Transcranial low-level laser (light) therapy (LLLT) is a new non-invasive approach to treating a ... more Transcranial low-level laser (light) therapy (LLLT) is a new non-invasive approach to treating a range of brain disorders including traumatic brain injury (TBI). We (and others) have shown that applying near-infrared light to the head of animals that have suffered TBI produces improvement in neurological functioning, lessens the size of the brain lesion, reduces neuroinflammation, and stimulates the formation of new neurons. In the present study we used a controlled cortical impact TBI in mice and treated the mice either once (4 h post-TBI, 1-laser), or three daily applications (3-laser) with 810 nm CW laser 36 J/cm(2) at 50 mW/cm(2) . Similar to previous studies, the neurological severity score improved in laser-treated mice compared to untreated TBI mice at day 14 and continued to further improve at days 21 and 28 with 3-laser being better than 1-laser. Mice were sacrificed at days 7 and 28 and brains removed for immunofluorescence analysis. Brain-derived neurotrophic factor (BDNF...
Photodynamic therapy (PDT) employs the combination of nontoxic photosensitizers and visible light... more Photodynamic therapy (PDT) employs the combination of nontoxic photosensitizers and visible light that is absorbed by the chromophore to produce long-lived triplet states that can carry out photochemistry in the presence of oxygen to kill cells. The closed carbon-cage structure found in fullerenes can act as a photosensitizer, especially when functionalized to impart water solubility. Although there are reports of the use of fullerenes to carry out light-mediated destruction of viruses, microorganisms and cancer cells in vitro, the use of fullerenes to mediate PDT of diseases such as cancer and infections in animal models is less well developed. It has recently been shown that fullerene PDT can be used to save the life of mice with wounds infected with pathogenic Gram-negative bacteria. Fullerene PDT has also been used to treat mouse models of various cancers including disseminated metastatic cancer in the peritoneal cavity. In vivo PDT with fullerenes represents a new application in nanomedicine.
The Journal of Horticultural Science and Biotechnology, 2000
Genetic resources of the medicinal and vegetable plant C. asiatica, collected from different part... more Genetic resources of the medicinal and vegetable plant C. asiatica, collected from different parts of India, were screened for their herb and asiaticoside yields under different levels of shading, under subtropical field conditions of Indo-Gangetic plains at Lucknow, Uttar ...
We investigated tumor regression and the mode of tumor cell death induced by photodynamic treatme... more We investigated tumor regression and the mode of tumor cell death induced by photodynamic treatment (PDT) with chlorin p(6) (Cp(6)) in hamster cheek pouch model of oral squamous cell carcinoma. Cp(6) was administered systemically through intraperitoneal injection and after 4h the tumors were subjected to photodynamic treatment using red light (660±25nm, fluence ∼100J/cm(2)). Tumor response to PDT was monitored by measuring the tumor volume before PDT and 1week after. Results show that smaller tumors (⩽80mm(3)) regressed completely after PDT with Cp(6) dose of 2.0mg/kg body weight and for the bigger tumors (∼180mm(3)) higher dose of Cp(6) (4.0mg/kg) was more effective. Tumors treated with lower Cp(6) dose showed infiltration of immune cells, absence of TUNEL labeling, smeared pattern of DNA fragmentation and no significant increase in caspase-3 activity suggestive of necrotic cell death and inflammation. In tumors treated with higher Cp(6) dose, features characteristic of apoptotic cell death such as extensive TUNEL positive labeling, increase in caspase-3 activity and laddered pattern of DNA fragmentation were observed and there was no infiltration of immune cells. PDT with Cp(6) was also found to lead to expression of matrix metalloprotease-9 (MMP-9) which was greater at lower drug dose PDT as compared to higher drug dose PDT. These results suggest that drug dose plays an important role in determining the mechanism of tumor cell death and effectiveness of PDT.
Melanoma is a dreaded form of skin cancer caused by the malignant transformation of skin melanocy... more Melanoma is a dreaded form of skin cancer caused by the malignant transformation of skin melanocytes and can be highly aggressive and has a rapidly growing incidence and elevated mortality and a poor prognosis at an advanced stage. Because melanomas are intrinsically resistant to conventional radiotherapy and chemotherapy, many alternative treatment approaches are being developed. Photodynamic therapy (PDT) has shown promising results for the treatment of different types of cancer. This therapy involves administration of a photosensitizer (PS), which on excitation after suitable irradiation generates singlet oxygen and other cytotoxic reactive oxygen species (ROS), thus, killing the cancer cells. Unfortunately, melanoma is considered to be resistant to PDT. There are many different reasons for this resistance including: (1) optical interference by melanin; (2) the anti-oxidant effect of melanin (3) sequestration of PS inside melanosomes (4) efflux of PS by multi-drug transporters an...
