| 1 |
What is hybrid micellar liquid chromatography primarily used for in the study?
|
To detect commonly used pesticides in vegetables. |
|
The study utilized **Hybrid Micellar Liquid Chromatography (HMLC)** as a core analytical technique because it aligns with **Green Analytical Chemistry (GAC)** principles. HMLC reduces the reliance on toxic organic solvents by incorporating micelles in the mobile phase and enables direct sample injection, thereby minimizing solvent waste and streamlining the preparation process. The primary use of this green method was to accurately detect and quantify common pesticide residues —such as high levels of Chlorpyrifos—in green leafy vegetables from Sagar, India. These findings are critically important as they provide essential data on agricultural contamination, highlighting significant food safety concerns and the urgent need for informed regulatory intervention. |
Nevertheless, a hybrid micellar liquid chromatography (HMLC) can also be used. HMLC is a modified version of the high-performance liquid chromatographic (HPLC) technique, where the composition of the mobile phase is a modified aqueous micellar mobile phase with a major part of water, surfactant (above critical micellar concentration) and low concentration of short-chain alcohols (i.e., 1-propanol, 1-butanol, 1-pentanol) as an organic modifier. This change in the HMLC method facilitates the injection of extracts from the real samples after simple filtration onto the chromatographic column. This saves time and money consumed in the stepwise extraction process for sample pre-treatment and reduces environmental pollution caused by bulk organic solvents in conventional chromatographic methods [22,23]. For this reason, HMLC can be considered a green analytical method according to the indications given by National Environmental Method Index (NEMI), Green Analytical Procedure Index (GAPI) and Analytical Eco-Scale. Furthermore, this green technique has been successfully used to determine ICP in fruit juices.
In this study, a hybrid HMLC-PDA method was developed and validated for simultaneous separation and detection of ICP, CPS, PFF and CP in green leafy vegetables, which are the most common pesticides used in Sagar, underdeveloped, drought-prone area of Bundelkhand region of Madhya Pradesh in central India.
Therefore, the analytical method has made it possible to understand if there is a correlation between the obtained data and the information collected from those who produce and use the substance. This research article presents a method that belongs to the green analytical approach in chromatography. The methods used low toxicity solvents and waste in post-analysis is also reduced. These factors are very important for environmental conditions and the development of a low-cost and green method, which can be fundamental for those laboratories in underdeveloped and developing countries From Science Direct Detection of most commonly used pesticides in green leafy vegetables from sagar, india using direct injection hybrid micellar liquid chromatography |
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| 2 |
Which pesticide was found most commonly in the vegetable samples?
|
Chlorpyrifos |
|
Chlorpyrifos was the most common pesticide detected (76% of samples), driven by grower preference for its low cost and high efficacy. This extreme prevalence is a significant public health concern due to the pesticide's neurotoxicity, demanding immediate regulatory intervention and a shift toward safer agricultural practices. |
.1. Pesticide survey and data collection
2.1.1. The survey from vegetable growers
This study was carried out in Sagar (M.P.), India. Insecticide application-related information on leafy vegetables was collected from vegetable growers. Forty (40) vegetable growers were interviewed and considered representative of local vegetable growers who come in the periphery of 20 km from the Sagar city center. The distance was defined because leafy vegetables have a short lifetime and it was challenging to transport them from long distances. The survey of vegetable growers and pesticide dealers was conducted by direct interview method (questionnaire) in regional language. Information regarding types of leafy vegetables, the pesticide used, application rate per square meter (sqm), time of harvesting, frequency of harvesting etc. were collected.
2.1.2. The survey from pesticide dealers
The pesticide dealers of Sagar city were also interviewed. Ten local pesticide dealers who cover the major part of the city in pesticide distribution were interviewed. Information was collected about pesticides, which are currently in trend for application on green leafy vegetables, their daily selling prices, effectiveness on target insects, instructions and recommendations for their customers about pesticide management etc. The dealer survey was conducted to check whether vegetable growers followed the instructions given by the dealer or not.
2.2. Sample collection
Green leafy vegetable samples were collected during the winter season from four main vegetable markets of Sagar city i.e., Main mandi, Makronia bajariya, Bada bazar and Tilli road (Fig. 1). These four vegetable markets are the hub, where fresh vegetables arrive every day and from where retailers purchase the vegetables to be sold at the local level. Six types of leafy vegetable samples and two of each type were collected from the four main vegetable markets which are mentioned above. The vegetables included leaves of spinach (Spinacia oleracea L.), fenugreek (Trigonella foenumgraecum L.), chickpea (Cicer arietinum L.), onion (Allium cepa L.), mustard (Brassica juncea L.) and coriander (Coriandrum sativum L.). Therefore a total of 48 samples of the green leafy vegetables were collected. These vegetables were selected since they are the main leafy vegetables consumed in this region during the winter seasonFrom Science Direct Detection of most commonly used pesticides in green leafy vegetables from sagar, india using direct injection hybrid micellar liquid chromatography |
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| 3 |
What percentage of the vegetable samples tested were found to contain no detectable pesticides?
|
16% |
|
A total of 16% of the vegetable samples tested were found to be negative, meaning they contained no detectable residues of the four targeted pesticides. Conversely, the vast majority of samples 84% did contain residues of at least one pesticide. |
2.1. Pesticide survey and data collection
2.1.1. The survey from vegetable growers
This study was carried out in Sagar (M.P.), India. Insecticide application-related information on leafy vegetables was collected from vegetable growers. Forty (40) vegetable growers were interviewed and considered representative of local vegetable growers who come in the periphery of 20 km from the Sagar city center. The distance was defined because leafy vegetables have a short lifetime and it was challenging to transport them from long distances. The survey of vegetable growers and pesticide dealers was conducted by direct interview method (questionnaire) in regional language. Information regarding types of leafy vegetables, the pesticide used, application rate per square meter (sqm), time of harvesting, frequency of harvesting etc. were collected.
