Grounding or earthing involves making physical contact with the Earth's surface by walking barefoot on natural surfaces or using grounding devices that simulate direct contact with the Earth.Precision Grounding is...Grounding or earthing involves making physical contact with the Earth's surface by walking barefoot on natural surfaces or using grounding devices that simulate direct contact with the Earth.Precision Grounding is believed to balance the electrical charge in the human body and has potential physical and psychological benefits,including reduced inflammation,improved sleep quality,and decreased anxiety and depression symptoms.Combining earthing therapy with essential oils is gaining popularity as a natural and effective therapeutic technique.Essential oils contain antioxidants and anti-inflammatory chemicals that complement the benefits of earthing therapy.This study aims to highlight a novel method for reducing inflammation by combining essential oils with precision grounding and to emphasize the significance of the duration and intensity of grounding on inflammation and injury.The findings indicate that essential oils combined with precision grounding can reduce pain and alter the levels of neutrophils,lymphocytes,and inflammation-related chemicals in circulation.The review underscores the potential of earthing with essential oils as a simple and widely available clinical intervention with potentially significant therapeutic implications.Precision Grounding therapy is safe and theoretically beneficial for most people,but medical advice should be sought before beginning any new wellness practice.展开更多
Peripheral vision loss followed by "tunnel vision" and eventual irreversible blindness is the fate of patients afflicted by various forms of glaucoma including primary open-angle glaucoma(POAG) and normotensive gl...Peripheral vision loss followed by "tunnel vision" and eventual irreversible blindness is the fate of patients afflicted by various forms of glaucoma including primary open-angle glaucoma(POAG) and normotensive glaucoma(NTG).These complex and heterogeneous diseases are characterized by extensive death of retinal ganglion cells(RGCs) accompanied by retraction and severance of their axonal connections to the brain and thus damage to and thinning of the optic nerve.Since patients suffering from this glaucomatous optic neuropathy(GON) first notice visual impairment when they have lost 〉 40% of their RGCs,early diagnosis is the key to retard the progression of glaucoma.Elevated intraocular pressure(IOP),low cerebrospinal and/or low intracranial fluid pressure,advancing age,and ethnicity are major risk factors associated with POAG.However,retinal vascular abnormalities and a high sensitivity of RGCs and optic nerve head components to neurotoxic,inflammatory,oxidative and mechanical insults also contribute to vision loss in POAG/GON.Current treatment modalities for POAG and NTG involve lowering IOP using topical ocular drugs,combination drug products,and surgical interventions.Two recently approved multi-pharmacophoric drugs(e.g.,rho kinase inhibitor,Netarsudil;a drug conjugate,Latanoprostene Bunod) and novel aqueous humor drainage devices(i Stent and Cy Pass) are also gaining acceptance for treating POAG/NTG.Neuroprotective and regenerative agents,coupled with electroceutical,mechanical support systems,stem cell transplantation and gene therapy are emerging therapeutics on the horizon to help combat GON.The latter techniques and approaches hope to rejuvenate RGCs and repair the optic nerve structures,thereby providing a gain of function of the visual system for the glaucoma patients.展开更多
OBJECTIVE To elucidate the structural-pharmacokinetic relationship and identify resveratrol analogs with favorable pharmacokinetic profiles for potential medicinal application. METHODS The pharmacokinetic data of resv...OBJECTIVE To elucidate the structural-pharmacokinetic relationship and identify resveratrol analogs with favorable pharmacokinetic profiles for potential medicinal application. METHODS The pharmacokinetic data of resveratrol(trans-3,5,4-trihydroxystilbene),pterostilbene(trans-3,5-dimethoxy-4-hydroxystilbene),resveratrol trimethyl ether(trans-3,5,4-trimethoxystilbene)and some other herbal resveratrol analogs were extracted from the authors′recent publications and compared.RESULTS Aqueous solubility,to different extent,has been identified as a barrier to oral absorption of resveratrol and its analogs.In addition,the para hydroxyl group(s)on the aromatic ring was less liable to metabolism compared to the meta-hydroxyl group(s).Pterostilbene and resveratrol trimethyl ether displayed more superior pharmacokinetic properties than resveratrol,i.e.much slower clearance and abundant plasma exposure.CONCLUSION Pterostilbene appears to be a favorable candidate for further development.Resveratrol analogs with meta-hydroxyl group(s)might have poor metabolic stability and suffer from rapid clearance and low oral bioavailability.展开更多