Photodynamic inactivation of pathogenic bacteria and cancer cells by novel water-soluble decacati... more Photodynamic inactivation of pathogenic bacteria and cancer cells by novel water-soluble decacationic fullerene monoadducts, C60[>M(C3N6 (+)C3)2] and C70[>M(C3N6 (+)C3)2], were investigated. In the presence of a high number of electron-donating iodide anions as parts of quaternary ammonium salts in the arm region, we found that C70[>M(C3N6 (+)C3)2] produced more highly reactive HO(•) radical than C60[>M(C3N6 (+)C3)2], in addition to singlet oxygen ((1)O2). This finding offers an explanation of the preferential killing of Gram-positive and Gram-negative bacteria by C60[>M(C3N6 (+)C3)2] and C70[>M(C3N6 (+)C3)2], respectively. The hypothesis is that (1)O2 can diffuse more easily into porous cell walls of Gram-positive bacteria to reach sensitive sites, while the less permeable Gram-negative bacterial cell wall needs the more reactive HO(•) to cause real damage.
Since the discovery of C 60 fullerene in 1985, scientists have been searching for biomedical appl... more Since the discovery of C 60 fullerene in 1985, scientists have been searching for biomedical applications of this most fascinating of molecules. The unique photophysical and photochemical properties of C 60 suggested that the molecule would function well as a photosensitizer in photodynamic therapy (PDT). PDT uses the combination of non-toxic dyes and harmless visible light to produce reactive oxygen species that kill unwanted cells. However the extreme insolubility and hydrophobicity of pristine C 60 , mandated that the cage be functionalized with chemical groups that provided water solubility and biological targeting ability. It has been found that cationic quaternary ammonium groups provide both these features, and this review covers work on the use of cationic fullerenes to mediate destruction of cancer cells and pathogenic microorganisms in vitro and describes the treatment of tumors and microbial infections in mouse models. The design, synthesis, and use of simple pyrrolidinium salts, more complex decacationic chains, and light-harvesting antennae that can be attached to C 60 , C 70 and C 84 cages are covered. In the case of bacterial wound infections mice can be saved from certain death by fullerene-mediated PDT.
Background and Objective-Photodynamic therapy (PDT) was discovered over 100 years ago by its abil... more Background and Objective-Photodynamic therapy (PDT) was discovered over 100 years ago by its ability to kill various microorganisms when the appropriate dye and light were combined in the presence of oxygen. However it is only in relatively recent times that PDT has been studied as a treatment for various types of localized infections. This resurgence of interest has been partly motivated by the alarming increase in drug resistance amongst bacteria and other pathogens. This review will focus on the clinical applications of antimicrobial PDT.
ᮀ Low-level laser (light) therapy (LLLT) has been known since 1967 but still remains controversia... more ᮀ Low-level laser (light) therapy (LLLT) has been known since 1967 but still remains controversial due to incomplete understanding of the basic mechanisms and the selection of inappropriate dosimetric parameters that led to negative studies. The biphasic doseresponse or Arndt-Schulz curve in LLLT has been shown both in vitro studies and in animal experiments. This review will provide an update to our previous coverage of this topic. In vitro mediators of LLLT such as adenosine triphosphate (ATP) and mitochondrial membrane potential show biphasic patterns, while others such as mitochondrial reactive oxygen species show a triphasic dose-response with two distinct peaks. The Janus nature of reactive oxygen species (ROS) that may act as a beneficial signaling molecule at low concentrations and a harmful cytotoxic agent at high concentrations, may partly explain the observed responses in vivo. Transcranial LLLT for traumatic brain injury (TBI) in mice shows a distinct biphasic pattern with peaks in beneficial neurological effects observed when the number of treatments is varied, and when the energy density of an individual treatment is varied. Further understanding of the extent to which biphasic dose responses apply in LLLT will be necessary to optimize clinical treatments.