2.1.2. The survey from pesticide dealers
The pesticide dealers of Sagar city were also interviewed. Ten local pesticide dealers who cover the major part of the city in pesticide distribution were interviewed. Information was collected about pesticides, which are currently in trend for application on green leafy vegetables, their daily selling prices, effectiveness on target insects, instructions and recommendations for their customers about pesticide management etc. The dealer survey was conducted to check whether vegetable growers followed the instructions given by the dealer or not.From Science Direct Detection of most commonly used pesticides in green leafy vegetables from sagar, india using direct injection hybrid micellar liquid chromatography |
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| 4 |
Which of the following is NOT a reason for the use of hybrid micellar liquid chromatography (HMLC)?
|
It requires extensive solvent use. |
|
The incorrect reason is that **it requires extensive solvent use.**
Hybrid Micellar Liquid Chromatography (HMLC) is valued because it is a green analytical method that specifically aims to reduce or eliminate extensive solvent use It achieves this by replacing most of the toxic organic solvents in the mobile phase with aqueous-basedmicelles, making the method safer, cheaper, and more eco-friendly. |
.1. Pesticide survey and data collection
2.1.1. The survey from vegetable growers
This study was carried out in Sagar (M.P.), India. Insecticide application-related information on leafy vegetables was collected from vegetable growers. Forty (40) vegetable growers were interviewed and considered representative of local vegetable growers who come in the periphery of 20 km from the Sagar city center. The distance was defined because leafy vegetables have a short lifetime and it was challenging to transport them from long distances. The survey of vegetable growers and pesticide dealers was conducted by direct interview method (questionnaire) in regional language. Information regarding types of leafy vegetables, the pesticide used, application rate per square meter (sqm), time of harvesting, frequency of harvesting etc. were collected.
2.1.2. The survey from pesticide dealers
The pesticide dealers of Sagar city were also interviewed. Ten local pesticide dealers who cover the major part of the city in pesticide distribution were interviewed. Information was collected about pesticides, which are currently in trend for application on green leafy vegetables, their daily selling prices, effectiveness on target insects, instructions and recommendations for their customers about pesticide management etc. The dealer survey was conducted to check whether vegetable growers followed the instructions given by the dealer or not. |
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| 5 |
What was the primary methodological change in the HMLC technique used in the study?
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Use of a micellar mobile phase with reduced solvent usage. |
|
HMLC's core change is replacing large amounts of toxic organic solvents with a mobile phase primarily composed of water and surfactant micelles. This switch makes the method significantly "greener" by cutting solvent consumption |
2.5. Chromatographic conditions instruments and software processing
The HMLC system used for the analysis was from Shimadzu Corporation (Shimadzu Prominence), Kyoto (Japan), having LC-20 AT isocratic pump, SIL-20AC auto-sampler, a photodiode array detector (SPD-M20A, 190–800 nm) and a Shimadzu C18 analytical column (250 mm length × 4.6 mm with 5 µm particle size), injection volume 20 µL. Isocratic elution using the aqueous micellar mobile at a flow of 1 mL/min., was used to separate the analytes. Data acquisition and elaboration were performed by the software Shimadzu LC Solution software version 1.22 SP1. The maximum absorbance for ICP was 270 nm, for CPS was 266 nm, PFF was 253 nm and CP was 244 nm.
Analytical balance Mettler-Toledo ME204 (Pocklington, United Kingdom) weighed the standards and incurred samples. Magnetic stirrer and the ultrasonic bath were purchased from PCI Analytics (Mumbai, India). Measurements of pH were performed using a Contech LAB pH meter, Model pH-103 (Mumbai, India).
All tables, charts, chromatograms and diagrams were made using the software MS Excel, MS Powerpoint, Origin Pro 2018 and Biorender. |
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| 6 |
According to the study, why might vegetable growers prefer other pesticides over Imidacloprid (ICP)?
|
ICP is less effective on pests. |
|
Growers perceive Imidacloprid (ICP) as less effective than cheaper, older organophosphates (like Chlorpyrifos) because the organophosphates provide a more rapid, visible knockdown effect against a broad spectrum of pests. This perceived reduced efficacy of ICP makes growers concerned that they would need to apply it more frequently, making the overall pest control strategy less reliable and cost-effective than the immediate results offered by the more toxic alternatives. |
Introduction
Today green leafy vegetables are considered a good source of essential vitamins, minerals, and antioxidants, making them an integral component of a daily vegetarian diet [1,2]. Green leafy vegetables are more sensitive to changes in environmental conditions as well as are prone to frequent attacks by the pest. Greenhouses can be used to overcome the adverse effect on the environment, whereas pesticides are generally used to save vegetables from the attack of pests. The most common pesticides used on green leafy vegetables are monocrotophos (MONO), dichlorvos (DCV), chlorpyrifos (CPS), profenofos (PFF), cypermethrin (CP) etc.
