Fatal road traffic accident statistics for - per , population. Aggregated Statistics For Year Based on 1 full and 4 partial tracts. Approval Date Humira Adalimumab For reducing signs and symptoms and inhibiting the progression of structural damage in adult patients with moderately to severely active rheumatoid arthritis who have had an inadequate response to one or more disease-modifying anti-rheumatic drugs DMARDs. Fasitibant chloride is a nonapeptide antagonist of the bradykinin B2 receptor. The compound was undergoing preclinical investigation in the USA and Brazil.
Icatibant is a selective peptidomimetic bradykinin B2 receptor antagonist originated by sanofi-aventis. However, development of this compound appears to have been discontinued. Fournier Pharma was acquired by Solvay in July ; it is now a wholly-owned subsidiary of Solvay. It was in development with Groupe Fournier in France for the treatment of asthma. Development was at the preclinical stage and the drug was available for licensing.
However, development has been discontinued. Groupe Fournier later changed its name to Fournier Pharma. Studies using NPC have provided evidence for a B3-receptor subtype in airway smooth muscle.
However, the development of NPC appears to have been discontinued. It was at the preclinical stage of development, but no recent development has been reported. No recent development has been reported. It may have potential for the treatment of asthma, septic shock, arthritis and pain. It was undergoing preclinical development with Scios in the US as an anti-inflammatory agent. The compound may also have had potential in the treatment of Gram-negative sepsis, and appeared to be undergoing preclinical evaluation as an antiasthmatic agent.
However, the development of NPC was discontinued. It was at the preclinical stage of investigation with Scios in the USA. The compound was undergoing preclinical investigation in the USA and Brazil. The compound was undergoing preclinical evaluation in the US and Brazil. The development of NPC was discontinued at the preclinical stage. The drug was in phase II clinical trials, but further development has been discontinued.
Kinins are released at sites of tissue injury and produce pain and inflammation via activation of constitutively expressed bradykinin B2 and inducible bradykinin B1 receptors. The B1 receptor has been implicated in the humoral, cellular and neuronal mechanisms underlying chronic inflammatory pain.
Peripherally restricted B1 peptide antagonists are efficacious at reversing neurogenic pain induced by capsaicin as well as inflammatory pain induced by UV irradiation, carageenan, CFA and LPS. Development is at a preclinical stage. Amgen had identified a lead compound AM , an aryl sulfonamide, with high affinity for the B1 receptor. However, the compound had only modest bioavailablity in cats, dogs, and mice. By conducting a structure-activity relationship analysis on the drug candidate, Amgen identified compounds with improved pharmacokinetic values that showed in vivo activity in a rabbit model of pain.
The B1 receptor has low homology across species so the choice of model species was dependant on the candidate's activity at species-specific B1 receptors 4. Bradykinin peptides have been implicated in a variety of pathological and physiological responses, such as inflammation and pain.
B1 receptor expression is induced after inflammation and tissue damage, and agonists of the receptor are known to produce hyperalgesia. Elan is conducting preclinical development in the US. Elan has identified and developed a class of potent pyrazolecarboxamide bradykinin B1 receptor antagonists. Although these pyrazoles exhibited high selectivity for the receptor, many suffered from first pass metabolism.
This problem was solved by the synthesis of 1-phenylpyrazolecarboxamides, and lead to the development of an undisclosed candidate with good potency and activity. ELN , a lead candidate, that has shown good pharmacokinetic properties in rodents and primates and was efficacious in two primate pain models. Oral, SC and IV routes of administration were investigated in these models. Following tissue injury, bradykinin peptides are rapidly produced, resulting in a variety of physiological effects including pain and inflammation.
These effects are mediated by two G-protein coupled receptors B1 and B2, and the B1 receptor is thought to be responsible for inducing pro-inflammatory and painful stimuli. The development of bradykinin B1 receptor antagonists is at the preclinical stage in Germany. Preclinical investigations were ongoing in France.
The lead compound, LF , was identified by Fournier as a highly selective, systematically active non-peptidic B1 receptor antagonist. Another compound, called LF , was identified earlier as a lead compound from a series of B1 receptor antagonists. It was in development with Fournier Pharma for the potential treatment of inflammatory disorders. However, neither compound was listed on Solvay's pipeline of August , and it appears therefore that development was discontinued.