Transcranial low-level laser therapy (LLLT) using near-infrared light can efficiently penetrate t... more Transcranial low-level laser therapy (LLLT) using near-infrared light can efficiently penetrate through the scalp and skull and could allow non-invasive treatment for traumatic brain injury (TBI). In the present study, we compared the therapeutic effect using 810-nm wavelength laser light in continuous and pulsed wave modes in a mouse model of TBI. TBI was induced by a controlled cortical-impact device and 4-hours post-TBI 1-group received a sham treatment and 3-groups received a single exposure to transcranial LLLT, either continuous wave or pulsed at 10-Hz or 100-Hz with a 50% duty cycle. An 810-nm Ga-Al-As diode laser delivered a spot with diameter of 1-cm onto the injured head with a power density of 50-mW/cm(2) for 12-minutes giving a fluence of 36-J/cm(2). Neurological severity score (NSS) and body weight were measured up to 4 weeks. Mice were sacrificed at 2, 15 and 28 days post-TBI and the lesion size was histologically analyzed. The quantity of ATP production in the brain t...
There are many reports showing that low-level light/laser therapy (LLLT) can enhance wound healin... more There are many reports showing that low-level light/laser therapy (LLLT) can enhance wound healing, upregulate cell proliferation and has anti-apoptotic effects by activating intracellular protective genes. In the field of immune response study, it is not known with any certainty whether light/laser is proinflammatory or anti-inflammatory. Increasingly in recent times dendritic cells have been found to play an important role in inflammation and the immunological response. In this study, we try to look at the impact of low level near infrared light (810-nm) on murine bone-marrow derived dendritic cells. Changes in surface markers, including MHC II, CD80 and CD11c and the secretion of interleukins induced by light may provide additional evidence to reveal the mystery of how light affects the maturation of dendritic cells as well how these light-induced mature dendritic cells would affect the activation of adaptive immune response.
Biological warfare and bioterrorism is an unpleasant fact of 21st century life. Highly infectious... more Biological warfare and bioterrorism is an unpleasant fact of 21st century life. Highly infectious and profoundly virulent diseases may be caused in combat personnel or in civilian populations by the appropriate dissemination of viruses, bacteria, spores, fungi, or toxins. Dissemination may be airborne, waterborne, or by contamination of food or surfaces. Countermeasures may be directed toward destroying or neutralizing the agents outside the body before infection has taken place, by destroying the agents once they have entered the body before the disease has fully developed, or by immunizing susceptible populations against the effects. A range of light-based technologies may have a role to play in biodefense countermeasures. Germicidal UV (UVC) is exceptionally active in destroying a wide range of viruses and microbial cells, and recent data suggests that UVC has high selectivity over host mammalian cells and tissues. Two UVA mediated approaches may also have roles to play; one wher...
Transcranial low-level laser (light) therapy (LLLT) is a new non-invasive approach to treating a ... more Transcranial low-level laser (light) therapy (LLLT) is a new non-invasive approach to treating a range of brain disorders including traumatic brain injury (TBI). We (and others) have shown that applying near-infrared light to the head of animals that have suffered TBI produces improvement in neurological functioning, lessens the size of the brain lesion, reduces neuroinflammation, and stimulates the formation of new neurons. In the present study we used a controlled cortical impact TBI in mice and treated the mice either once (4 h post-TBI, 1-laser), or three daily applications (3-laser) with 810 nm CW laser 36 J/cm(2) at 50 mW/cm(2) . Similar to previous studies, the neurological severity score improved in laser-treated mice compared to untreated TBI mice at day 14 and continued to further improve at days 21 and 28 with 3-laser being better than 1-laser. Mice were sacrificed at days 7 and 28 and brains removed for immunofluorescence analysis. Brain-derived neurotrophic factor (BDNF...
Photodynamic therapy (PDT) employs the combination of nontoxic photosensitizers and visible light... more Photodynamic therapy (PDT) employs the combination of nontoxic photosensitizers and visible light that is absorbed by the chromophore to produce long-lived triplet states that can carry out photochemistry in the presence of oxygen to kill cells. The closed carbon-cage structure found in fullerenes can act as a photosensitizer, especially when functionalized to impart water solubility. Although there are reports of the use of fullerenes to carry out light-mediated destruction of viruses, microorganisms and cancer cells in vitro, the use of fullerenes to mediate PDT of diseases such as cancer and infections in animal models is less well developed. It has recently been shown that fullerene PDT can be used to save the life of mice with wounds infected with pathogenic Gram-negative bacteria. Fullerene PDT has also been used to treat mouse models of various cancers including disseminated metastatic cancer in the peritoneal cavity. In vivo PDT with fullerenes represents a new application in nanomedicine.
The Journal of Horticultural Science and Biotechnology, 2000
Genetic resources of the medicinal and vegetable plant C. asiatica, collected from different part... more Genetic resources of the medicinal and vegetable plant C. asiatica, collected from different parts of India, were screened for their herb and asiaticoside yields under different levels of shading, under subtropical field conditions of Indo-Gangetic plains at Lucknow, Uttar ...
