Analysis is a non-destructive analytical method that uses nuclear reactions to identify and determine the concentration of elements within a sample. The sample is irradiated with neutrons, which induce nuclear reactions that produce radioactive isotopes of the elements present in the sample. The gamma radiation emitted by these radioisotopes is then measured and analyzed to quantify the elemental composition of the sample. This technique is particularly useful for detecting and measuring trace elements and isotopes, making it valuable in various fields such as archaeology, geology, nuclear medicine, and forensic science.
Mucocutaneous Leishmaniasis (MCL) is a chronic, granulomatous disease caused by an infection with Leishmania species, primarily L. braziliensis and L. guyanensis. It affects both the mucous membranes (such as those of the nose, mouth, and throat) and the skin.
The initial infection often occurs through the bite of an infected female sandfly, which transmits the parasitic protozoa into the host's skin. After a variable incubation period, the disease can manifest in different clinical forms, including localized cutaneous leishmaniasis (CL), disseminated cutaneous leishmaniasis, and mucocutaneous leishmaniasis.
MCL is characterized by progressive destruction of the mucous membranes, leading to deformities and functional impairments. The infection typically starts as a cutaneous lesion at the site of the sandfly bite, which heals spontaneously within several months. However, in some cases, the parasites disseminate to the mucous membranes, causing severe inflammation, ulceration, and tissue necrosis.
Symptoms of MCL include:
1. Destruction of nasal septum, leading to a saddle-nose deformity
2. Perforation of the palate or septum
3. Hoarseness or loss of voice due to laryngeal involvement
4. Difficulty swallowing and speaking
5. Chronic rhinitis, sinusitis, or otitis media
6. Severe disfigurement and functional impairments in advanced cases
Diagnosis is usually made by identifying the parasites in tissue samples (such as biopsies) using microscopy, culture, or PCR-based methods. Treatment typically involves systemic antiparasitic drugs, such as pentavalent antimonials, amphotericin B, miltefosine, or combination therapies, along with surgical interventions to reconstruct damaged tissues in advanced cases.
Drug resistance, also known as antimicrobial resistance, is the ability of a microorganism (such as bacteria, viruses, fungi, or parasites) to withstand the effects of a drug that was originally designed to inhibit or kill it. This occurs when the microorganism undergoes genetic changes that allow it to survive in the presence of the drug. As a result, the drug becomes less effective or even completely ineffective at treating infections caused by these resistant organisms.
Drug resistance can develop through various mechanisms, including mutations in the genes responsible for producing the target protein of the drug, alteration of the drug's target site, modification or destruction of the drug by enzymes produced by the microorganism, and active efflux of the drug from the cell.
The emergence and spread of drug-resistant microorganisms pose significant challenges in medical treatment, as they can lead to increased morbidity, mortality, and healthcare costs. The overuse and misuse of antimicrobial agents, as well as poor infection control practices, contribute to the development and dissemination of drug-resistant strains. To address this issue, it is crucial to promote prudent use of antimicrobials, enhance surveillance and monitoring of resistance patterns, invest in research and development of new antimicrobial agents, and strengthen infection prevention and control measures.
Arsenites are inorganic compounds that contain arsenic in the trivalent state (arsenic-III). They are formed by the reaction of arsenic trioxide (As2O3) or other trivalent arsenic compounds with bases such as sodium hydroxide, potassium hydroxide, or ammonia.
The most common and well-known arsenite is sodium arsenite (NaAsO2), which has been used in the past as a wood preservative and pesticide. However, due to its high toxicity and carcinogenicity, its use has been largely discontinued. Other examples of arsenites include potassium arsenite (KAsO2) and calcium arsenite (Ca3(AsO3)2).
Arsenites are highly toxic and can cause a range of health effects, including skin irritation, nausea, vomiting, diarrhea, abdominal pain, and death in severe cases. Long-term exposure to arsenites has been linked to an increased risk of cancer, particularly lung, bladder, and skin cancer.
Ion pumps, also known as ion transporters, are membrane-bound proteins that actively transport ions across a biological membrane against their electrochemical gradient. This process requires energy, usually in the form of ATP (adenosine triphosphate), and allows cells to maintain resting potentials, regulate intracellular ion concentrations, and facilitate various physiological processes such as nerve impulse transmission, muscle contraction, and cell volume regulation.
Ion pumps can transport one or more types of ions, including sodium (Na+), potassium (K+), chloride (Cl-), calcium (Ca2+), and protons (H+). A well-known example of an ion pump is the Na+/K+ ATPase, which transports three sodium ions out of the cell and two potassium ions into the cell for each ATP molecule hydrolyzed. This creates a concentration gradient that drives the passive transport of Na+ and K+ ions through other channels, contributing to the resting membrane potential.
Arsenite transporting ATPases are a type of membrane-bound enzyme complexes that use the energy from ATP hydrolysis to actively transport arsenic compounds across cell membranes. They are part of the P-type ATPase family and play a crucial role in detoxifying cells by removing arsenite (AsIII) ions, which are highly toxic even at low concentrations.
These enzymes consist of two main domains: a cytoplasmic domain responsible for ATP binding and hydrolysis, and a transmembrane domain that contains the ion transport pathway. The transport process involves several conformational changes in the protein structure, driven by ATP hydrolysis, which ultimately result in the movement of arsenite ions against their concentration gradient from the cytoplasm to the extracellular space or into organelles like vacuoles and endosomes.
In humans, there are two main isoforms of arsenite transporting ATPases: ACR3 (also known as ARS-A) and ACR2 (or ARS-B). Both isoforms have been identified in various tissues, including the liver, kidney, and intestine. Mutations in these genes can lead to impaired arsenic detoxification and increased susceptibility to arsenic toxicity.
Overall, arsenite transporting ATPases are essential for maintaining cellular homeostasis and protecting organisms from the harmful effects of environmental arsenic exposure.