During the clinical course of dementia,beside cognitive impairment and memory loss,a very complex challenge is posed by the neuropsychiatric symptoms(NPSs).Accurate evaluation and treatment of pain impacts positivel...During the clinical course of dementia,beside cognitive impairment and memory loss,a very complex challenge is posed by the neuropsychiatric symptoms(NPSs).Accurate evaluation and treatment of pain impacts positively the agitation of demented patients aged ≥ 65 years.To gather information on the utilization of pain killers in demented patients a preliminary survey has been conducted in collaboration with the Calabrian Pharmacovigilance Territorial Service of the health district of Catanzaro(Italy).The study has taken into consideration the prescriptions of acetylcholinesterase inhibitors and memantine during the period ranging from July 2015 to June 2016 and the percentage of patients treated against pain with non steroidal antinflammatory drugs,opioids,and anticonvulsants have been monitored.The latter have been evaluated statistically for difference between the treatment before(pre) and after(post) the settlement of acetylcholinesterase inhibitors(ACh EI) or memantine therapy.The results do support accuracy in painkillers utilization in the course of dementia in the regional population of Calabria(Italy).展开更多
The high morbidity generated by the infection caused by parasites of the genus Leishmania, make of this infection into one of the vector-borne infectious diseases most relevant worldwide, which added to the fact that ...The high morbidity generated by the infection caused by parasites of the genus Leishmania, make of this infection into one of the vector-borne infectious diseases most relevant worldwide, which added to the fact that the drugs used for its treatment are far from be optimal and considering that prophylactic approaches (such as the development of a vaccine) still seems far from being achieved, make of the search for new therapeutic alternatives for safe and effective treatment of this disease one of the most accurate approaches to the control of this disease. In this study we evaluated the antileishmanial and immunomodu- latory activity of the compound 11α,19β-dihydroxy- 7-acetoxy-7-deoxoichangin (a seco-limonid molecule) through: 1) evaluation of its cytotoxicity over promastigotes and axenic amastigotes of L. (V) panamensis, 2) determination of its ability to induce the control of in vitro infection, using infected murine cells (J774.2) and human dendritic cells (hDCs), 3) quantifying the levels of pro-inflammatory cytokines, (iv) evaluating the expression of cell markers associated with hDCs maturation, and (v) determinating the production of nitric oxide free radicals (NO). In this regard, this seco-limonoid exhibited an antileishmanial activity represented in the reduction of in vitro infection in J774.2 cells and hDCs, with a EC50 of 7.9 μM (4.48 μg/mL) and 25.5 μM (14.39 μg/mL), respectively, and additionally, we observed an increase on the production of IL-12p70, TNF-α and NO, as also, in the number of hDCs HLA-DR-positive in treated infected hDCs. These findings suggest that anti-lei- shmanial activity of this compound could be associated with the potential “reactivation” of phagocytic cell that is “paralyzed” by the infection, generating an immune phenotype associated with protection.展开更多
Cellular and mitochondrial membrane phospholipids provide the substrate for synthesis and release of prostaglandins in response to certain chemical,mechanical,noxious and other stimuli.Prostaglandin D_(2),prostaglandi...Cellular and mitochondrial membrane phospholipids provide the substrate for synthesis and release of prostaglandins in response to certain chemical,mechanical,noxious and other stimuli.Prostaglandin D_(2),prostaglandin E_(2),prostaglandin F_(2)α,prostaglandin I_(2)and thromboxane-A_(2)interact with five major receptors(and their sub-types)to elicit specific downstream cellular and tissue actions.In general,prostaglandins have been associated with pain,inflammation,and edema when they are present at high local concentrations and involved on a chronic basis.However,in acute settings,certain endogenous and exogenous prostaglandins have beneficial effects ranging from mediating muscle contraction/relaxation,providing cellular protection,regulating sleep,and enhancing blood flow,to lowering intraocular pressure to prevent the development of glaucoma,a blinding disease.Several classes of prostaglandins are implicated(or are considered beneficial)in certain central nervous system dysfunctions(e.g.,Alzheimer’s,Parkinson’s,and Huntington’s diseases;amyotrophic lateral sclerosis and multiple sclerosis;stroke,traumatic brain injuries and pain)and in ocular disorders(e.g.,ocular hypertension and glaucoma;allergy and inflammation;edematous retinal disorders).This review endeavors to address the physiological/pathological roles of prostaglandins in the central nervous system and ocular function in health and disease,and provides insights towards the therapeutic utility of some prostaglandin agonists and antagonists,polyunsaturated fatty acids,and cyclooxygenase inhibitors.展开更多