We investigated tumor regression and the mode of tumor cell death induced by photodynamic treatme... more We investigated tumor regression and the mode of tumor cell death induced by photodynamic treatment (PDT) with chlorin p(6) (Cp(6)) in hamster cheek pouch model of oral squamous cell carcinoma. Cp(6) was administered systemically through intraperitoneal injection and after 4h the tumors were subjected to photodynamic treatment using red light (660±25nm, fluence ∼100J/cm(2)). Tumor response to PDT was monitored by measuring the tumor volume before PDT and 1week after. Results show that smaller tumors (⩽80mm(3)) regressed completely after PDT with Cp(6) dose of 2.0mg/kg body weight and for the bigger tumors (∼180mm(3)) higher dose of Cp(6) (4.0mg/kg) was more effective. Tumors treated with lower Cp(6) dose showed infiltration of immune cells, absence of TUNEL labeling, smeared pattern of DNA fragmentation and no significant increase in caspase-3 activity suggestive of necrotic cell death and inflammation. In tumors treated with higher Cp(6) dose, features characteristic of apoptotic cell death such as extensive TUNEL positive labeling, increase in caspase-3 activity and laddered pattern of DNA fragmentation were observed and there was no infiltration of immune cells. PDT with Cp(6) was also found to lead to expression of matrix metalloprotease-9 (MMP-9) which was greater at lower drug dose PDT as compared to higher drug dose PDT. These results suggest that drug dose plays an important role in determining the mechanism of tumor cell death and effectiveness of PDT.
Melanoma is a dreaded form of skin cancer caused by the malignant transformation of skin melanocy... more Melanoma is a dreaded form of skin cancer caused by the malignant transformation of skin melanocytes and can be highly aggressive and has a rapidly growing incidence and elevated mortality and a poor prognosis at an advanced stage. Because melanomas are intrinsically resistant to conventional radiotherapy and chemotherapy, many alternative treatment approaches are being developed. Photodynamic therapy (PDT) has shown promising results for the treatment of different types of cancer. This therapy involves administration of a photosensitizer (PS), which on excitation after suitable irradiation generates singlet oxygen and other cytotoxic reactive oxygen species (ROS), thus, killing the cancer cells. Unfortunately, melanoma is considered to be resistant to PDT. There are many different reasons for this resistance including: (1) optical interference by melanin; (2) the anti-oxidant effect of melanin (3) sequestration of PS inside melanosomes (4) efflux of PS by multi-drug transporters an...
Photodynamic inactivation of pathogenic bacteria and cancer cells by novel water-soluble decacati... more Photodynamic inactivation of pathogenic bacteria and cancer cells by novel water-soluble decacationic fullerene monoadducts, C60[>M(C3N6 (+)C3)2] and C70[>M(C3N6 (+)C3)2], were investigated. In the presence of a high number of electron-donating iodide anions as parts of quaternary ammonium salts in the arm region, we found that C70[>M(C3N6 (+)C3)2] produced more highly reactive HO(•) radical than C60[>M(C3N6 (+)C3)2], in addition to singlet oxygen ((1)O2). This finding offers an explanation of the preferential killing of Gram-positive and Gram-negative bacteria by C60[>M(C3N6 (+)C3)2] and C70[>M(C3N6 (+)C3)2], respectively. The hypothesis is that (1)O2 can diffuse more easily into porous cell walls of Gram-positive bacteria to reach sensitive sites, while the less permeable Gram-negative bacterial cell wall needs the more reactive HO(•) to cause real damage.
Since the discovery of C 60 fullerene in 1985, scientists have been searching for biomedical appl... more Since the discovery of C 60 fullerene in 1985, scientists have been searching for biomedical applications of this most fascinating of molecules. The unique photophysical and photochemical properties of C 60 suggested that the molecule would function well as a photosensitizer in photodynamic therapy (PDT). PDT uses the combination of non-toxic dyes and harmless visible light to produce reactive oxygen species that kill unwanted cells. However the extreme insolubility and hydrophobicity of pristine C 60 , mandated that the cage be functionalized with chemical groups that provided water solubility and biological targeting ability. It has been found that cationic quaternary ammonium groups provide both these features, and this review covers work on the use of cationic fullerenes to mediate destruction of cancer cells and pathogenic microorganisms in vitro and describes the treatment of tumors and microbial infections in mouse models. The design, synthesis, and use of simple pyrrolidinium salts, more complex decacationic chains, and light-harvesting antennae that can be attached to C 60 , C 70 and C 84 cages are covered. In the case of bacterial wound infections mice can be saved from certain death by fullerene-mediated PDT.