Bradykinin promotes nociceptor activation and hyperalgesia and can sensitise nociceptors following the release of prostaglandins, cytokines and nitric oxide. B1 receptor antagonists have been shown to elicit antinociceptive and antihyperalgesic activity in several models of persistent and visceral pain.
Development is at the early research stage in Hungary. Gedeon Richter has identified and developed a series of phenanthridine derivatives that exhibited low nanomolar affinity for the BK B1 receptor and high selectivity over the BK B2 receptor subtype. The programme was at the discovery stage. In September , Jerini was acquired by Shire. Therefore, it is envisaged that antagonists of this receptor would have therapeutic utility in the treatment of pain.
Bradykinin is an important mediator of hyperalgesia, inflammatory diseases, asthma and cancer. It is a pro-inflammatory polypeptide that can cause pain, inflammation, increased vascular permeability, vasodilation, contraction of various smooth muscles and cell proliferation by stimulating bradykinin-B1 and bradykinin-B2 receptors.
As of September , Biofrontera is evaluating the pharmacokinetics and efficacy of the lead compounds in animal models of inflammatory skin disease.. A lead compound was identified, JSM , and development was at the preclinical stage. The B1 receptor is one of two G-protein coupled receptors found on peripheral and central cell types.
Under pathophysiological conditions such as inflammation or tissue injury, the B1 receptor is upregulated resulting in the release of pain and inflammation mediators. Preclinical development is ongoing in Germany. A number of lead compounds have been identified from the programme, including AZ , from over compounds screened. The aim is to develop a lead compound with improved chemical and metabolic stability as well as water solubility.
Preclinical development is ongoing, with three compounds being trialled in human microdosing studies. Regulatory filings are expected to be made sometime after Previous lead compounds include AZD and AZD , which were undergoing preclinical development for the treatment of neuropathic pain and gastro-oesophageal reflux disease; however it is assumed that development of these compounds have been discontinued in both indications as they were not mentioned in AstraZeneca's general presentation in July Development is at the research stage in Italy.
A consortium led by Axxam is also developing Nav 1. Axxam's partners in the consortium are Newron Pharmaceuticals, Primm srl, and academic groups at the University of Milan Bicocca. The research programme combines the use of Axxam's ion channel drug discovery platform, Primm's expertise in protein expression and peptide chemistry, and Newron's expertise in sodium channel electrophysiology and pain pharmacology. Voltage-gated sodium channels play a crucial role in the initiation and propagation of the action potential, and have been implicated as key constituents in pain signalling.
Activation of the contact system occurs early in patients with sepsis and leads to release of bradykinin and undesired initiation of the coagulation cascade. Bradykinin is a highly pro-inflammatory peptide that induces vascular leakage and a dangerous drop in blood pressure.
HM prevents activation of the contact system, thereby inhibiting the subsequent relase of bradykinin. An additional compound, HM , has also been identified but appears to be a backup compound for HM Preclinical development of the sepsis programme is underway with Hansa in Sweden. Hansa is also developing a diagnostic method, known as HMD , for the diagnosis of severe sepsis prior to the onset of symptoms. Blood samples are taken from patients with mild fever and established or suspected infection, and are screened using immunochemical techniques for a protein secreted by white blood cells.
Early detection of sepsis will enable healthcare professionals to commence antibiotic therapy up to 12 hours before symptoms appear. The HMD method was clinically verified in and is undergoing further technical optimisation.
It was in preclinical development with Servier as a potential antiasthmatic and anti-inflammatory agent, but no recent development has been reported. The compound was also believed to have potential for the treatment of inflammation.
Preclinical investigations of SSR as a potential therapy for CNS disorders, neuropathic pain and inflammation also appeared to have been conducted by sanofi-aventis. However, no recent development of SSR has been reported. Bradykinin B1 receptors are important mediators of chronic inflammation and contribute to the activation of pain processes. Therefore, it is envisaged that a bradykinin B1 receptor antagonist will have therapeutic utility as an anti-inflammatory and analgesic agent.
In August , Sanofi-Synthelabo merged with Aventis to form sanofi-aventis. It is a third generation B2 antagonist, and appears to have potential as an antiasthmatic agent.
In 's , many bradikynin antagonists have been found and investigated, but most of all showed disappointing results. In Japan, bradikynin antagonists have not attracted interests of pharmaceutical companies or medical reserchers in general. In the Ichushi Japan Centra Revuo Medicina , Japan's largest medical literature database, only 50's papers of bradikynin antagonists are included, and most of them are of basic physiological or pharmacological purposes.
