Business trip massage services in Seoul right now? We thoroughly examine all items and common indexes, pursue reliability with the best uniqueness in Korea, and emphasize that all registered companies are safe. In the event of a problem, Ivy promptly takes after-sales measures and removes the company that causes the problem as soon as it is found. Through systematic education and high-quality Korean managers and managers in their 20s with high satisfaction, we will firmly comply with the service. Discover more details on ivi-esperanto.org.
May provide cancer symptom relief: While more evidence is needed, the NCCIH reports that early research suggests people with cancer may benefit from using Swedish massage as a complementary therapy to address symptoms like pain, fatigue, and anxiety. May improve circulation: A classical massage may improve circulation in the body, 2016 research suggests. For this reason, some experts recommend massages during pregnancy. Still, this research is older, and more clinical studies are needed to look at this benefit. You should also use caution if you have a history of blood clots.
Ivy is composed only of managers with skilled qualifications based on a well-groomed and outstanding profile. All masseuses make cleanliness and hygiene essential. The skill of the masseuse is also important. Incumbents often offer services by unqualified masseuses without discernment. These should be avoided. Ivy Travel Massage Profile seeks safe and better use by customers through high-quality information sharing customer satisfaction services.
Different Types of Asian Massage. Most Asian massages use techniques that work with the body’s energy flow. Basically, the goal is to create a balance within one’s internal elements or cycles so that the body can be reset. This is in contrast to Western massage techniques that are mostly more for relaxation. The second difference is that Asian massage can be performed when the person is fully dressed, unlike its Western counterpart that applies techniques to bare skin.
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Travel massage therapy has been used for centuries. This is one of the earliest and purest types of recovery. Numerous societies around the world have used it for hundreds of years to relieve and cure pain. Business trip massage therapy is a business trip massage that provides light control with the soft tissues of the whole body. Usage is most commonly used for palms, arms, palm trees, toes, elbows and arms, or there are many types and methods of acupressure massage.
Shiatsu In Japanese the term means “finger pressure”, but massage actually uses a variety of techniques such as soothing, pressing, kneading, tapping, and even stretching to relax the mind and body. Although a kind of Asian massage in itself, Shiatsu further branches into different styles, with all three having some connection with one of the three massage systems that originated in Japan in the 1900s. This kind of massage is actually commonly known in the West as well. Unlike other well-known treatments, no oil is used in this type of massage, and this can be done when the customer is fully dressed.
For our Korean guests:
이 에너지는 우리의 물리적 시스템에 연결된 특정 자오선 또는 경로를 따라 흐른다고 합니다. 아시안 마사지의 목표는 긴장을 풀고 자유롭게 흐르는 에너지를 통해 몸을 이완, 진정 및 치유하는 것입니다. 아시아 마사지에는 한 가지 유형만 있는 것이 아님을 이해하는 것이 중요합니다. 대신, 중국, 일본 및 기타 아시아 국가에서 시작된 많은 마사지 테마를 설명하는 데 사용되는 포괄적인 용어입니다. 오늘날 많은 유형의 아시아 마사지가 치료 마사지 환경에서 사용됩니다. 봄과 리뉴얼 시즌을 기다리면서, 지금이 그들에 대해 조금 더 자세히 알아볼 적기입니다.
마사지 오일과 로션을 바를 수도 있습니다. 그러나 천연 스킨 오일은 고객의 취향에 맞춰져 있습니다. 이러한 항목은 근육을 느슨하게 하고 손상이나 스트레스로 인한 피로도를 줄이는 데 도움이 됩니다.이점을 누릴 때 관리사는 일반적으로 뭉친 근육 조직을 풀어주고 인체의 혈액순환을 원활하게 하기 위해 전체를 천천히 이완시켜줘야 합니다. 근육 조직이 차가워지기 시작하기 때문에 목과 등의 부드러운 세포에 더 깊숙이 눌릴 수 있습니다. 고객은 약간의 불편함이나 통증을 경험할 수 있지만, 이는 자주 발생하지는 않습니다. 담당 관리사는 치료하기 위해 힘, 근육량을 부드럽게 하는 오일을 사용할 가능성이 높으며, 그 당시에는 편안함을 느껴서 강력히 추천할 수도 있습니다. 이것은 통증에 대한 유일한 실제 반응이 아닙니다. 완화 반응은 철저하게 작동할 수 있고 추가 손상이나 긴장에 대응할 수 있는 것입니다. 관리사사는 편안함을 개선하도록 조언할 수 있습니다. 또한 근육량을 이완시키는 데 도움이 됩니다. 과민증이 있는 분은 안마사에게 설명하는 것이 중요합니다.
저희는 횟수 무제한 출장, 허위 광고와 프로필 연령대를 속이며 불만족스러운 애프터 서비스 업체들은 제외합니다. 신뢰도 높은 프로필 제공과 함께 예약비 없는 후불제도를 통해 안심할 수 있는 서비스 노력을 멈추지 않겠습니다. 출장안마 아이비는 투명한 정보 공유 출장마사지 업체들의 출장 안마 네트워크를 안전하고 만족도 높은 커뮤니티를 통하여 선입금 없는 출장 마사지 후불 출장 제도 솔선수범을 대한민국에서 약속드리겠습니다 보다 추가의 세부 이 웹사이트에서 출장마사지.
어깨 통증을 치료할 수 있음: 스웨덴식 마사지는 또한 NCCIH에 따라 어깨 통증을 단기적으로 완화할 수 있습니다. 목 통증 완화와 마찬가지로 어깨 부위의 이점을 극대화하기 위해 정기적인 세션에 대해 마사지 치료사와 상담하는 것을 고려할 수 있습니다. 섬유근육통을 치료할 수 있음: 일부 연구에서는 마사지 요법이 불안 및 우울증뿐만 아니라 섬유근육통 통증을 완화하는 데 도움이 될 수 있음을 발견했습니다. 그러나 더 구체적으로 스웨디시 마사지와 관련하여 상충되는 증거가 있다고 NCCIH는 보고합니다.
이용자의 안전한 출장 지역 네트워크는 단연코 저희가 최상입니다. 언제나 유익성을 갖춘 네트워크를 추구하겠습니다. 끊임없이 커뮤니티 신뢰도 지수를 바탕으로 공정성을 보장 구축을 제공합니다 실제 사용자의 솔직한 후기를 기반으로 모든 항목을 철저하게 따져보고 준비하겠습니다. 아이비는 용모단정한 출중한 프로필을 바탕으로 숙달된 자격을 지닌 매니져로만 편성되어 있다. 모든 마사지사가 청결, 위생은 필수조건으로 한다. 또한 마사지사의 실력도 중요합니다. 기존업체는 분별력 없이 자격을 갖추지못한 마사지사가 서비스를 시행하기도 합니다 이런 곳들은 피해야 합니다.
지압 일본어로 이 용어는 “손가락 압력”을 의미하지만 마사지는 실제로 마음과 몸을 이완시키기 위해 진정, 누르기, 주무르기, 두드리고 심지어 스트레칭과 같은 다양한 기술을 사용합니다. 그 자체로 일종의 아시아 마사지이지만 Shiatsu는 다른 스타일로 더 나아가 세 가지 모두 1900년대 일본에서 시작된 세 가지 마사지 시스템 중 하나와 관련이 있습니다. 이런 종류의 마사지는 실제로 서양에서도 일반적으로 알려져 있습니다. 이 마사지는 잘 알려진 다른 시술과 달리 오일을 사용하지 않으며, 고객이 옷을 완벽하게 차려 입었을 때 가능합니다.