Pesticides provide a vital benefit to agricultural production but at the same time, they may pose severe health issues for farmers and consumers of these agricultural products. In India, with changing agricultural practices, the consumption of pesticides has significantly increased. The excessive use of these pesticides is quite evident due to their presence in vegetables, animal feeds [3], food products [4], packed food [5] and even in human breast milk [6] and they can have serious health effects [7,8]. Pesticides show their toxic effects acutely and chronically. Common acute effects are vomiting, nausea, convulsions, rashes, blisters, blindness, dizziness, diarrhea, death, etc. In contrast, chronic effects include cancer, neuro-diseases (acetylcholinesterase inhibition, Parkinson's disorder), endocrinal disruption, diabetes, leukaemia, asthma and so on [9,10].
Traditional pesticides like CPS, PFF and CP, MONO, DCV have high efficiency in controlling insects for safety purposes and they fall in the 'Class I' type of pesticides. The EPA banned some of them like MONO or DCV in developing countries, including India. Nevertheless, in India, these pesticides are still being used on vegetables and fruits [10,11,12] because no legislation has been implemented to determine the maximum permissible concentration of pesticides in vegetables.
In recent years imidacloprid (ICP) an insecticide that belongs to the class of neonicotinoids (NN) is among the most commonly used in agriculture. The mode of action and chemical structure of ICP is similar to nicotine with a toxicity 700 folds lower than nicotine [13]. Therefore ICP can be considered a good alternative for those pesticides which cause toxicity.
Several studies to detect ICP, CPS, PFF and CP in green leafy vegetables [14], fruit juices [15] and foods [16] were conducted using different chromatographic methods; high-performance liquid chromatography coupled to diode array detector (HPLC-DAD) [16], gas chromatography coupled to mss spectrometry (GC–MS) [17,18,19], liquid chromatography coupled to mass spectrometry (LC-MS/MS) [20,21]. Nevertheless, a hybrid micellar liquid chromatography (HMLC) can also be used. HMLC is a modified version of the high-performance liquid chromatographic (HPLC) technique, where the composition of the mobile phase is a modified aqueous micellar mobile phase with a major part of water, surfactant (above critical micellar concentration) and low concentration of short-chain alcohols (i.e., 1-propanol, 1-butanol, 1-pentanol) as an organic modifier. This change in the HMLC method facilitates the injection of extracts from the real samples after simple filtration onto the chromatographic column. This saves time and money consumed in the stepwise extraction process for sample pre-treatment and reduces environmental pollution caused by bulk organic solvents in conventional chromatographic methods [22,23]. For this reason, HMLC can be considered a green analytical method according to the indications given by National Environmental Method Index (NEMI), Green Analytical Procedure Index (GAPI) and Analytical Eco-Scale. Furthermore, this green technique has been successfully used to determine ICP in fruit juices.
In this study, a hybrid HMLC-PDA method was developed and validated for simultaneous separation and detection of ICP, CPS, PFF and CP in green leafy vegetables, which are the most common pesticides used in Sagar, underdeveloped, drought-prone area of Bundelkhand region of Madhya Pradesh in central India.
Therefore, the analytical method has made it possible to understand if there is a correlation between the obtained data and the information collected from those who produce and use the substance. This research article presents a method that belongs to the green analytical approach in chromatography. The methods used low toxicity solvents and waste in post-analysis is also reduced. These factors are very important for environmental conditions and the development of a low-cost and green method, which can be fundamental for those laboratories in underdeveloped and developing countries. |
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| 7 |
What is the major benefit of using ICP as a pesticide, according to the study?
|
It is less toxic compared to many others. |
|
The major benefit of Imidacloprid (ICP) is that it is less toxic compared to the older, hazardous organophosphates (like Chlorpyrifos) that growers currently prefer. |
Abstract
Imidacloprid, chlorpyrifos, profenofos and cypermethrin are most commonly applied pesticides on green leafy vegetables. After a survey conducted to know the pesticide management practices in Sagar, India, a procedure based on hybrid micellar liquid chromatography coupled to a photodiode array detector has been developed and validated to monitor imidacloprid, chlorpyrifos, profenofos and cypermethrin content in green leafy vegetables. The method was validated following the guideline of SANTE/11,312/2021 in terms of: selectivity, linearity (r2> 0.998), limit of quantification (0.09–0.25 mg/Kg, depending on the analyte under investigation), precision (<8.1%), and robustness (<5%). Chlorpyrifos was found to be the most commonly used pesticide among vegetable growers. It was found in seventy-six percent samples, profenofos in fifty-one percent, imidacloprid in eight percent and cypermethrin in four percent of the analyzed green leafy vegetable sample either individually or in combination. Sixteen percent of the collected samples were found to be negative for the selected pesticides. The developed procedure is rapid, easy to handle, green since it uses a low amount of toxic chemicals providing reliable results. The method was used to evaluate the eventual correlation between the analytical data and the information collected from the producers and users of these pesticides. |
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| 8 |
What aspect of the pesticide detection method was focused on during the method validation phase?
|
Ensuring it can detect extremely low pesticide levels. |
|
Validation established the method was fit for purpose by confirming its ability to reliably measure minute pesticide residues, which is demonstrated by determining the Limits of Detection (LOD) and Quantification (LOQ) |
2. Materials and methods
2.1. Pesticide survey and data collection
2.1.1. The survey from vegetable growers
This study was carried out in Sagar (M.P.), India. Insecticide application-related information on leafy vegetables was collected from vegetable growers. Forty (40) vegetable growers were interviewed and considered representative of local vegetable growers who come in the periphery of 20 km from the Sagar city center. The distance was defined because leafy vegetables have a short lifetime and it was challenging to transport them from long distances. The survey of vegetable growers and pesticide dealers was conducted by direct interview method (questionnaire) in regional language. Information regarding types of leafy vegetables, the pesticide used, application rate per square meter (sqm), time of harvesting, frequency of harvesting etc. were collected.