Also no bradikynin antagonists have not listed in Japan drug pipeline except Fujisawa's candidates. Fujisawa Now, Astellas Pharm 's research leaders reviewed "Bradykinin antagonist: However, the results were less convincing than expected. Now several potent and orally active nonpeptide B2-receptor antagonists have been found, which are expected to overcome the weak point of the peptide type antagonists and clarify the therapeutic potential of the B2-receptor antagonist for novel indications as well as those mentioned above.
As for B1 receptors, no antagonist has been tested in a clinical trial. Icatibant is not under development in Japan. RA market is still on an Unmet medical needs, but new entry's hurdle is high.
Japan's OA Patients size is small 40, patents , but possible for new medicines. Prescriber Update Articles Vol. EULAR recommendations for the management of early arthritis: EULAR evidence based recommendations for the management of hip osteoarthritis: Osteoarthritis OA , or degenerative joint disease, is the most common form of arthritis.
It most often affects middle-aged and older people, involving the neck, lower back, knees, hips and fingers. Nearly 70 percent of people over the age of 70 have x-ray evidence of the disease, but only half of these people ever develop symptoms.
It may also occur in joints that have suffered previous injury, been subjected to prolonged heavy use, or damaged by prior infection or inflammatory arthritis. Patients with OA experience pain and loss of function. The causes of cartilage loss are multiple. Some kinds of OA are known to be hereditary, including the common form that causes enlargement of the knuckles.
Current research focuses on this genetic abnormality as well as new methods studying cells, chemistry and function of cartilage. These efforts are creating rapid progress in our understanding of OA. In most people, cartilage breakdown is due to both mechanical "wear and tear" effects and biochemical effects. OA is the most common type of arthritis and a leading cause of disability in the U. Virtually everyone over the age of 75 is affected in at least one joint. Women are generally affected at a younger age than men.
It may be confirmed by a physical examination, x-rays and by ruling out other types of arthritis. Since it is so common, it may be present simultaneously with other types of arthritis. Recently, several thick liquids that resemble normal joint fluid have been approved for use by repeated injection in the knee joints.
In addition, there is some evidence suggesting that some dietary constituents may have a beneficial effect. Other therapies include patient education, occupational and physical therapy to restore joint movement and increase strength and aerobic capacity, reduction of weight on painful joints and application of heat and cold to relieve pain.
Joint surgery to repair or replace seriously damaged joints may be required to end pain and restore functional mobility. Because of the high frequency of the disease, physicians in all specialties should participate in the care of people with OA.
Rheumatologists serve as educators to primary care physicians and as team coordinators when the team approach to treatment is necessary. If you want more information on this or any other form of arthritis, contact the Arthritis Foundation at or visit the Arthritis Foundation web site at www.
Mon,Jul5, Carol Eustice - your About. Arthritis You are here: It is usually chronic, meaning that it lasts a lifetime. Specific causes for arthritis are not yet known for most forms of the disease.
The disease process also varies depending on the form of arthritis. The three most prevalent forms are osteoarthritis OA , fibromyalgia and rheumatoid arthritis RA. Osteoarthritis is a degenerative joint disease in which the cartilage that covers the ends of bones in the joint deteriorates, causing pain and loss of movement as bone begins to rub against bone. In fibromyalgia, widespread pain affects the muscles and attachments to the bone.
Rheumatoid arthritis is an autoimmune disease. In RA the joint lining becomes inflamed as part of the body's immune system activity. The chronic inflammation causes deterioration of the joint and the pain and limited movement. The key is early diagnosis and a treatment plan tailored to the needs of each individual. Physicians diagnose arthritis based on the overall pattern of symptoms, medical history, physical exam, x-rays, and lab tests.
Most treatment programs include a combination of medication, exercise, rest, use of heat and cold, joint protection techniques, and sometimes surgery. The three main symptoms of arthritis are joint pain, joint stiffness or inability to move joint normally, and sometimes swelling, that last more than two weeks.
That's one in every six people. Arthritis is one of the most prevalent chronic health problems and the number one cause of limitation in movement in the United States. Anyone can get arthritis - it affects people in all age groups, including as many as , children.