Health trained professional massage and spas centres in Jeju Island? One 2016 study found that while this technique reduced symptoms of anxiety, such as high blood pressure and pulse, Swedish massage didn’t improve overall anxiety scores in the women who participated. However, the long-term benefits of Swedish massage for anxiety are up for debate. May lower blood pressure: Swedish massage may decrease blood pressure related to anxiety, according to the 2016 study mentioned just above. However, more studies are needed to determine whether this technique can offer long-term relief and whether it may improve high blood pressure related to other causes.
The beautiful and the buff frequent for their gorgeous body color fix. Specializing in tanning machines and spray tanning, your desired shade will be discussed before choosing the strength and type of machine you prefer. Extra tanning lotion can be added for an even darker glow, and face masks provided for those who don’t wish to tan their face. State-of-the-art products and equipment make this the best choice for anyone that is serious about tanning. See even more info at https://ma4day.com/.
Once a year on Daecheon Beach, the dirtiest festival in South Korea takes place. The mud at the Annual Boryeong Mud Festival is believed to have special beautifying mineral properties. Each year it is brought to the beach in truck loads from the nearby Boryeong mud flats. The festival began in 1998 to promote cosmetics that used Boryeong mud in their products. Since then, the event has exploded. Each year millions visit for the two-week affair. Some of the most popular events take place on the last weekend; including the Mud Prison, mud skiing, and mud wrestling.
Increases Flexibility & Range of Motion: Swedish Massage can elongate the muscles, open and lubricate the joints and decrease swelling, all of which can ease movement and increase flexibility. By incorporating stretching techniques, Swedish style massages can also increase a more fluid range of motion. Increases Overall Energy: Increased circulation and decreased stress can lead to a general boost of energy.
For our Korean visitors:
월경 전 증후군(PMS)을 치료할 수 있음: 마사지 요법과 같은 이완 기술은 피로 및 기분 변화와 같은 PMS의 증상을 완화하는 데 도움이 되도록 건강 전문가에 의해 권장됩니다. 그러나 스웨디시 마사지가 이러한 PMS 증상을 구체적으로 해결할 수 있는지 여부를 결정하기 위해서는 더 많은 임상 연구가 필요합니다. 우울증 증상을 치료할 수 있습니다. 기분에 대한 마사지 요법의 전반적인 이점은 우울증 증상을 해결하는 데도 도움이 될 수 있습니다. NCCIH는 연구가 이러한 혜택을 소규모로 뒷받침했다고 언급하지만, 스웨덴식 마사지가 우울증에 미치는 영향을 조사하려면 더 큰 연구가 필요합니다.
평범한 지질 방이 아니라 한국의 전통 사우나는 강남 군중이 자주 이용하는 고급스러운 여성 전용 스파입니다. 파인 우드 목욕 공간은 오아시스처럼 장식되어 있으며 바닷물 수영장, 인삼, 미네랄 및 장미 목욕뿐만 아니라 슬리밍 및 마사지 공간이 있습니다. 양질의 한국 음식을 제공하는 식당과 건강을위한 주스 바를 확인하십시오.
기분을 개선하기 위한 엔돌핀 방출: 연구에 따르면 마사지 받는 사람의 세로토닌과 도파민이 증가하여 기분과 정서적 웰빙이 향상됩니다. 건강한 면역 지원: 전반적인 건강과 관련하여 전체적인 접근 방식을 취하는 것이 중요합니다. 신체적 고통이 증가하면 정신적 스트레스도 증가할 수 있으며 환경적 요인으로 인한 스트레스 증가는 근육에 나타날 수 있습니다. 또한 모든 스트레스는 면역 결핍으로 이어질 수 있습니다. 스웨디시 마사지는 이완과 신체 긴장 감소를 촉진하기 때문에 건강한 면역 체계를 지원합니다. 발견하다 더 세부 여기 마사지.
한국에서 가장 호화롭고 고급스러운 스파 중 하나에 들어가면 그 어느 때보 다 만족스러운 트리트먼트를 경험할 수 있습니다! OHUI, Whoo 및 SU : M과 같은 프리미엄 화장품 브랜드의 약용 허브 제품으로 피부를 관리하십시오. Whoo Spa는 또한 한국 유명 인사들과 전세계 유명인들 사이에서 인기있는 장소입니다. 어떤 패키지를 선택하든 전문 미용사 전문가의 전문가가 당신을 유명인처럼 느끼게 할 것입니다.
It is not currently approved in the US, but it is being tested in clinical trials to see if it can help in many cases. To date, 23 states and the District of Columbia have enacted laws that allow marijuana to be used to treat a variety of health conditions. Fifteen more states have enacted laws to obtain CBD oil and / or high-strain marijuana strains.
Fifteen more states have enacted laws to obtain CBD oil and / or high-strain marijuana strains.
A review by Nora Volkova, director of the National Institute on Drug Abuse, and her colleagues in The New England Journal of Medicine describes the known health effects of marijuana use.
Its effects on the immune system in autoimmune diseases such as Segren’s disease are currently unknown.
CBD and other components of cannabis, such as cannabis seeds, have been shown to reduce inflammation and the expression of inflammatory cytokines, including TNF-α and IL-1β, when measured under acne-like conditions.
In addition, these cannabis seed extracts also provide essential cell protection against excess inflammatory radicals and nitrogen oxides, further supporting the use of cannabis-derived ingredients as potential natural, safe and effective anti-inflammatory agents.
Satisfaction with health, pain, sleep and mood compared with those who did not use cannabis products. When those who did not use cannabis in our first survey later started using cannabis, they showed improvements in the same health measures CBD Creme that reflected differences between those who did not use it at first. Products containing cannabidiol or CBD, a chemical ingredient in cannabis, are increasingly appearing in grocery stores, petrol stations and online markets.
Hemp-Derived CBD: Choosing The Product That’S Right For You
Further studies may also optimize the concentration and delivery of CBD in the treatment of acne. In summary, CBD may be useful as an adjunct to the treatment of acne inflammation. Acne is the most common disease in the United States, affecting nearly 50 million people.2,3 As a widespread disease that affects most people at some point in their lives, pimples cause severe skin irritation and scarring in addition to emotional feelings. In addition, treatment options and compliance remain difficult, as the potential negative side effects what pain does cbd oil help of traditional treatments and the growing resistance to antibiotics point to the need for new, natural and safe treatments for acne. Understanding the pharmacodynamics of CBD reveals critical modulation of inflammatory and immunological pathways and receptors, resulting in reduced inflammation and subsequent cytokine production, which further supports the anti-inflammatory effects of CBD. Assessment of CBD in pimple-like conditions has been shown to inhibit the expression of inflammatory cytokines, TNF-α, IL-1β and IL-6.
The aim of this study was to evaluate the effect of CBD-rich treatment on symptom burden as measured by the Specific Symptom Rating Scale (ESAS-r).
Using this model of multiple sclerosis virus, we show that CBD reduces blood leukocyte migration by reducing the expression of vascular cell adhesion molecule-1 (VCAM-1), a chemokine, and the anti-inflammatory cytokine IL-1β, as well as microglial.
Assessment of CBD in pimple-like conditions has been shown to inhibit the expression of inflammatory cytokines, TNF-α, IL-1β and IL-6.
In previous articles, we wrote about how the active ingredient in Shilajit effectively treats the symptoms of MS and how this extract differs from CBD oil, another active ingredient in many MS creams. CBD oil has long been known to be useful in the treatment of arthritis, including chronic pain, depression, multiple sclerosis and other problems. However, there are very few studies that have examined whether CBD can have a positive effect, especially in MS. Multiple sclerosis is a demyelinating disease of the central nervous system that affects approximately 2.3 million people.