Background: Vein graft failure after bypass surgery is greatly increase in patients with diabetes mellitus. The cellular mechanisms underlying the cause of this failure are largely unexplored. Protein kinase B/AKT is ...Background: Vein graft failure after bypass surgery is greatly increase in patients with diabetes mellitus. The cellular mechanisms underlying the cause of this failure are largely unexplored. Protein kinase B/AKT is a mechanically sensitive regulator of cellular growth and apoptosis. Herein we examine whether diabetes affects the regulation of AKT in response to increased venous loading. Methods: Inferior venae cavae (IVC) from the non-diabetic lean (LNZ) and the diabetic obese?syndrome X Zucker(OSXZ) rats were isolated and incubated ex vivo under basal or pressurized conditions (120 mmHg). Protein expression, basal activation and the ability of increased pressure to activate AKT3 and apoptosis-related signaling were evaluated by immunoblot analysis. Results: Compared to that seen in the non-diabetic lean animals, increased venous pressure in the OSXZ rats was not characterized by increases in APAF-1 concentration, XIAP proteolysis, AIF cleavage, or Bad phosphorylation. This evidence of decreased apoptotic signaling was associated with increased basal p-AKT3 levels (+136% ± 13% P < 0.05 higher in the OSXZ vs. LNZ IVC). Conclusion: These data suggest that diabetes-associated increases in p-AKT3 may alter the ability of the IVC to undergo pressure induced apoptosis-related signaling. Further investigation is required to determine whether these changes are associated with the increased vein graft attrition seen in the diabetic population.展开更多
Natural products or natural product derived drugs comprised 32% of small molecule approved drugs between 1981 and 2010.In the same period of time,16% of small molecule approved drugs were synthetic or natural mimics b...Natural products or natural product derived drugs comprised 32% of small molecule approved drugs between 1981 and 2010.In the same period of time,16% of small molecule approved drugs were synthetic or natural mimics based on the study of pharmacophores related to natural products.Indisputably,natural products provide diverse structural diversity and intricate carboskeletal frameworks.As it is believed that nature has evolved optimized biologically active compounds-the secondary metabolites-to ensure survival of the species that produce them,natural products are perceived by some to be more′drug-like′than totally synthetic compounds.As such,natural products may provide us with the′best′lead compounds yet for drug discovery,giving rise to natural product inspired drug design.This talk will provide an overview of some of my research in this area.Specifically,I will outline the challenges and some of the lessons learnt in this quest to develop natural products as leads to potential drugs.展开更多
文摘Grounding or earthing involves making physical contact with the Earth's surface by walking barefoot on natural surfaces or using grounding devices that simulate direct contact with the Earth.Precision Grounding is believed to balance the electrical charge in the human body and has potential physical and psychological benefits,including reduced inflammation,improved sleep quality,and decreased anxiety and depression symptoms.Combining earthing therapy with essential oils is gaining popularity as a natural and effective therapeutic technique.Essential oils contain antioxidants and anti-inflammatory chemicals that complement the benefits of earthing therapy.This study aims to highlight a novel method for reducing inflammation by combining essential oils with precision grounding and to emphasize the significance of the duration and intensity of grounding on inflammation and injury.The findings indicate that essential oils combined with precision grounding can reduce pain and alter the levels of neutrophils,lymphocytes,and inflammation-related chemicals in circulation.The review underscores the potential of earthing with essential oils as a simple and widely available clinical intervention with potentially significant therapeutic implications.Precision Grounding therapy is safe and theoretically beneficial for most people,but medical advice should be sought before beginning any new wellness practice.