2.1.2. The survey from pesticide dealers
The pesticide dealers of Sagar city were also interviewed. Ten local pesticide dealers who cover the major part of the city in pesticide distribution were interviewed. Information was collected about pesticides, which are currently in trend for application on green leafy vegetables, their daily selling prices, effectiveness on target insects, instructions and recommendations for their customers about pesticide management etc. The dealer survey was conducted to check whether vegetable growers followed the instructions given by the dealer or not. |
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-.25
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| 9 |
Considering the environmental impacts discussed, why is the HMLC method considered 'green'?
|
It involves less waste and uses low-toxicity solvents. |
|
The method is green as it replaces most toxic organic solvents with an aqueous micellar mobile phase, drastically cutting down on hazardous chemical waste production. |
Introduction
Today green leafy vegetables are considered a good source of essential vitamins, minerals, and antioxidants, making them an integral component of a daily vegetarian diet [1,2]. Green leafy vegetables are more sensitive to changes in environmental conditions as well as are prone to frequent attacks by the pest. Greenhouses can be used to overcome the adverse effect on the environment, whereas pesticides are generally used to save vegetables from the attack of pests. The most common pesticides used on green leafy vegetables are monocrotophos (MONO), dichlorvos (DCV), chlorpyrifos (CPS), profenofos (PFF), cypermethrin (CP) etc.
Pesticides provide a vital benefit to agricultural production but at the same time, they may pose severe health issues for farmers and consumers of these agricultural products. In India, with changing agricultural practices, the consumption of pesticides has significantly increased. The excessive use of these pesticides is quite evident due to their presence in vegetables, animal feeds [3], food products [4], packed food [5] and even in human breast milk [6] and they can have serious health effects [7,8]. Pesticides show their toxic effects acutely and chronically. Common acute effects are vomiting, nausea, convulsions, rashes, blisters, blindness, dizziness, diarrhea, death, etc. In contrast, chronic effects include cancer, neuro-diseases (acetylcholinesterase inhibition, Parkinson's disorder), endocrinal disruption, diabetes, leukaemia, asthma and so on [9,10].
Traditional pesticides like CPS, PFF and CP, MONO, DCV have high efficiency in controlling insects for safety purposes and they fall in the 'Class I' type of pesticides. The EPA banned some of them like MONO or DCV in developing countries, including India. Nevertheless, in India, these pesticides are still being used on vegetables and fruits [10,11,12] because no legislation has been implemented to determine the maximum permissible concentration of pesticides in vegetables.
In recent years imidacloprid (ICP) an insecticide that belongs to the class of neonicotinoids (NN) is among the most commonly used in agriculture. The mode of action and chemical structure of ICP is similar to nicotine with a toxicity 700 folds lower than nicotine [13]. Therefore ICP can be considered a good alternative for those pesticides which cause toxicity.
Several studies to detect ICP, CPS, PFF and CP in green leafy vegetables [14], fruit juices [15] and foods [16] were conducted using different chromatographic methods; high-performance liquid chromatography coupled to diode array detector (HPLC-DAD) [16], gas chromatography coupled to mss spectrometry (GC–MS) [17,18,19], liquid chromatography coupled to mass spectrometry (LC-MS/MS) [20,21]. Nevertheless, a hybrid micellar liquid chromatography (HMLC) can also be used. HMLC is a modified version of the high-performance liquid chromatographic (HPLC) technique, where the composition of the mobile phase is a modified aqueous micellar mobile phase with a major part of water, surfactant (above critical micellar concentration) and low concentration of short-chain alcohols (i.e., 1-propanol, 1-butanol, 1-pentanol) as an organic modifier. This change in the HMLC method facilitates the injection of extracts from the real samples after simple filtration onto the chromatographic column. This saves time and money consumed in the stepwise extraction process for sample pre-treatment and reduces environmental pollution caused by bulk organic solvents in conventional chromatographic methods [22,23]. For this reason, HMLC can be considered a green analytical method according to the indications given by National Environmental Method Index (NEMI), Green Analytical Procedure Index (GAPI) and Analytical Eco-Scale. Furthermore, this green technique has been successfully used to determine ICP in fruit juices.
In this study, a hybrid HMLC-PDA method was developed and validated for simultaneous separation and detection of ICP, CPS, PFF and CP in green leafy vegetables, which are the most common pesticides used in Sagar, underdeveloped, drought-prone area of Bundelkhand region of Madhya Pradesh in central India.
Therefore, the analytical method has made it possible to understand if there is a correlation between the obtained data and the information collected from those who produce and use the substance. This research article presents a method that belongs to the green analytical approach in chromatography. The methods used low toxicity solvents and waste in post-analysis is also reduced. These factors are very important for environmental conditions and the development of a low-cost and green method, which can be fundamental for those laboratories in underdeveloped and developing countries. |
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| 10 |
What is the importance of the photodiode array detector in the HMLC technique used in the study?
|
It detects the presence of pesticides across a spectrum of wavelengths. |
|
The PDA detector is crucial for confirmation and selectivity. It captures the full UV-Vis absorption spectrum of a compound as it elutes, allowing researchers to confirm the identity of a pesticide residue by matching its unique spectral fingerprint against known standards. |
Materials and methods
2.1. Pesticide survey and data collection
2.1.1. The survey from vegetable growers
This study was carried out in Sagar (M.P.), India. Insecticide application-related information on leafy vegetables was collected from vegetable growers. Forty (40) vegetable growers were interviewed and considered representative of local vegetable growers who come in the periphery of 20 km from the Sagar city center. The distance was defined because leafy vegetables have a short lifetime and it was challenging to transport them from long distances. The survey of vegetable growers and pesticide dealers was conducted by direct interview method (questionnaire) in regional language. Information regarding types of leafy vegetables, the pesticide used, application rate per square meter (sqm), time of harvesting, frequency of harvesting etc. were collected.