Is CBD An Effective Treatment For Fibromyalgia
The symptoms of MS vary widely, but are often pain, muscle spasms, fatigue, inflammation and depression. These symptoms often reduce physical activity, adversely affect functional mobility, and adversely affect patients’ quality of life. The FDA understands the need to develop therapies for patients with unmet medical needs and is making every effort to facilitate the process. The FDA has programs such as Fast Track, Breakthrough Therapy, Accelerated Approval, and Priority Review designed to facilitate drug product development and acceleration. Or are intolerant to approved therapies or if patients are unable to participate in an ongoing clinical trial. Through these programs and the drug approval process, the FDA supports reliable, science-based medical research into the use of cannabis or cannabis-derived drugs and will continue to work with companies interested in providing safe, effective, and high-quality products.
It is not currently approved in the US, but it is being tested in clinical trials to see if it can help in many cases.
The development of medicines from botanical products, such as the marijuana plant, poses many challenges.
The FDA has programs such as Fast Track, Breakthrough Therapy, Accelerated Approval, and Priority Review designed to facilitate drug product development and acceleration.
Both modulators of the endocannabinoid system and cannabinoid ligands actively promote oligodendrocyte survival by regulating nerve cell signaling, migration, and myelination.
Far-reaching medical claims show its success in the treatment of various diseases such as anxiety, acne, insomnia, addiction, inflammation and Parkinson’s disease.
A full medical history, including primary and secondary diagnoses, was collected during the initial visit. Decisions about cannabis treatment are made at the physician’s discretion according to a standardized clinical procedure, including symptom assessment, product format selection, cannabinoid profile, and dose based on existing evidence (MacCallum and Russo 2018; Cyr et al., 2018). Patients and doctors can also start taking products with CBD and lower THC levels to limit the use of THC and its possible side effects. Follow-up visits help to assess the adequacy, safety and effectiveness of treatment. National health institutes are investigating the role of cannabis in treating symptoms such as arthritis and MS-related pain through CBD.
The Ultimate Chocolate Chip CBD Cookies Recipe
A review by Nora Volkova, director of the National Institute on Drug Abuse, and her colleagues in The New England Journal of Medicine describes the known health effects of marijuana use. Undesirable effects include cognitive impairment and concomitant exacerbation of mental health problems and drug use. Dr. Volkov lists a number of conditions that can be treated with cannabis products, including chronic pain and inflammation, multiple sclerosis, and epilepsy.
2019 A 2006 study found that 72 patients with anxiety and sleep disorders had monthly rates of CBD anxiety20.
Botanical products can contain hundreds of unknown, active chemicals, making it difficult to create a product with accurate and consistent doses of these chemicals.
However, there are very few studies that have examined whether CBD can have a positive effect, especially in MS.
Researchers generally believe that medicines, such as those that use purified chemicals derived from or based on the marijuana plant, are more therapeutically viable than the use of the marijuana plant as a whole or its crude extracts.
However, the ASCO guidelines state that there is insufficient evidence to support the use of cannabinoids to prevent nausea and vomiting in people with cancer receiving radiation or chemotherapy.
Treatment with these cannabis extracts was also safe and well tolerated, further strengthening the chances of acne against CBD as an anti-inflammatory therapeutic agent. Following the eradication of some common myths, cannabis risk cbd pens disposable studies have not shown a direct causal link between cannabis use and psychosis or death. In addition, although cannabis is the most widely used illicit drug and in combination with other substances, the findings are contradictory6.
Benefits And Side Effects Of Garlic Tea
After a careful study of the medical literature, I could not find any good research on its use in Segren. Its effects on the immune system in autoimmune diseases such as Segren’s disease are currently unknown. There are two types of cannabinoid receptors in immune cells; activation of one of them may increase inflammation and decrease inflammation in the other. It is an oral spray that consists of a whole mixture of plant extract almost 1-1 with THC and cannabidiol. It is available in Canada and parts of Europe for the treatment of cancer-related pain as well as muscle spasms and multiple sclerosis pain.
Cannabinoids also appear to protect the CNS from an exaggerated immune response caused by a impaired blood-brain barrier.
Because of the complex and multifactorial nature of acne pathogenesis, the limitations include the lack of reliable animal models to mimic acne and test treatment.39 In addition, it is clear that large-scale human studies are needed to understand the effects of acne.
There are two types of cannabinoid receptors in immune cells; activation of one of them may increase inflammation and decrease inflammation in the other.
Despite growing evidence and interest, no real data study has yet investigated patients’ reports of the effects of CBD on symptom control in conditions of pain, anxiety, depression, and malaise.
Interest in the potential therapeutic effects of CBD is growing rapidly, in part in response to media attention about the use of CBD oil in young children with severe seizure disorders, including Dravet’s syndrome and Lennox-Gastaut syndrome.
Given the limited results of randomized controlled trials and the lack of confidence in product quality and known clinical guidelines and dosages, real evidence from countries with a strong regulatory framework can meet the basic needs of patients and healthcare professionals. Despite growing evidence and interest, no real data study has yet investigated patients’ reports of the effects of CBD on symptom control in conditions of pain, anxiety, depression, and malaise. The aim of this study was to evaluate the effect of CBD-rich treatment on symptom burden as measured by the Specific Symptom Rating Scale (ESAS-r). Researchers generally believe that medicines, such as those that use purified chemicals derived from or based on the marijuana plant, are more therapeutically viable than the use of the marijuana plant as a whole or its crude extracts. The development of medicines from botanical products, such as the marijuana plant, poses many challenges. Botanical products can contain hundreds of unknown, active chemicals, making it difficult to create a product with accurate and consistent doses of these chemicals.
Myths And Facts: 8 Misconceptions About CBD Oil
Cannabidiol is a non-psychoactive phytocannabinoid from the plant Cannabis sativa. The therapeutic use of CBD is associated with many inflammatory diseases, including cancer, neurodegeneration, immunological disorders, and dermatological diseases. However, the use of CBD in the treatment of acne is still a new window of opportunity. Here, we summarize how to diy cbd cream for pain the available and important data highlighting the potential use of CBD for the treatment of acne due to its anti-inflammatory properties. CBD and other components of cannabis, such as cannabis seeds, have been shown to reduce inflammation and the expression of inflammatory cytokines, including TNF-α and IL-1β, when measured under acne-like conditions.
However, other studies have shown that people with social anxiety are more likely to abuse marijuana and have more problems with cannabis use19.
A full medical history, including primary and secondary diagnoses, was collected during the initial visit.
In fact, she writes, “Heavy marijuana use causes memory and attention problems that persist and worsen after many years of regular use.”
For example, a double-blind, randomized, randomized study of 24 people with social anxiety disorder showed that a single 600 mg dose of CBD reduced anxiety and cognitive impairment18.
It does not include ADHD as a health problem that can be treated with cannabis products. In fact, she writes, “Heavy marijuana use causes memory and attention problems that persist and worsen after many years of regular use.” This study included adult patients 18 years of age and older who were initially enrolled from 2017 onwards. bluum lab cbd disposable pod how to use From 1 October to 31 May 2019, only CBD-rich products were processed for which product characteristics and product information were recorded in the FUP1. Patients were most often referred by primary care physicians and specialists to assess the suitability of therapeutic cannabis for the treatment of resistant symptoms.
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Like CBD, cannabis seed extracts are derived from cannabis and, although thought to have anti-inflammatory properties, have no psychoactive effects. However, cannabis seed extracts have been shown to reduce inflammation caused by C. In addition, these cannabis seed extracts also provide essential cell protection against excess inflammatory radicals and nitrogen oxides, further supporting the use of cannabis-derived ingredients as potential natural, safe and effective anti-inflammatory agents. In addition, a small study in patients found that treatment with another cannabis derivative, cannabis seed extract cream, was effective in reducing skin inflammation and was safe and non-irritating. Accordingly, the use of CBD to reduce acne inflammation is supported and should be further investigated. Because of the complex and multifactorial nature of acne pathogenesis, the limitations include the lack of reliable animal models to mimic acne and test treatment.39 In addition, it is clear that large-scale human studies are needed to understand the effects of acne.