Background and Objective-Photodynamic therapy (PDT) was discovered over 100 years ago by its abil... more Background and Objective-Photodynamic therapy (PDT) was discovered over 100 years ago by its ability to kill various microorganisms when the appropriate dye and light were combined in the presence of oxygen. However it is only in relatively recent times that PDT has been studied as a treatment for various types of localized infections. This resurgence of interest has been partly motivated by the alarming increase in drug resistance amongst bacteria and other pathogens. This review will focus on the clinical applications of antimicrobial PDT.
ᮀ Low-level laser (light) therapy (LLLT) has been known since 1967 but still remains controversia... more ᮀ Low-level laser (light) therapy (LLLT) has been known since 1967 but still remains controversial due to incomplete understanding of the basic mechanisms and the selection of inappropriate dosimetric parameters that led to negative studies. The biphasic doseresponse or Arndt-Schulz curve in LLLT has been shown both in vitro studies and in animal experiments. This review will provide an update to our previous coverage of this topic. In vitro mediators of LLLT such as adenosine triphosphate (ATP) and mitochondrial membrane potential show biphasic patterns, while others such as mitochondrial reactive oxygen species show a triphasic dose-response with two distinct peaks. The Janus nature of reactive oxygen species (ROS) that may act as a beneficial signaling molecule at low concentrations and a harmful cytotoxic agent at high concentrations, may partly explain the observed responses in vivo. Transcranial LLLT for traumatic brain injury (TBI) in mice shows a distinct biphasic pattern with peaks in beneficial neurological effects observed when the number of treatments is varied, and when the energy density of an individual treatment is varied. Further understanding of the extent to which biphasic dose responses apply in LLLT will be necessary to optimize clinical treatments.
Transcranial low-level laser therapy (LLLT) using near-infrared light can efficiently penetrate t... more Transcranial low-level laser therapy (LLLT) using near-infrared light can efficiently penetrate through the scalp and skull and could allow non-invasive treatment for traumatic brain injury (TBI). In the present study, we compared the therapeutic effect using 810-nm wavelength laser light in continuous and pulsed wave modes in a mouse model of TBI. TBI was induced by a controlled cortical-impact device and 4-hours post-TBI 1-group received a sham treatment and 3-groups received a single exposure to transcranial LLLT, either continuous wave or pulsed at 10-Hz or 100-Hz with a 50% duty cycle. An 810-nm Ga-Al-As diode laser delivered a spot with diameter of 1-cm onto the injured head with a power density of 50-mW/cm(2) for 12-minutes giving a fluence of 36-J/cm(2). Neurological severity score (NSS) and body weight were measured up to 4 weeks. Mice were sacrificed at 2, 15 and 28 days post-TBI and the lesion size was histologically analyzed. The quantity of ATP production in the brain t...
There are many reports showing that low-level light/laser therapy (LLLT) can enhance wound healin... more There are many reports showing that low-level light/laser therapy (LLLT) can enhance wound healing, upregulate cell proliferation and has anti-apoptotic effects by activating intracellular protective genes. In the field of immune response study, it is not known with any certainty whether light/laser is proinflammatory or anti-inflammatory. Increasingly in recent times dendritic cells have been found to play an important role in inflammation and the immunological response. In this study, we try to look at the impact of low level near infrared light (810-nm) on murine bone-marrow derived dendritic cells. Changes in surface markers, including MHC II, CD80 and CD11c and the secretion of interleukins induced by light may provide additional evidence to reveal the mystery of how light affects the maturation of dendritic cells as well how these light-induced mature dendritic cells would affect the activation of adaptive immune response.
Biological warfare and bioterrorism is an unpleasant fact of 21st century life. Highly infectious... more Biological warfare and bioterrorism is an unpleasant fact of 21st century life. Highly infectious and profoundly virulent diseases may be caused in combat personnel or in civilian populations by the appropriate dissemination of viruses, bacteria, spores, fungi, or toxins. Dissemination may be airborne, waterborne, or by contamination of food or surfaces. Countermeasures may be directed toward destroying or neutralizing the agents outside the body before infection has taken place, by destroying the agents once they have entered the body before the disease has fully developed, or by immunizing susceptible populations against the effects. A range of light-based technologies may have a role to play in biodefense countermeasures. Germicidal UV (UVC) is exceptionally active in destroying a wide range of viruses and microbial cells, and recent data suggests that UVC has high selectivity over host mammalian cells and tissues. Two UVA mediated approaches may also have roles to play; one wher...
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