2.1.2. The survey from pesticide dealers
The pesticide dealers of Sagar city were also interviewed. Ten local pesticide dealers who cover the major part of the city in pesticide distribution were interviewed. Information was collected about pesticides, which are currently in trend for application on green leafy vegetables, their daily selling prices, effectiveness on target insects, instructions and recommendations for their customers about pesticide management etc. The dealer survey was conducted to check whether vegetable growers followed the instructions given by the dealer or not.
2.2. Sample collection
Green leafy vegetable samples were collected during the winter season from four main vegetable markets of Sagar city i.e., Main mandi, Makronia bajariya, Bada bazar and Tilli road (Fig. 1). These four vegetable markets are the hub, where fresh vegetables arrive every day and from where retailers purchase the vegetables to be sold at the local level. Six types of leafy vegetable samples and two of each type were collected from the four main vegetable markets which are mentioned above. The vegetables included leaves of spinach (Spinacia oleracea L.), fenugreek (Trigonella foenumgraecum L.), chickpea (Cicer arietinum L.), onion (Allium cepa L.), mustard (Brassica juncea L.) and coriander (Coriandrum sativum L.). Therefore a total of 48 samples of the green leafy vegetables were collected. These vegetables were selected since they are the main leafy vegetables consumed in this region during the winter season. |
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| 11 |
What is hyperthermia commonly used to treat?
|
Cancer |
|
Hyperthermia is like giving chemo and radiation a super boost. The heat makes the cancer cells weaker and easier for the regular treatments to kill. |
Hyperthermia: Role and Risk Factor for Cancer TreatmentAbstract
Over the past decades, cancer is the major cause of incidence of death increasing every day. Different forms of tumor therapy including radiotherapy and chemotherapy are used to treat cancer. However, hyperthermia is the technique that neglects the use of chemicals or harmful radiations. The elevated body temperature can damage the cancerous cells with minimum injury to the normal cells. Successful therapy method in combination with radiation therapy and/or chemotherapy is provided to the cancer patient which proved to be beneficial to the patients. In this review, different studies of the clinical trials are reported on the patients with tumor and the therapy associated with it.
|
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| 12 |
Which method is used to apply heat directly to a tumor in local hyperthermia?
|
Microwaves |
|
Think of it like a tiny, focused microwave oven aimed right at the tumor. We use microwaves (or similar energy like radio waves) to heat the cancer cells directly and kill them on the spot without harming the surrounding area too much. |
Abstract
Over the past decades, cancer is the major cause of incidence of death increasing every day. Different forms of tumor therapy including radiotherapy and chemotherapy are used to treat cancer. However, hyperthermia is the technique that neglects the use of chemicals or harmful radiations. The elevated body temperature can damage the cancerous cells with minimum injury to the normal cells. Successful therapy method in combination with radiation therapy and/or chemotherapy is provided to the cancer patient which proved to be beneficial to the patients. In this review, different studies of the clinical trials are reported on the patients with tumor and the therapy associated with it.
|
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| 13 |
Which method is used to apply heat directly to a tumor in local hyperthermia?
|
Microwaves |
|
Think of it like a tiny, focused microwave oven aimed right at the tumor. We use microwaves (or similar energy like radio waves) to heat the cancer cells directly and kill them on the spot without harming the surrounding area too much. |
Abstract
Over the past decades, cancer is the major cause of incidence of death increasing every day. Different forms of tumor therapy including radiotherapy and chemotherapy are used to treat cancer. However, hyperthermia is the technique that neglects the use of chemicals or harmful radiations. The elevated body temperature can damage the cancerous cells with minimum injury to the normal cells. Successful therapy method in combination with radiation therapy and/or chemotherapy is provided to the cancer patient which proved to be beneficial to the patients. In this review, different studies of the clinical trials are reported on the patients with tumor and the therapy associated with it.
|
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| 14 |
Hyperthermia is often used in combination with which of the following treatments?
|
Radiotherapy and chemotherapy |
|
It's used with radiotherapy and chemo because the heat makes the cancer cells weaker. Think of it as softening up the target so the radiation and drugs can kill the cancer much more effectively. |
Abstract
Over the past decades, cancer is the major cause of incidence of death increasing every day. Different forms of tumor therapy including radiotherapy and chemotherapy are used to treat cancer. However, hyperthermia is the technique that neglects the use of chemicals or harmful radiations. The elevated body temperature can damage the cancerous cells with minimum injury to the normal cells. Successful therapy method in combination with radiation therapy and/or chemotherapy is provided to the cancer patient which proved to be beneficial to the patients. In this review, different studies of the clinical trials are reported on the patients with tumor and the therapy associated with it. |
7 |
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| 15 |
What is the main challenge of using hyperthermia in cancer treatment?