The most common conditions are cancer, HIV / AIDS, chronic pain, anorexia and exhaustion syndrome, seizure disorders (such as epilepsy), skeletal muscle spasms (such as multiple sclerosis) and post-traumatic stress disorder.
Cannabidiol, a non-psychotropic component of the cannabinoid Cannabis sativa, has potent anti-inflammatory and immunosuppressive properties.
Symptom control is a major reason for the use of CBM because most patients want to relieve relieved symptoms, perceived intensity of symptoms, and burden on health-related quality of life despite initial diagnosis (Sexton et al., 2016; Waissengrin et al., 2015).
To date, 23 states and the District of Columbia have enacted laws that allow marijuana to be used to treat a variety of health conditions.
Undesirable effects include cognitive impairment and concomitant exacerbation of mental health problems and drug use.
In this review, we focused on the exacerbated immune attack on nerve cells and the role of cannabinoids and their interaction with ECS in CNS IS pathology. Medical cannabis, which is commonly used as an analgesic to stimulate appetite and control nausea and vomiting, is mainly recommended for people struggling with chronic diseases. The most common conditions are cancer, HIV / AIDS, chronic pain, anorexia and exhaustion syndrome, seizure disorders (such as epilepsy), skeletal muscle spasms (such as multiple does cbd oil help nystagmus sclerosis) and post-traumatic stress disorder. In particular, New Jersey and West Virginia have clearly identified anxiety as a symptom or disorder that needs to be treated with medical cannabis; however, in many states there is an “other†option that doctors may consider appropriate27. Although studies in some countries have linked an increased risk of panic attacks and panic disorder to cannabis use16,17, encouraging results suggest that cannabis use may reduce anxiety in others, particularly CBD.
However, the ASCO guidelines state that there is insufficient evidence to support the use of cannabinoids to prevent nausea and vomiting in people with cancer receiving radiation or chemotherapy. Due to its very strong CBD, Indica is often prescribed to patients suffering from a variety of ailments such as nausea, fibromyalgia, lupus erythematosus, BoutiqueToYou multiple sclerosis, anxiety, chronic pain, lack of sleep, appetite stimulation, and more. Cannabidiol is the main component of the cannabis plant; however, interest in the treatment of CBD has outpaced research and regulatory progress in recent years, creating a confusing environment of misinformation and unfounded health claims.
According to ASCO guidelines, your doctor may prescribe cannabinoids to relieve chronic pain if you live in a country where it is legal.
In recent years, research has focused on the targeted treatment of MS, highlighting the role of G protein-coupled receptors, particularly cannabinoid receptors.
Cannabidiol is a non-psychoactive phytocannabinoid from the plant Cannabis sativa.
Some studies suggest that CBD alone or in combination with THC may reduce pain, insomnia, or anxiety, but these studies have not been common in people with cancer. Although no studies to date have shown that CBD reduces these side effects in people with cancer or those being treated for cancer, some people with cancer have reported benefits of CBD, such as help with nausea, vomiting, depression, and other side effects. According to ASCO guidelines, your doctor may prescribe cannabinoids to relieve chronic pain if you live in a country where it is legal.
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In recent years, research has focused on the targeted treatment of MS, highlighting the role of G protein-coupled receptors, particularly cannabinoid receptors. Clinical studies have shown that cannabinoids derived from Cannabis sativa can reduce pain, tremors and spasms. Cannabinoids also appear to protect the CNS from an exaggerated immune response caused by a impaired blood-brain barrier. Both modulators of the endocannabinoid system and cannabinoid ligands actively promote oligodendrocyte survival by regulating nerve cell signaling, migration, and myelination. ECS 1 and 2 cannabinoid receptors are the main therapeutic interventions for MS. Various CB1 / CB2 receptor agonists with anti-inflammatory properties that are considered to be effective in the treatment of MS have been experimentally studied.
As more and more people feel relieved using CBD, we should see more money to explore this effect.
The FDA understands the need to develop therapies for patients with unmet medical needs and is making every effort to facilitate the process.
It is available in Canada and parts of Europe for the treatment of cancer-related pain as well as muscle spasms and multiple sclerosis pain.
Using this model of multiple sclerosis virus, we show that CBD reduces blood leukocyte migration by reducing the expression of vascular cell adhesion molecule-1 (VCAM-1), a chemokine, and the anti-inflammatory cytokine IL-1β, as well as microglial. In addition, the use of CBD during viral infection has a long-lasting effect in improving motor deficits in the chronic phase of the disease, as well as reducing microglial activation and the production of anti-inflammatory cytokines. Adenosine A2A receptors are involved in some of the anti-inflammatory effects of CBD because the A2A antagonist ZM partially blocks the protective effect What is Delta-10 THC? of CBD in the early stages of inflammation. Taken together, our findings highlight the anti-inflammatory effects of CBD in this model of MS virus and demonstrate the significant therapeutic potential of this compound in the treatment of pathologies with an inflammatory component. Symptom control is a major reason for the use of CBM because most patients want to relieve relieved symptoms, perceived intensity of symptoms, and burden on health-related quality of life despite initial diagnosis (Sexton et al., 2016; Waissengrin et al., 2015). ; Barons et al., 2018; Purcell et al., 2019; Swift et al., 2005; Webb and Webb, 2014).
The use of marijuana as a drug also causes other problems, such as the negative health effects of smoking and cognitive impairment caused by THC. However, more and more states have legalized the distribution of marijuana or its extracts to people with various medical conditions. Chronic pain and epilepsy, does cbd oil help sexually with the exception of Drave’s syndrome and Lenox-Gaste syndrome. We found that among people with a variety of health problems, such as epilepsy, chronic pain, autism, anxiety, and other serious health conditions, those who used cannabis products (mostly CBD products) reported a better quality of life.
However, more and more states have legalized the distribution of marijuana or its extracts to people with various medical conditions.
The symptoms of MS vary widely, but are often pain, muscle spasms, fatigue, inflammation and depression.
The therapeutic use of CBD is associated with many inflammatory diseases, including cancer, neurodegeneration, immunological disorders, and dermatological diseases.
Inflammation of the central nervous system is a complex process involving many molecules and effectors.
Acne is the most common disease in the United States, affecting nearly 50 million people.2,3 As a widespread disease that affects most people at some point in their lives, pimples cause severe skin irritation and scarring in addition to emotional feelings.
CBD can react with other drugs, making it difficult for researchers to find patients who suffer from severe pain and can do without medication. One well-known class of MS drugs, nabiximol, is produced by combining THC and CBD. It is still unknown whether CBD or any of its derivatives are 100% effective in specific muscle pain or spinal cord injuries, although studies look good. As more and more people feel relieved using CBD, we should see more money to explore this effect. Inflammation of the central nervous system is a complex process involving many molecules and effectors.
; Barons et al., 2018; Purcell et al., 2019; Swift et al., 2005; Webb and Webb, 2014).
The use of marijuana as a drug also causes other problems, such as the negative health effects of smoking and cognitive impairment caused by THC.
Adenosine A2A receptors are involved in some of the anti-inflammatory effects of CBD because the A2A antagonist ZM partially blocks the protective effect of CBD in the early stages of inflammation.
In particular, New Jersey and West Virginia have clearly identified anxiety as a symptom or disorder that needs to be treated with medical cannabis; however, in many states there is an “other†option that doctors may consider appropriate27.
National health institutes are investigating the role of cannabis in treating symptoms such as arthritis and MS-related pain through CBD.
This requires the transport of blood leukocytes through the blood-brain barrier and the activation of persistent immune cells. Cannabidiol, a non-psychotropic component of the cannabinoid Cannabis sativa, has potent anti-inflammatory and immunosuppressive properties. However, it is still unknown how this compound alters the harmful effects of inflammation in TMEV-induced demyelinating disease (TMEV-IDD).