文摘Peripheral vision loss followed by "tunnel vision" and eventual irreversible blindness is the fate of patients afflicted by various forms of glaucoma including primary open-angle glaucoma(POAG) and normotensive glaucoma(NTG).These complex and heterogeneous diseases are characterized by extensive death of retinal ganglion cells(RGCs) accompanied by retraction and severance of their axonal connections to the brain and thus damage to and thinning of the optic nerve.Since patients suffering from this glaucomatous optic neuropathy(GON) first notice visual impairment when they have lost 〉 40% of their RGCs,early diagnosis is the key to retard the progression of glaucoma.Elevated intraocular pressure(IOP),low cerebrospinal and/or low intracranial fluid pressure,advancing age,and ethnicity are major risk factors associated with POAG.However,retinal vascular abnormalities and a high sensitivity of RGCs and optic nerve head components to neurotoxic,inflammatory,oxidative and mechanical insults also contribute to vision loss in POAG/GON.Current treatment modalities for POAG and NTG involve lowering IOP using topical ocular drugs,combination drug products,and surgical interventions.Two recently approved multi-pharmacophoric drugs(e.g.,rho kinase inhibitor,Netarsudil;a drug conjugate,Latanoprostene Bunod) and novel aqueous humor drainage devices(i Stent and Cy Pass) are also gaining acceptance for treating POAG/NTG.Neuroprotective and regenerative agents,coupled with electroceutical,mechanical support systems,stem cell transplantation and gene therapy are emerging therapeutics on the horizon to help combat GON.The latter techniques and approaches hope to rejuvenate RGCs and repair the optic nerve structures,thereby providing a gain of function of the visual system for the glaucoma patients.
基金The project supported by a start-up grant from the National University of Singapore(R148000174133)
文摘OBJECTIVE To elucidate the structural-pharmacokinetic relationship and identify resveratrol analogs with favorable pharmacokinetic profiles for potential medicinal application. METHODS The pharmacokinetic data of resveratrol(trans-3,5,4-trihydroxystilbene),pterostilbene(trans-3,5-dimethoxy-4-hydroxystilbene),resveratrol trimethyl ether(trans-3,5,4-trimethoxystilbene)and some other herbal resveratrol analogs were extracted from the authors′recent publications and compared.RESULTS Aqueous solubility,to different extent,has been identified as a barrier to oral absorption of resveratrol and its analogs.In addition,the para hydroxyl group(s)on the aromatic ring was less liable to metabolism compared to the meta-hydroxyl group(s).Pterostilbene and resveratrol trimethyl ether displayed more superior pharmacokinetic properties than resveratrol,i.e.much slower clearance and abundant plasma exposure.CONCLUSION Pterostilbene appears to be a favorable candidate for further development.Resveratrol analogs with meta-hydroxyl group(s)might have poor metabolic stability and suffer from rapid clearance and low oral bioavailability.
文摘During the clinical course of dementia,beside cognitive impairment and memory loss,a very complex challenge is posed by the neuropsychiatric symptoms(NPSs).Accurate evaluation and treatment of pain impacts positively the agitation of demented patients aged ≥ 65 years.To gather information on the utilization of pain killers in demented patients a preliminary survey has been conducted in collaboration with the Calabrian Pharmacovigilance Territorial Service of the health district of Catanzaro(Italy).The study has taken into consideration the prescriptions of acetylcholinesterase inhibitors and memantine during the period ranging from July 2015 to June 2016 and the percentage of patients treated against pain with non steroidal antinflammatory drugs,opioids,and anticonvulsants have been monitored.The latter have been evaluated statistically for difference between the treatment before(pre) and after(post) the settlement of acetylcholinesterase inhibitors(ACh EI) or memantine therapy.The results do support accuracy in painkillers utilization in the course of dementia in the regional population of Calabria(Italy).
文摘The high morbidity generated by the infection caused by parasites of the genus Leishmania, make of this infection into one of the vector-borne infectious diseases most relevant worldwide, which added to the fact that the drugs used for its treatment are far from be optimal and considering that prophylactic approaches (such as the development of a vaccine) still seems far from being achieved, make of the search for new therapeutic alternatives for safe and effective treatment of this disease one of the most accurate approaches to the control of this disease. In this study we evaluated the antileishmanial and immunomodu- latory activity of the compound 11α,19β-dihydroxy- 7-acetoxy-7-deoxoichangin (a seco-limonid molecule) through: 1) evaluation of its cytotoxicity over promastigotes and axenic amastigotes of L. (V) panamensis, 2) determination of its ability to induce the control of in vitro infection, using infected murine cells (J774.2) and human dendritic cells (hDCs), 3) quantifying the levels of pro-inflammatory cytokines, (iv) evaluating the expression of cell markers associated with hDCs maturation, and (v) determinating the production of nitric oxide free radicals (NO). In this regard, this seco-limonoid exhibited an antileishmanial activity represented in the reduction of in vitro infection in J774.2 cells and hDCs, with a EC50 of 7.9 μM (4.48 μg/mL) and 25.5 μM (14.39 μg/mL), respectively, and additionally, we observed an increase on the production of IL-12p70, TNF-α and NO, as also, in the number of hDCs HLA-DR-positive in treated infected hDCs. These findings suggest that anti-lei- shmanial activity of this compound could be associated with the potential “reactivation” of phagocytic cell that is “paralyzed” by the infection, generating an immune phenotype associated with protection.