|
There is no scientific evidence to support its effectiveness. |
|
This claim lacks scientific support because :It contradicts extensive oncological literature on cancer cell biology and metastasis.The mechanism (cells being "shocked into submission") is non-specific and has no established biological pathway.It claims a 100% cure rate with minimal treatment, which is not supported by rigorous clinical trials or long-term survival data. |
ntroduction
Hyperthermia (also known as thermotherapy) is generally regarded as a mean body temperature higher than normal (Alexander, 2008). High body temperature is often caused by illness, such as fever or heat stroke. Research has shown that elevated body temperature can damage and kill cancerous cells with minimal injury to normal cells (van der Zee et al., 2000). The main mechanism involved is by killing the cancer cells by destructing proteins and the structure within cells. Thus, hyperthermia may shrink tumors (Wust et al., 2002). Hyperthermia may make some of the tumor cells more prone to radiations or damage other cancer cells which cannot be damaged by radiation. Many times, it also increases the effects of certain anticancer agents. In this study, we would focus on use of heat to treat cancer. Hyperthermia is widely applicable with different other forms of cancer therapy, including radiation therapy and chemotherapy (Alexander, 2001). The aim of the study was to treat many types of cancer including brain, liver, sarcoma, lung, esophagus, breast, bladder, rectum and peritoneal lining (Kapp et al., 1990, Van der Zee et al., 2000). There are over 100 types of cancers present in the world and are classified according to cell type. According to GLOBOCAN statistics analysis (2012), 14.1 million new cancer cases, 8.2 million cancer deaths and 32.6 million people living with Cancer were reported (Ferlay et al., 2013). The American Cancer society in 2014 provided the annual report, according to which there will be an estimated 1,665,540 new cancer cases diagnosed (ACS). Hyperthermia is under clinical trials (research study with people) and is not widely available. However, while receiving those combination therapies, only few have shown increased survival in patients (Falk and Issels, 2001). Various techniques of hyperthermia are presently under investigation, that include local, regional and whole body hyperthermia (Feldman et al., 2003, Chang et al., 2001). Many of these have shown a significant depression in tumor size when hyperthermia is combined with other treatment or therapy. Attaining temperature above the systemic temperature 37 °C in a specified target volume is a challenge and still under development. High temperature is induced by applying a power density specific absorption rate (SAR; measured in W/kg). Normal basal metabolism of human is above 1 W/kg. Perfusion counteracts the elevated temperature. In humans perfusion rate is around 5–15 ml per 100 g per min, but they differ widely. To reach the elevated temperature approx 42 °C at least in some parts of the body tumors require a power density of approx 20–40 W/kg at the target region (Tilly et al., 2001). (See Table 1, Table 2.) |
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| 16 |
Which type of hyperthermia involves heating a larger region or the whole body?
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Whole-body hyperthermia |
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This procedure is used to raise the patient's entire body temperature, mimicking a fever. It is typically used for cancer that has spread (metastasized) throughout the body, aiming to make all cancer cells more susceptible to chemotherapy or immunotherapy. |
Introduction
Hyperthermia (also known as thermotherapy) is generally regarded as a mean body temperature higher than normal (Alexander, 2008). High body temperature is often caused by illness, such as fever or heat stroke. Research has shown that elevated body temperature can damage and kill cancerous cells with minimal injury to normal cells (van der Zee et al., 2000). The main mechanism involved is by killing the cancer cells by destructing proteins and the structure within cells. Thus, hyperthermia may shrink tumors (Wust et al., 2002). Hyperthermia may make some of the tumor cells more prone to radiations or damage other cancer cells which cannot be damaged by radiation. Many times, it also increases the effects of certain anticancer agents. In this study, we would focus on use of heat to treat cancer. Hyperthermia is widely applicable with different other forms of cancer therapy, including radiation therapy and chemotherapy (Alexander, 2001). The aim of the study was to treat many types of cancer including brain, liver, sarcoma, lung, esophagus, breast, bladder, rectum and peritoneal lining (Kapp et al., 1990, Van der Zee et al., 2000). There are over 100 types of cancers present in the world and are classified according to cell type. According to GLOBOCAN statistics analysis (2012), 14.1 million new cancer cases, 8.2 million cancer deaths and 32.6 million people living with Cancer were reported (Ferlay et al., 2013). The American Cancer society in 2014 provided the annual report, according to which there will be an estimated 1,665,540 new cancer cases diagnosed (ACS). Hyperthermia is under clinical trials (research study with people) and is not widely available. However, while receiving those combination therapies, only few have shown increased survival in patients (Falk and Issels, 2001). Various techniques of hyperthermia are presently under investigation, that include local, regional and whole body hyperthermia (Feldman et al., 2003, Chang et al., 2001). Many of these have shown a significant depression in tumor size when hyperthermia is combined with other treatment or therapy. Attaining temperature above the systemic temperature 37 °C in a specified target volume is a challenge and still under development. High temperature is induced by applying a power density specific absorption rate (SAR; measured in W/kg). Normal basal metabolism of human is above 1 W/kg. Perfusion counteracts the elevated temperature. In humans perfusion rate is around 5–15 ml per 100 g per min, but they differ widely. To reach the elevated temperature approx 42 °C at least in some parts of the body tumors require a power density of approx 20–40 W/kg at the target region (Tilly et al., 2001). (See Table 1, Table 2.) |
7 |
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0
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| 17 |
What type of hyperthermia uses applicators inserted into or near a body cavity to deliver heat?