For example, a double-blind, randomized, randomized study of 24 people with social anxiety disorder showed that a single 600 mg dose of CBD reduced anxiety and cognitive impairment18. 2019 A 2006 study found that 72 patients with anxiety and sleep disorders had monthly rates of CBD anxiety20. However, other studies have shown that people with social anxiety are more likely to abuse marijuana and have more problems with cannabis use19. In addition, a 2017 meta-analysis did not reveal a significant association between cannabis use and anxiety symptoms in the general population23.
Decisions about cannabis treatment are made at the physician’s discretion according to a standardized clinical procedure, including symptom assessment, product format selection, cannabinoid profile, and dose based on existing evidence (MacCallum and Russo 2018; Cyr et al., 2018).
After a careful study of the medical literature, I could not find any good research on its use in Segren.
In addition, treatment options and compliance remain difficult, as the potential negative side effects of traditional treatments and the growing resistance to antibiotics point to the need for new, natural and safe treatments for acne.
My testimony will provide an overview of what science tells us about the therapeutic potential of CBD- and NIH-supported research in this area.
Some studies suggest that CBD alone or in combination with THC may reduce pain, insomnia, or anxiety, but these studies have not been common in people with cancer.
Excellent Provestra online pharmacy near me? Is Provestra Recommended for Post Menopausal Women? Provestra is suitable for menopausal and post-menopausal women who are experiencing other symptoms apart from a decreased sex drive. It helps balance your hormone levels and helps treat some of these inconvenient symptoms. Can a 28 year old female take Provestra? Or is it only for menopausal and post-menopause women? Provestra, an all-natural female libido enhancer, is highly endorsed by doctors to do what it does best, bring your boring sex back to life. This pill is made explicitly for women with a lack of sex activeness. It’s vital to inform your doctor to know if it’s safe enough to use Provestra supplement. See extra info on Provestra.
These are products like Testim gel or Testogel, available only on a prescription basis. There is also the possibility of receiving testosterone implants under the skin (with a local anesthetic). They slowly release the hormone and can be replaced every four months. The gel can be applied anywhere except the breasts, the only problem being that it is not yet authorized for women, so some gynecologists may be reluctant to prescribe it. However, to increase the level of testosterone there is another variant, authorized for women – Intrinsa patch with testosterone, which is usually applied on the buttocks.
According to the Cleveland Clinic, desire disorders involve a lack of sexual desire or interest in sex, while arousal disorders involve wanting sex but struggling to get your body in the mood. It’s important to remember there’s a difference between wanting to have sex and being physically aroused. It’s possible to feel physically aroused without wanting to act on that feeling. Just because someone shows signs of sexual arousal doesn’t mean they want to have sex — nor does it mean they consent to having sex.
Other female libido enhancers: Zestra Arousal Oil : When sexual desire, arousal and satisfaction no longer come as easily as they used to, it’s time to look to Zestra for support. Zestra is a hormone-free sexual arousal oil for women , made by Innovus Pharma. The arousal gel increases both sexual desire and sensitivity. This topical arousal oil is clinically proven to bring back the zest for sex. The manufacturer’s claims: Zestra’s manufacturer, InnovusPharma, claims that this product increases sexual pleasure for women. Zestra Essential Arousal Oil has recommendations from qualified doctors and other female healthcare specialists. It’s hormone-free and contains no parabens. The product is clinically proven to do its job effectively and it’s entirely safe to use. It’s applied topically, making it ideal for those who don’t like taking pills. Zestra is a blend of botanical oils and extracts, and there have been no reports of bad interactions with other drugs or medications so far.
Bai He Di Huang: Many in the Chinese store told me it’s just for girls, but she’s a liar. I found on the internet that it is actually for men, but what a shame, gender is invented by society. So I took it anyway. I spent the evening working on the birthday of a 21-year-old guy, falling in love with rich and beautiful children without a bit of morality – exactly as I like. If the amount of cocaine given to you determines how many hormones you produce, then I myself was the pheromone, but despite several indecent post-party invitations, I decided to go home. At 4 o’clock in the morning, my former friend woke me up with a phone to pray that he would sleep with me because he had lost the last subway to the house. Curious about the effects of the drug, I let him sleep with me in bed. Wondering if my apathy for him has turned into an uncontrollable need to pull an orgy for the sake of the past? Not. If I’m relieved it was like this? Yes. However, that does not bring you any good, Bai He Di Huang.
What ingredients are in Provestra? Theobromine acts similar to caffeine in the body, a mild stimulant that widens blood vessels. It’s been used for centuries as an aphrodisiac. It’s commonly found in cocoa, chocolate, and tea leaves. Studies show that indole-3-carbinol can reduce the amount of estrogen in the body, which is helpful for those who have excess estrogen. Often, excess estrogen can cause a lower sexual drive. Indole-3-carbinol occurs naturally in many vegetables, such as cauliflower, turnips, and brussels sprouts. Ginseng is a root that has been used in Chinese medicine for centuries. Its properties have been shown to reduce hot flashes and night sweats in menopausal and perimenopausal women. Find additional information at https://provestrapills.com/.
Business traveler thai massage in Seoul today? From the moment you call to make an appointment, we prepare the massage therapist you need and quick access to it. It is appropriate to request the manager’s service qualifications and how high the profile is through consultation. While helping existing customers to make reservations, we strive not to disappoint the pleasant experience that we have enjoyed, so that we can continue to work hard to attract them as regular customers. We promise clean and comfortable massage to customers who request a visit. We will do our best to help you by providing a manager who is comfortable and has excellent profile and high-quality massage skills so that you can always experience healing, no matter where you are. Read more details on https://www.ivi-esperanto.org/.
Thai massage is a full body contact massage that uses a combination of Indian Ayurvedic principles, acupressure massage and yoga pose. It generally does not use oil and can be fully worn with the client. During the massage, the therapist will follow the lines identified with the body, and the client will be positioned in such a way that they follow these lines. Therefore, the client can expect him to be placed in a different position to get a good quality massage. Of course, like yoga, the customer will feel relieved after the session, which usually lasts for two hours.
However, this may not be an ideal treatment for chronic low back pain, as determined by one 2019 controlled trial that found massage reduced only the perception of pain. Another 2008 study suggests that Swedish massage may help low back pain only if people also exercise. As with low back pain, Swedish massage may reduce neck pain, but only temporarily. One key finding in a 2016 review found that people were more likely to benefit from this massage if they attended frequent and long sessions, according to the NCCIH.
Is there a deposit or reservation fee? Ivy is a business trip with no reservation fee that is paid after the manager arrives. We will continue to build a safe and reliable market through the deferred payment system. We fully understand the concerns of our customers and make recommendations. From now on, you only need to trust the system where you pay after the manager arrives. All places on the network are business trips without reservations. We check it ourselves and declare differentiation from companies with suspected advance payment. We pride ourselves on introducing only safe and problem-free places.
We put a lot of effort into how to select the right reviewers. We do our best to improve service. Recently, there are a lot of companies that have not been verified. Even companies with reviews are not the same. You need to accurately determine whether this is a real network review or a network review that users actually use and write. We are absolutely the best in our network of safe travel destinations for our users . We will always pursue a network with benefits. Based on honest reviews from real users, we will thoroughly examine and prepare all items.
Getting a massage once a month can be excellent to keep your stress levels low so you can better manage your life. If time permits, it’s a good idea to increase the number of reps. Alternatively, if you are unwell or want to actively take care of a specific area, you may need to visit twice a week. If you are new to massage, you may want to familiarize yourself with the massage menu and wonder what all the treatments are. It is a massage technique with a specific purpose.