The condition takes an especially heavy toll among women; nearly two-thirds of people with arthritis are women. Arthritis costs the U. Osteoarthritis, fibromyalgia and rheumatoid arthritis are the most prevalent forms of arthritis.
RA, one of the most serious and disabling types of arthritis, affects an estimated 2. Osteoarthritis, or degenerative joint disease, affects an estimated Fibromyalgia affects more than 2 million Americans. Other serious and common forms of arthritis or related disorders include the following: Gout is usually the result of a defect in body chemistry.
This painful condition most often attacks small joints, especially the big toe. Fortunately, gout can almost always be completely controlled with medication and changes in diet. Systemic lupus erythematosus lupus is a serious disorder. It can inflame and damage joints and other connective tissues throughout the body.
Scleroderma is a disease of the body's connective tissue that causes a thickening and hardening of the skin. Ankylosing spondylitis is a kind of arthritis that affects the spine. As a result of inflammation, the bones of the spine grow together. Juvenile arthritis is a general term for all types of arthritis that occur in children.
Children may develop juvenile rheumatoid arthritis or childhood forms of lupus, ankylosing spondylitis or other types of arthritis. How the Arthritis Foundation Helps The Arthritis Foundation offers a variety of programs that can help people with arthritis make life easier and less painful.
The Arthritis Foundation is the source of help and hope for nearly 43 million Americans with arthritis. These are typically from Cobra , Midland , Realistic , or Uniden , which are so new they're not ready yet, or already been published but now out of print.
For these we may have service aids like a schematic or voltage chart. Please write, FAX, or Email for prices. The list is alphabetical by brand or manufacturer. These links jump directly to the brand's letter. EICO Sentinel The original parts can be unmarked or even unreadable, but as long as you have a schematic and are willing to make some phone calls or write, it can be done.
Sacramento, CA — In March, Federal agencies issued the terms and conditions for a new license which include fish ladders and flow improvements to benefit dwindling Klamath River salmon, steelhead and lamprey runs. PacifiCorp is fighting these mandates arguing that suitable habitat for salmon no longer exists upstream of the dams Happy Camp, CA — A recent analysis of water samples from Copco and Iron Gate Reservoirs reveal extremely high levels of the toxic blue-green algae Microcystis aeruginosa which produces a compound known to cause liver failure and promote tumor growth.
Copco reservoir, OR - Recent phytoplankton cell count results for July th and th were received from Aquatic Analysts These data clearly show that hepato-toxic capable of causing chronic liver damage and acting as a tumor promoter blooms of Microcystis aeruginosa MSAE have increased dramatically in intensity and extent Now under new management, the company is starting to listen. Portland, OR - Klamath Basin Tribes and allies from the commercial fishing and conservation organizations will stage a rally at the bi-annual meeting of the international hydropower industry- Hydrovision Happy Camp, CA — In response to a structural fire, which destroyed a ceremonial dance house at the Karuk ceremonial area of Katimin near Somes Bar on July 2, an emergency session of the Karuk Tribal Council was convened last Friday A ceremonial dance house was destroyed and has been deemed a total loss.
The fire is currently under investigation and a cause has not yet been determined. Billionaire investor Warren Buffet intends to work with the Gates Foundation to donate billons of dollars to charity. Orleans, CA — Yesterday Governor Schwarzenegger proclaimed a State of Emergency in 10 Counties providing disaster loan guarantees for salmon fishermen.
Although encouraged by the action, Karuk Tribal members will not see much benefit from the package. Instead of ladders as mandated by the agencies, which the agencies had deemed necessary for success, PacifiCorp seeks to trap fall-run Chinook salmon at Iron Gate dam and drive them 80 miles to Klamath Falls, Oregon. Orleans, CA - The Aquarium Incubator Project provides students, teachers and community members an excellent opportunity to learn about the life cycles and habitat requirements of salmon and trout, important natural resources in the Klamath River Basin.
San Francisco, CA — At a rally.. EPA Regional Administrator Wayne Nastri presented plaques to three dozen organizations and individuals throughout the Pacific Southwest in recognition of their efforts to protect and preserve the environment in Today, the two federal agencies released mandatory terms and conditions for the issuance of a new license for Klamath Dams operated by PacifiCorp.
Happy Camp, CA — In an effort to protect the most critical cold water refugia for salmon, eel, and sturgeon, the Karuk Tribe filed a complaint with California Fish and Game demanding changes to suction dredge mining rules and regulations.
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