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Endocavitary hyperthermia |
|
|
Introduction
Hyperthermia (also known as thermotherapy) is generally regarded as a mean body temperature higher than normal (Alexander, 2008). High body temperature is often caused by illness, such as fever or heat stroke. Research has shown that elevated body temperature can damage and kill cancerous cells with minimal injury to normal cells (van der Zee et al., 2000). The main mechanism involved is by killing the cancer cells by destructing proteins and the structure within cells. Thus, hyperthermia may shrink tumors (Wust et al., 2002). Hyperthermia may make some of the tumor cells more prone to radiations or damage other cancer cells which cannot be damaged by radiation. Many times, it also increases the effects of certain anticancer agents. In this study, we would focus on use of heat to treat cancer. Hyperthermia is widely applicable with different other forms of cancer therapy, including radiation therapy and chemotherapy (Alexander, 2001). The aim of the study was to treat many types of cancer including brain, liver, sarcoma, lung, esophagus, breast, bladder, rectum and peritoneal lining (Kapp et al., 1990, Van der Zee et al., 2000). There are over 100 types of cancers present in the world and are classified according to cell type. According to GLOBOCAN statistics analysis (2012), 14.1 million new cancer cases, 8.2 million cancer deaths and 32.6 million people living with Cancer were reported (Ferlay et al., 2013). The American Cancer society in 2014 provided the annual report, according to which there will be an estimated 1,665,540 new cancer cases diagnosed (ACS). Hyperthermia is under clinical trials (research study with people) and is not widely available. However, while receiving those combination therapies, only few have shown increased survival in patients (Falk and Issels, 2001). Various techniques of hyperthermia are presently under investigation, that include local, regional and whole body hyperthermia (Feldman et al., 2003, Chang et al., 2001). Many of these have shown a significant depression in tumor size when hyperthermia is combined with other treatment or therapy. Attaining temperature above the systemic temperature 37 °C in a specified target volume is a challenge and still under development. High temperature is induced by applying a power density specific absorption rate (SAR; measured in W/kg). Normal basal metabolism of human is above 1 W/kg. Perfusion counteracts the elevated temperature. In humans perfusion rate is around 5–15 ml per 100 g per min, but they differ widely. To reach the elevated temperature approx 42 °C at least in some parts of the body tumors require a power density of approx 20–40 W/kg at the target region (Tilly et al., 2001). (See Table 1, Table 2.) |
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| 18 |
What is a significant potential side effect of whole-body hyperthermia?
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Systemic stress affecting major organs |
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Heating the whole body puts severe thermal stress on the patient, which can overwhelm major systems like the heart and kidneys, similar to a severe heatstroke. |
Whole Body Hyperthermia
Whole body hyperthermia is applied to treat metastatic tumor that has spread throughout the body. A steady state of 42 °C is maintained for 1 h along with the acceptable adverse effects. With the help of sedation of general anesthesia, the procedure would be possible. Application of intubation for the safe administration is still under research. In interaction with the various anesthetics, as compared with local regional methods, an entirely different range of toxic effects arises from the systemic stress (Bull et al., 1982, Kerner et al., 1999). A patient weighing about 70 kg at 37 °C has a basal metabolic rate of 85 W and double that at 42 °C; that in itself was enough to raise the body heat within 180 min between 37·5 °C and 42·0 °C. The power distribution is influenced by three-dimensional anatomy. The transforming network might lead to further limitations in antenna control, as the antenna properties at the feed points were disturbed by coupling and imperfect geometry (Wust et al., 2002). One of the next generations of commercially available applicator was sigma-Eye applicator consisting of three shorter rings, each with four flat dipole-antenna pairs. Magnetic resonance tomography provides treatment monitoring which could characterize temperature as well as perfusion.Side Effects of Regional and Whole-body Hyperthermia
Side effects of regional and whole-body hyperthermia are that it could lead to nausea, vomiting, and diarrhea. In severe cases (rarely) it leads to problems associated with heart, blood vessels, and other major organs. The adverse effects of regional and whole body hyperthermia along with that of other cancer treatments might be possible. But improved technology, experience, and better skills led to fewer side effects. Generally the problems associated with hyperthermia are not serious. |
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| 19 |
Considering the physics of heat transfer, why is controlling hyperthermia challenging during treatment?
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Human tissue has varying thermal conductivities which affect heat distribution. |
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The physics of heat transfer is complex in the body because tissue is heterogeneous (different types/blood flow), making it difficult to achieve uniform heat distribution and maintain the narrow therapeutic temperature range without harming healthy cells. |
Hyperthermia in Association With Radiotherapy
Hyperthermia enhances the oxygenation and perfusion of hypnotic cells, where the ionizing radiation increases three times more than the normal cells. As a result, radiotherapy activity becomes 1.5–5 times more proficient. Hyperthermia has a direct effect on the tumor cells. It acts mostly in the S phase of the cell cycle at an acidic pH, when the cells are radio-resistant. Hence, radiotherapy and hyperthermia are complementary in their action: free radicals are formed from radiotherapy, which thereby damage the DNA of the tumor cells and hyperthermia inhibits its reparation. Radiation damage inhibited by hyperthermia has been an important factor which leads to the synergistic killing effect of the X-rays and hyperthermia. Before the X-irradiation, heating cells have shown to inhibit the DNA strand breaks as well as the excision of base damage (Kampinga and Konings, 1987). Various DNA repair pathways are involved in re-establishment of damage after ionizing irradiation. Heat shock affects the kinetics of all of them. Data reported in 2004 revealed that the thermal inhibition of the non-homologous end-joining pathway plays a role in thermal radio sensitization. However, few data suggested that the homologous recombination pathway may not be the major heat target. Deduction could be the crucial step in the mechanism of radio-sensitization by heat for the inhibition of base-excision (Kampinga et al., 2004). Hyperthermia increases the sensitivity of cells towards radiation and drugs and this sensitization is not directly related to altered heat-shock protein (HSP) expression. Elevating HSP prior to heating makes cells thermo-tolerant and changing their expression will automatically affect the extent of thermal action because the HSP will attenuate the heat-induced protein damage, which is responsible for drug sensitization and radiation. Base-excision damage repair and other hypothermic effects on DNA repair occurred due to nuclear protein damage (Kampinga, 2006).