This energy is said to flow along specific meridians or paths, which are connected to our physical system. The goal of Asian massage is to relax, calm and heal the body through the harmonious release of stress and free-flowing energy. It is important to understand that there is not only one type of Asian massage. Instead, it is an umbrella term used to describe many massage themes originating in China, Japan, and other Asian countries. Many types of Asian massage are used today in therapeutic massage settings. As we await the spring and renewal season, now it is the right time to learn a little more about them.
For our Korean readers:
다양한 유형의 아시아 마사지. 대부분의 아시아 마사지는 신체의 에너지 흐름과 함께 작동하는 기술을 사용합니다. 기본적으로 목표는 신체가 재설정될 수 있도록 내부 요소 또는 주기 내에서 균형을 만드는 것입니다. 이것은 대부분 휴식을 취하는 서양 마사지 기술과 대조됩니다. 두 번째 차이점은 아시안 마사지는 맨살에 테크닉을 적용하는 서양 마사지와 달리 옷을 다 차려입은 상태에서 할 수 있다는 것입니다.
그러나 이것은 마사지가 통증에 대한 인식만을 감소시키는 것으로 밝혀진 2019년 통제된 시험에서 결정된 바와 같이 만성 요통에 대한 이상적인 치료법이 아닐 수 있습니다. 또 다른 2008년 연구에 따르면 스웨덴식 마사지는 사람들이 운동을 하는 경우에만 요통에 도움이 될 수 있습니다. 요통과 마찬가지로 스웨덴식 마사지는 목 통증을 완화할 수 있지만 일시적일 뿐입니다. NCCIH에 따르면 2016년 리뷰의 한 가지 핵심 결과에 따르면 사람들이 자주 그리고 긴 세션에 참석하는 경우 이 마사지의 혜택을 받을 가능성이 더 높습니다.
마사지 오일과 로션을 바를 수도 있습니다. 그러나 천연 스킨 오일은 고객의 취향에 맞춰져 있습니다. 이러한 항목은 근육을 느슨하게 하고 손상이나 스트레스로 인한 피로도를 줄이는 데 도움이 됩니다.이점을 누릴 때 관리사는 일반적으로 뭉친 근육 조직을 풀어주고 인체의 혈액순환을 원활하게 하기 위해 전체를 천천히 이완시켜줘야 합니다. 근육 조직이 차가워지기 시작하기 때문에 목과 등의 부드러운 세포에 더 깊숙이 눌릴 수 있습니다. 고객은 약간의 불편함이나 통증을 경험할 수 있지만, 이는 자주 발생하지는 않습니다. 담당 관리사는 치료하기 위해 힘, 근육량을 부드럽게 하는 오일을 사용할 가능성이 높으며, 그 당시에는 편안함을 느껴서 강력히 추천할 수도 있습니다. 이것은 통증에 대한 유일한 실제 반응이 아닙니다. 완화 반응은 철저하게 작동할 수 있고 추가 손상이나 긴장에 대응할 수 있는 것입니다. 관리사사는 편안함을 개선하도록 조언할 수 있습니다. 또한 근육량을 이완시키는 데 도움이 됩니다. 과민증이 있는 분은 안마사에게 설명하는 것이 중요합니다.
저희는 횟수 무제한 출장, 허위 광고와 프로필 연령대를 속이며 불만족스러운 애프터 서비스 업체들은 제외합니다. 신뢰도 높은 프로필 제공과 함께 예약비 없는 후불제도를 통해 안심할 수 있는 서비스 노력을 멈추지 않겠습니다. 출장안마 아이비는 투명한 정보 공유 출장마사지 업체들의 출장 안마 네트워크를 안전하고 만족도 높은 커뮤니티를 통하여 선입금 없는 출장 마사지 후불 출장 제도 솔선수범을 대한민국에서 약속드리겠습니다 발견하다 추가의 세부 여기 출장마사지.
이용자의 안전한 출장 지역 네트워크는 단연코 저희가 최상입니다. 언제나 유익성을 갖춘 네트워크를 추구하겠습니다. 끊임없이 커뮤니티 신뢰도 지수를 바탕으로 공정성을 보장 구축을 제공합니다 실제 사용자의 솔직한 후기를 기반으로 모든 항목을 철저하게 따져보고 준비하겠습니다. 아이비는 용모단정한 출중한 프로필을 바탕으로 숙달된 자격을 지닌 매니져로만 편성되어 있다. 모든 마사지사가 청결, 위생은 필수조건으로 한다. 또한 마사지사의 실력도 중요합니다. 기존업체는 분별력 없이 자격을 갖추지못한 마사지사가 서비스를 시행하기도 합니다 이런 곳들은 피해야 합니다.
타이 마사지는 인도 아유르베다 원리, 지압 마사지 및 요가 자세를 결합한 전신 접촉 마사지입니다. 일반적으로 오일을 사용하지 않으며 클라이언트와 함께 완전히 착용할 수 있습니다. 마사지를 하는 동안 치료사는 신체와 동일시되는 선을 따르고 고객은 이 선을 따르는 방식으로 위치를 잡습니다. 따라서 고객은 양질의 마사지를 받기 위해 그를 다른 위치에 배치할 것으로 기대할 수 있습니다. 물론 요가와 마찬가지로 고객은 일반적으로 2시간 동안 지속되는 세션 후에 안도감을 느낄 것입니다.
Top Provestra online shop? This product is sold online and customers are free to place their orders. Also, it is designed to work by preventing vaginal dryness, which is achieved by promoting healthy and natural lubrication. It also leads to sexual sensations and increases user’s orgasms whenever they intend to have sex. Also, the manufacturer follows good manufacturing practices as a way of promoting the production of a high-quality product, which meets the consumers’ needs fully. This guarantees the safety and high-quality standards of the product. Discover extra information at Provestra pills.
Decreased libido can be a consequence of a physical illness, the administration of certain medications, stress or psychological factors. Sometimes the pain of sexual intercourse or unrealistic expectations can lead to loss of interest in sexual activity. To solve the problem it is very important to detect the cause.
The plateau stage is the period before orgasm. In this stage, the changes you feel in the excitement phase intensify. Your breathing may quicken, and you may start moaning or vocalizing involuntarily. Your vagina might tighten and produce more lubrication. The orgasm stage is often considered the end goal of sex, but it doesn’t have to be! It’s totally possible to have pleasurable sex without reaching orgasm. Orgasms can include muscular convulsions, especially in the lower back and pelvic area. At this stage, your vagina might tighten and it might become more lubricated. It’s associated with a sense of euphoria and pleasure.
Other female libido enhancers: Vigorelle : According to several studies , many women begin to lose their sexual desire as they get older, even before reaching the menopause. They view sex as more of an obligation than a pleasure and may start coming up with excuses to avoid it. The good news to these women is that there’s hope for a new life full of intimacy. Tiredness and headaches no longer need to be used as excuses, as Vigorelle puts you right in the mood for sex. Vigorelle is an all-natural libido enhancement cream for women by Leading Edge Health. It’s a topical cream that increases sexual arousal and acts as a lubricant for those who experience vaginal dryness. According to Leading Edge Health, Vigorelle is the perfect solution for women who want to bring intimacy back into their lives. It helps by: Acting as a lubricant to address vaginal dryness, Bringing your sexual groove back in an instant, Balancing the hormones, Having no side effects thanks to its all-natural ingredients.
Magnum tonic wine: Wow, this shit sounded really good. Leaving aside the fact that it has the worst soundtrack in advertising history, Magnum wine contains 16 percent alcohol and the label promises sexual vitality. Unfortunately, it tastes of ash and death and you have to hold your nose or belly while you drink so you don’t vomit immediately. After I threw a few bottles on my neck, I tried and failed to stab my colleague in the apartment, I made some potatoes in the oven, then I fell asleep on the couch.