文摘Cellular and mitochondrial membrane phospholipids provide the substrate for synthesis and release of prostaglandins in response to certain chemical,mechanical,noxious and other stimuli.Prostaglandin D_(2),prostaglandin E_(2),prostaglandin F_(2)α,prostaglandin I_(2)and thromboxane-A_(2)interact with five major receptors(and their sub-types)to elicit specific downstream cellular and tissue actions.In general,prostaglandins have been associated with pain,inflammation,and edema when they are present at high local concentrations and involved on a chronic basis.However,in acute settings,certain endogenous and exogenous prostaglandins have beneficial effects ranging from mediating muscle contraction/relaxation,providing cellular protection,regulating sleep,and enhancing blood flow,to lowering intraocular pressure to prevent the development of glaucoma,a blinding disease.Several classes of prostaglandins are implicated(or are considered beneficial)in certain central nervous system dysfunctions(e.g.,Alzheimer’s,Parkinson’s,and Huntington’s diseases;amyotrophic lateral sclerosis and multiple sclerosis;stroke,traumatic brain injuries and pain)and in ocular disorders(e.g.,ocular hypertension and glaucoma;allergy and inflammation;edematous retinal disorders).This review endeavors to address the physiological/pathological roles of prostaglandins in the central nervous system and ocular function in health and disease,and provides insights towards the therapeutic utility of some prostaglandin agonists and antagonists,polyunsaturated fatty acids,and cyclooxygenase inhibitors.
文摘Background: Vein graft failure after bypass surgery is greatly increase in patients with diabetes mellitus. The cellular mechanisms underlying the cause of this failure are largely unexplored. Protein kinase B/AKT is a mechanically sensitive regulator of cellular growth and apoptosis. Herein we examine whether diabetes affects the regulation of AKT in response to increased venous loading. Methods: Inferior venae cavae (IVC) from the non-diabetic lean (LNZ) and the diabetic obese?syndrome X Zucker(OSXZ) rats were isolated and incubated ex vivo under basal or pressurized conditions (120 mmHg). Protein expression, basal activation and the ability of increased pressure to activate AKT3 and apoptosis-related signaling were evaluated by immunoblot analysis. Results: Compared to that seen in the non-diabetic lean animals, increased venous pressure in the OSXZ rats was not characterized by increases in APAF-1 concentration, XIAP proteolysis, AIF cleavage, or Bad phosphorylation. This evidence of decreased apoptotic signaling was associated with increased basal p-AKT3 levels (+136% ± 13% P < 0.05 higher in the OSXZ vs. LNZ IVC). Conclusion: These data suggest that diabetes-associated increases in p-AKT3 may alter the ability of the IVC to undergo pressure induced apoptosis-related signaling. Further investigation is required to determine whether these changes are associated with the increased vein graft attrition seen in the diabetic population.
文摘Natural products or natural product derived drugs comprised 32% of small molecule approved drugs between 1981 and 2010.In the same period of time,16% of small molecule approved drugs were synthetic or natural mimics based on the study of pharmacophores related to natural products.Indisputably,natural products provide diverse structural diversity and intricate carboskeletal frameworks.As it is believed that nature has evolved optimized biologically active compounds-the secondary metabolites-to ensure survival of the species that produce them,natural products are perceived by some to be more′drug-like′than totally synthetic compounds.As such,natural products may provide us with the′best′lead compounds yet for drug discovery,giving rise to natural product inspired drug design.This talk will provide an overview of some of my research in this area.Specifically,I will outline the challenges and some of the lessons learnt in this quest to develop natural products as leads to potential drugs.