Hyperthermia in Association With Chemotherapy
Hyperthermia drug sensitization can be found in several anti-cancer drugs, mainly in alkylating agents. Those cells which are already resistant to the drugs, can respond to the same drug with combination therapy (i.e. heat). Hyperthermia, with enhanced tissue perfusion, facilitates the absorption of chemotherapeutic API through cell membrane. In the presence of heat, chemical reaction gets accelerated. Therefore, chemotherapy becomes more effective, and less toxic. A targeted chemotherapy with reduced side effects are provided when, liposomes including adriamycin (Caelyx®) are administered through i.v. Hyperthermia fuses and free its content inside the heated tumor bed. A clinical study of hyperthermia along with radiotherapy was associated from 1989 to 1998. Clinical data allowed obtaining the proof sufficient to establish some recommendations for significant use of hyperthermia (Shrivastava et al., 1989). In Osaka in the year 2004, a clinical group was founded (Kadota Fund International Forum, Kadota, Japan), and its conclusion was published in year 2008 for chemotherapy long with hyperthermia (Emami et al., 1991). The first review was published in 1989 and evaluated the results of non-randomized studies of 24 authors from the USA and Europe on 2234 patients were affected with various types of cancer including — breast cancer, head and neck tumor (Valdagni and Amichetti, 1994). The paper demonstrated that the 36% cancer rate obtained with exclusive radiotherapy was almost doubled with hyperthermia in combination with radiotherapy. Multicentric investigation showed that combination therapy of hyperthermia with radiotherapy improves the results when compared with the radiotherapy or hyperthermia alone |
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| 20 |
Why is hyperthermia considered a beneficial adjunct to radiotherapy and chemotherapy?
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It makes cancer cells more susceptible to other treatments. |
|
It acts as a sensitizer, meaning the heat stresses the cancer cells, making them easier for radiotherapy (by damaging DNA repair) and chemotherapy (by improving drug delivery via increased blood flow) to effectively kill. |
Hyperthermia in Association With Radiotherapy
Hyperthermia enhances the oxygenation and perfusion of hypnotic cells, where the ionizing radiation increases three times more than the normal cells. As a result, radiotherapy activity becomes 1.5–5 times more proficient. Hyperthermia has a direct effect on the tumor cells. It acts mostly in the S phase of the cell cycle at an acidic pH, when the cells are radio-resistant. Hence, radiotherapy and hyperthermia are complementary in their action: free radicals are formed from radiotherapy, which thereby damage the DNA of the tumor cells and hyperthermia inhibits its reparation. Radiation damage inhibited by hyperthermia has been an important factor which leads to the synergistic killing effect of the X-rays and hyperthermia. Before the X-irradiation, heating cells have shown to inhibit the DNA strand breaks as well as the excision of base damage (Kampinga and Konings, 1987). Various DNA repair pathways are involved in re-establishment of damage after ionizing irradiation. Heat shock affects the kinetics of all of them. Data reported in 2004 revealed that the thermal inhibition of the non-homologous end-joining pathway plays a role in thermal radio sensitization. However, few data suggested that the homologous recombination pathway may not be the major heat target. Deduction could be the crucial step in the mechanism of radio-sensitization by heat for the inhibition of base-excision (Kampinga et al., 2004). Hyperthermia increases the sensitivity of cells towards radiation and drugs and this sensitization is not directly related to altered heat-shock protein (HSP) expression. Elevating HSP prior to heating makes cells thermo-tolerant and changing their expression will automatically affect the extent of thermal action because the HSP will attenuate the heat-induced protein damage, which is responsible for drug sensitization and radiation. Base-excision damage repair and other hypothermic effects on DNA repair occurred due to nuclear protein damage (Kampinga, 2006).
Hyperthermia in Association With Chemotherapy
Hyperthermia drug sensitization can be found in several anti-cancer drugs, mainly in alkylating agents. Those cells which are already resistant to the drugs, can respond to the same drug with combination therapy (i.e. heat). Hyperthermia, with enhanced tissue perfusion, facilitates the absorption of chemotherapeutic API through cell membrane. In the presence of heat, chemical reaction gets accelerated. Therefore, chemotherapy becomes more effective, and less toxic. A targeted chemotherapy with reduced side effects are provided when, liposomes including adriamycin (Caelyx®) are administered through i.v. Hyperthermia fuses and free its content inside the heated tumor bed. A clinical study of hyperthermia along with radiotherapy was associated from 1989 to 1998. Clinical data allowed obtaining the proof sufficient to establish some recommendations for significant use of hyperthermia (Shrivastava et al., 1989). In Osaka in the year 2004, a clinical group was founded (Kadota Fund International Forum, Kadota, Japan), and its conclusion was published in year 2008 for chemotherapy long with hyperthermia (Emami et al., 1991). The first review was published in 1989 and evaluated the results of non-randomized studies of 24 authors from the USA and Europe on 2234 patients were affected with various types of cancer including — breast cancer, head and neck tumor (Valdagni and Amichetti, 1994). The paper demonstrated that the 36% cancer rate obtained with exclusive radiotherapy was almost doubled with hyperthermia in combination with radiotherapy. Multicentric investigation showed that combination therapy of hyperthermia with radiotherapy improves the results when compared with the radiotherapy or hyperthermia alone. |
7 |
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|