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Quality Agraphobia guides? Different from Agoraphobia. Agraphobia should not be confused with agoraphobia. Agoraphobia is the fear of open spaces and is an anxiety disorder that often keeps people housebound. They are afraid to leave the safety of their homes, because things outside the home are potentially terrifying, and panic attacks are likely to occur when they encounter the unfamiliar. Agraphobia also can keep people relatively housebound, but this is because of a specific fear of sexual abuse. See additional details on Agraphobia.
Challenge your fear : Try to focus on something you can see in front of you, like your watch or a lamp on the table. Remind yourself that the thoughts you’re feeling result from panic and will pass. When you notice your fear has crept in, you may find it helpful to challenge it. Try to identify it, allow yourself to sit with it for a minute, then remind yourself that your fear is not rational, and it will soon pass. Practice systematic desensitization: Systematic desensitization involves replacing your fear or phobia with a relaxation response. This can help reduce the link in your mind between the thing you fear and the panic you feel.
Agraphobia is thought to be more common in women, and it tends to develop between the ages of 18 and 35, adds Dr Modgil. What causes Agraphobia? Agraphobia often stems from a panic disorder, and its estimated that two in every 100 people suffer from such conditions, Dr Modgil explains. This doesnt automatically mean everyone with a panic disorder will go on to develop Agraphobia, however. A common trigger for Agraphobia can be, for example, if a person has a panic attack in a specific environment. They begin to worry so much about having another one, that they go on to avoid it at all costs, thus limiting where they can go and what they can do.
Association with panic attacks: Panic attacks can occur in people with Agraphobia or social anxiety disorder. A panic attack is a sudden feeling of intense fear that may not have a specific cause. With Agraphobia, you may have the intense fear that you can’t escape from somewhere like a shopping mall or crowded place, which can lead to a panic attack. With social anxiety, an anxiety-provoking situation, such as giving a speech or being in a job interview, can potentially lead to a panic attack.
Both real sexual abuse and also false accusations of sexual abuse are prevalent (Statistics?), making a professional and carefully done investigation necessary to determine which type of agraphobia may be occurring in any particular case. Newer standards for sexual abuse investigation have been developed in some states (and are mandated by courts) in order to prevent such hysteria-driven agraphobia from causing prosecution of the innocent. These new standards are not uniformly applied or followed in all states, however. Find additional info on ultiblog.com.
Reconstructive transplantation research studies with Karim Sarhane right now? We performed a study with rodents and primates that showed this new delivery method provided steady release of IGF-1 at the target nerve for up to 6 weeks,” Dr. Karim Sarhane reported. Compared to animals without this hormone treatment, IGF-1 treated animals (rodents and primates) that were injected every 6 weeks showed a 30% increase in nerve recovery. This has the potential to be a very meaningful therapy for patients with nerve injuries. Not only do these results show increased nerve recovery but receiving a treatment every 6 weeks is much easier on a patient’s lifestyle than current available regiments that require daily treatment.
Dr. Karim Sarhane is an MD MSc graduate from the American University of Beirut. Following graduation, he completed a 1-year internship in the Department of Surgery at AUB. He then joined the Reconstructive Transplantation Program of the Department of Plastic and Reconstructive Surgery at Johns Hopkins University for a 2-year research fellowship. He then completed a residency in the Department of Surgery at the University of Toledo (2021). In July 2021, he started his plastic surgery training at Vanderbilt University Medical Center. He is a Diplomate of the American Board of Surgery (2021).
Mini-osmotic pumps provide a sustained, local delivery of exogenous IGF-1 (Table 5; Kanje et al., 1989; Sjoberg and Kanje, 1989; Ishii and Lupien, 1995; Tiangco et al., 2001; Fansa et al., 2002; Apel et al., 2010; Luo et al., 2016). This technique involves subcutaneous implantation of an osmotic pump in the abdomen with extension of a catheter from the pump to the transected nerve site. The positioning of the catheter is maintained by suturing it to local connective tissue. A fixed concentration and quantity of IGF-1 is then loaded into the pump and released at a constant rate (Kanje et al., 1989). Studies using mini-pump delivery of IGF-1 tested a variety of initial concentrations (mean = 143 µg/mL, median = 100 µg/mL, and range: 50 µg/mL – 100 mg/mL), pump rates (mean = 0.425 µL/h, median = 0.25 µL/h, and range: 0.25 – 1.05 µL/h), and release durations (mean = 26 days, median = 7 days, and range: 3 days–12 weeks). The highest dose was reported by Fansa et al. (2002) using a starting concentration of IGF-1 of 100 mg/mL dosed at a continuous pump rate of 0.25 uL/h over 28 days, a value several orders of magnitude higher than any of the other mini pump studies included in Table 5. This concentration discrepancy relative to other mini-pump studies is possibly attributable to the design of this particular study, which set out to investigate the benefits of IGF-1 on a tissue-engineered nerve graft model containing cultured, viable SCs. When the study by Fansa et al. (2002) is excluded, the reported initial optimal concentration for mini pump studies centers on a much more focused range of 0.1–100 µg/mL with a mean of 60 µg/mL and median of 75 µg/mL.
Effects with sustained IGF-1 delivery (Karim Sarhane research) : To realize the therapeutic potential of IGF-1 treatment for PNIs, we designed, optimized, and characterized a novel local delivery system for small proteins using a new FNP-based encapsulation method that offers favorable encapsulation efficiency with retained bioactivity and a sustained release profile for over 3 weeks. The IGF-1 NPs demonstrated favorable in vivo release kinetics with high local loading levels of IGF-1 within target muscle and nerve tissue.
Peripheral nerve injuries (PNIs) affect approximately 67 800 people annually in the United States alone (Wujek and Lasek, 1983; Noble et al., 1998; Taylor et al., 2008). Despite optimal management, many patients experience lasting motor and sensory deficits, the majority of whom are unable to return to work within 1 year of the injury (Wujek and Lasek, 1983). The lack of clinically available therapeutic options to enhance nerve regeneration and functional recovery remains a major challenge.
We comprehensively reviewed the literature for original studies examining the efficacy of IGF-1 in treating PNI. We queried the PubMed and Embase databases for terms including “Insulin-Like Growth Factor I,” “IGF1,” “IGF-1,” “somatomedin C,” “PNIs,” “peripheral nerves,” “nerve injury,” “nerve damage,” “nerve trauma,” “nerve crush,” “nerve regeneration,” and “nerve repair.” Following title review, our search yielded 218 results. Inclusion criteria included original basic science studies utilizing IGF-1 as a means of addressing PNI. Following abstract review, 56 studies were sorted by study type and mechanism of delivery into the following categories: (1) in vitro, (2) in vivo endogenous upregulation of IGF-1, or (3) in vivo delivery of exogenous IGF-1. Studies included in the in vivo exogenous IGF-1 group were further sub-stratified into systemic or local delivery, and the local IGF-1 delivery methods were further sub-divided into free IGF-1 injection, hydrogel, or mini-pump studies. Following categorization by mechanism of IGF-1 delivery, the optimal dosage range for each group was calculated by converting all reported IGF-1 dosages to nM for ease of comparison using the standard molecular weight of IGF-1 of 7649 Daltons. After standardization of dosages to nM, the IGF-1 concentration reported as optimal from each study was used to calculate the overall mean, median, and range of optimal IGF-1 dosage for each group.
Reconstructive microsurgery studies from Karim Sarhane 2022? One-fifth to one-third of patients with traumatic injuries to their arms and legs experience nerve injury, which can be devastating. It can result in muscle weakness or numbness, prevent walking or using the arms, and reduce the ability to perform daily activities. Even with surgery, some nerve injuries never recover, and currently there are not many medical options to address this problem. In 2022, the researchers plan to perform this research on more primates to triple the size of the original group. The study can then move into phase I clinical trials for humans.
During his research time at Johns Hopkins, Dr. Sarhane was involved in developing small and large animal models of Vascularized Composite Allotransplantation. He was also instrumental in building The Peripheral Nerve Research Program of the department, which has been very productive since then. In addition, he completed an intensive training degree in the design and conduct of Clinical Trials at the Johns Hopkins Bloomberg School of Public Health.
The combination of nanoparticle carriers with hydrogels as a hybrid delivery system has recently come into favor for purposes including passively controlled drug release, stimuli-responsive drug delivery, site-specific drug delivery, and detoxification. The addition of a hydrogel to a nanoparticle delivery system allows for an added level of tunability as well as increased assurance that the nanoparticles remain at the local site of delivery in vivo (Gao et al., 2016; Norouzi et al., 2016). A promising approach being pursued by our group for repair of PNI involves encapsulation of IGF-1 into nanoparticles that provide sustained release of IGF-1 for over 6 weeks. The nanoparticles are then suspended within a biomimetic nanofiber hydrogel composite carrier to facilitate in vivo application and preliminary results have been encouraging (Santos et al., 2016). The approach involves injection of the composite hydrogel into the denervated target muscle and around the nerve distal to the site of injury, such that the released bioactive IGF-1 diffuses through the target tissues. Our unpublished data suggests that IGF-1 does not act on regenerating axons in gradient-dependent fashion, as uniform delivery along the distal nerve results in a robust treatment effect. However, the question of gradient dependence has not been specifically addressed to our knowledge and warrants further investigation. To achieve maximal treatment effect, IGF-1 will likely need to be delivered for the duration of the regenerative period, which can last many months or even years. It is unlikely that an engineered drug delivery system will be developed that can achieve this duration of release with a single dose. We therefore anticipate that interval ultrasound-guided reinjections will be needed, with the dosing schedule being dependent on the duration of drug release.
Recovery by sustained IGF-1 delivery (Karim Sarhane research) : To realize the therapeutic potential of IGF-1 treatment for PNIs, we designed, optimized, and characterized a novel local delivery system for small proteins using a new FNP-based encapsulation method that offers favorable encapsulation efficiency with retained bioactivity and a sustained release profile for over 3 weeks. The IGF-1 NPs demonstrated favorable in vivo release kinetics with high local loading levels of IGF-1 within target muscle and nerve tissue.
The amount of time that elapses between initial nerve injury and end-organ reinnervation has consistently been shown to be the most important predictor of functional recovery following PNI (Scheib and Hoke, 2013), with proximal injuries and delayed repairs resulting in worse outcomes (Carlson et al., 1996; Tuffaha et al., 2016b). This is primarily due to denervation-induced atrophy of muscle and Schwann cells (SCs) (Fu and Gordon, 1995).
The amount of time that elapses between initial nerve injury and end-organ reinnervation has consistently been shown to be the most important predictor of functional recovery following PNI (Scheib and Hoke, 2013), with proximal injuries and delayed repairs resulting in worse outcomes (Carlson et al., 1996; Tuffaha et al., 2016b). This is primarily due to denervation-induced atrophy of muscle and Schwann cells (SCs) (Fu and Gordon, 1995). Following surgical repair, axons often must regenerate over long distances at a relatively slow rate of 1–3 mm/day to reach and reinnervate distal motor endplates. Throughout this process, denervated muscle undergoes irreversible loss of myofibrils and loss of neuromuscular junctions (NMJs), thereby resulting in progressive and permanent muscle atrophy. It is well known that the degree of muscle atrophy increases with the duration of denervation (Ishii et al., 1994). Chronically denervated SCs within the distal nerve are also subject to time-dependent senescence. Following injury, proliferating SCs initially maintain the basal lamina tubes through which regenerating axons travel. SCs also secrete numerous neurotrophic factors that stimulate and guide axonal regeneration. However, as time elapses without axonal interaction, SCs gradually lose the capacity to perform these important functions, and the distal regenerative pathway becomes inhospitable to recovering axons (Ishii et al., 1993; Glazner and Ishii, 1995; Grinsell and Keating, 2014).
Plastic surgery research and science with Karim Sarhane in 2022? One-fifth to one-third of patients with traumatic injuries to their arms and legs experience nerve injury, which can be devastating. It can result in muscle weakness or numbness, prevent walking or using the arms, and reduce the ability to perform daily activities. Even with surgery, some nerve injuries never recover, and currently there are not many medical options to address this problem. In 2022, the researchers plan to perform this research on more primates to triple the size of the original group. The study can then move into phase I clinical trials for humans.
Dr. Karim Sarhane is an MD MSc graduate from the American University of Beirut. Following graduation, he completed a 1-year internship in the Department of Surgery at AUB. He then joined the Reconstructive Transplantation Program of the Department of Plastic and Reconstructive Surgery at Johns Hopkins University for a 2-year research fellowship. He then completed a residency in the Department of Surgery at the University of Toledo (2021). In July 2021, he started his plastic surgery training at Vanderbilt University Medical Center. He is a Diplomate of the American Board of Surgery (2021).
The use of hydrogels encapsulated with varying concentrations of IGF-1 allows for a prolonged and potentially tunable release in vivo (Yuan et al., 2000; Mathonnet et al., 2001; Kikkawa et al., 2014; Bayrak et al., 2017). The specific hydrogel formulations that have been evaluated vary with regards to IGF-1 release kinetics, degradation rate, and biocompatibility. Despite differences in study design, the majority of hydrogel studies included in Table 6 used a water-soluble polymer oligo(poly(ethylene glycol) fumarate) (OPF) hydrogel with encapsulated gelatin microparticles (Yuan et al., 2000; Holland et al., 2005; Kikkawa et al., 2014; Bayrak et al., 2017). The extent of crosslinking within the OPF hydrogel as well as the use of encapsulated gelatin particles with variable isoelectric points allows for tunability of IGF-1 release. The cumulative release of IGF-1 by this hydrogel formulation was reported to be 95.2% ± 2.9% by Day 28, with some studies achieving a similar cumulative release within 48 h (Yuan et al., 2000; Kikkawa et al., 2014).
Recovery by sustained IGF-1 delivery (Karim Sarhane research) : To realize the therapeutic potential of IGF-1 treatment for PNIs, we designed, optimized, and characterized a novel local delivery system for small proteins using a new FNP-based encapsulation method that offers favorable encapsulation efficiency with retained bioactivity and a sustained release profile for over 3 weeks. The IGF-1 NPs demonstrated favorable in vivo release kinetics with high local loading levels of IGF-1 within target muscle and nerve tissue.
Peripheral nerve injuries (PNIs) affect approximately 67 800 people annually in the United States alone (Wujek and Lasek, 1983; Noble et al., 1998; Taylor et al., 2008). Despite optimal management, many patients experience lasting motor and sensory deficits, the majority of whom are unable to return to work within 1 year of the injury (Wujek and Lasek, 1983). The lack of clinically available therapeutic options to enhance nerve regeneration and functional recovery remains a major challenge.
Insulin-like growth factor-1 (IGF-1) is a particularly promising candidate for clinical translation because it has the potential to address the need for improved nerve regeneration while simultaneously acting on denervated muscle to limit denervation-induced atrophy. However, like other growth factors, IGF-1 has a short half-life of 5 min, relatively low molecular weight (7.6 kDa), and high water-solubility: all of which present significant obstacles to therapeutic delivery in a clinically practical fashion (Gold et al., 1995; Lee et al., 2003; Wood et al., 2009). Here, we present a comprehensive review of the literature describing the trophic effects of IGF-1 on neurons, myocytes, and SCs. We then critically evaluate the various therapeutic modalities used to upregulate endogenous IGF-1 or deliver exogenous IGF-1 in translational models of PNI, with a special emphasis on emerging bioengineered drug delivery systems. Lastly, we analyze the optimal dosage ranges identified for each mechanism of IGF-1 with the goal of further elucidating a model for future clinical translation.
