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The Complement System in Systemic Lupus Erythematosus: Overview and Outlook

The Complement system is a participant in many diseases such as paroxysmal nocturnal hemoglobinuria (PNH), hemolytic uremic syndrome (HUS), hereditary angioedema (HAE), etc. Among these rheumatic diseases, systemic lupus erythematosus (SLE) is proved to have the closest relationship with the complement system.

In 1896, Jules Bordet discovered the complement system, and related research earned him the Nobel Prize in Physiology in 1919. At that time, it happened that World War I caused the Nobel Prize to cease for four consecutive years. Jules Bordet became the first recipient of the Physiology Award after the re-award.

After this, complement-related research has experienced many developments and even subversions. Compared to Jules Bordet’s study back then, today’s understanding of complement system is beyond recognition. This article will discuss the relationship between complement and SLE.

Defects in the Complement System Lead to SLE

Congenital defects in the complement system make people more vulnerable to bacterial viruses. This is a major category of congenital immunodeficiency. Interestingly, this not only leads to a decline in resistance to pathogens, but also brings autoimmune diseases.

About 93% of C1q-deficient people will suffer from SLE. Similarly, 75% of those with C4 deficiency and over 30% of those with C2 defects also lead to SLE. Most of the C1r and C1s defecting will also result in SLE. However, due to their low prevalence, it is not appropriate to accurately determine the strength of their association. No stronger innate factors related to SLE have been found. Fortunately, the incidence of such birth defects is low.

Secondary Complement Deficiency and SLE

Bacterial infections, SLE, etc. will cause the level of complement to drop. SLE brings a lot of immune complexes, which combine with complement to cause damage to the body. This is particularly evident in lupus nephritis.

Except that the combination of immune complex and complement leads to the decrease of complement, there are also antibodies against complement. The most widely used is anti-C1q antibody. About 30% of patients with SLE have anti-C1q antibodies, and it is 68% of patients with lupus nephritis. Therefore, a positive anti-C1q antibody indicates a high possibility of lupus nephritis.

Complement-related Drugs and SLE Treatment

The complement system plays an important role in the pathogenesis of many diseases. The pharmaceutical industry has also developed many drugs in a targeted manner.

(1) Eculizumab

Eculizumab is a humanized monoclonal antibody. The antibody binds to complement component 5 and prevents it from cleaving into C5a and C5b, and C5b is necessary to form a membrane attack complex (MAC), which is an important link for complement to participate in body damage, so eculizumab can be used to treat PNH and HUS. However, it is a pity that the clinical practical significance has not been seen in the clinical drug experiments for the treatment of SLE.

(2) Avacopan

The latest major breakthrough in the rheumatology research is Avacopan, a small molecule compound that targets the complement C5a receptor.

Recent clinical randomized double-blind controlled trials have confirmed that Avacopan can successfully replace hormones in combination with other drugs. The biggest problem of this experiment is that the number of cases participating in the experiment is not enough, and the observation time is not long enough. Can Avacopan replace hormones during SLE treatment? There is no reliable clinical controlled trial to verify.

Clinical experience tells us that compared with SLE, ANCA-associated vasculitis tends to rely more on hormones. Since ANCA-associated vasculitis can get out of hormones during treatment, it is possible to look forward to hormone replacement during SLE treatment. The complement therapeutics might the hope of the hormonal-free era of lupus treatment.

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How to win the Game of Auto Loans?

A car gives abundant freedom and happiness to its owner. You get the comfort as well as the ease of driving to the place of your choice. But, buying a car is not very easy. Why? The reason lies in your credit score. If you have a bad credit history, the list of the lenders who will approve your loan application becomes severely restricted. But, everything is not lost. Treat buying a car like a game. And, you can win the game, if you play your cards right!

Rules for winning the Auto Loan Game!

Know your Strength
When you want to win the game and obtain guaranteed auto loan approval, you must understand your strengths. Learn what parts of the loan application will get you in the good books of a lender. Find out your budget. Will you be able to offer a large down payment to the dealer? Is finding a cosigner easy for you? Know how to make the best use of your old car. Find out if selling the car will beneficial to you against trading it for a new one.

Know your Weakness
By knowing your weakness, you will be able to understand to deal with it in a better way. Before the lender surprises you with the news of your bad credit score, you must be ready with a plan. Check your credit score. If there are any unwarranted transactions on the report, send a note to the credit bureaus and begin the process of removing it. If cash is a big constraint for you, avoid making the down payment. Choose an inexpensive used car to negate the need of a down payment.

Find the Right Partner
To win the game of auto loans, you need to find the right partner who will increase your winning chances. When you have bad credit score, work with a reputed auto financing company that doesn’t shy away from offering subprime car loans. Usually, traditional banks choose to finance car buyers with excellent credit scores. And, credit unions offer financing options to their members only. So, online lenders are the best option that remains with you.

Find an online auto financing company that offers you a bad credit auto financing deal. Seek recommendations from your friends and colleagues. Read online review and make an informed decision. Also, do not forget to evaluate the loan quote on several different factors such as interest rate, loan term, loan amount, monthly payment, lender’s reputation, etc. Choosing a reliable lender with easy terms will ensure that you get a fair chance of winning the game of auto loans.

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Marathon Lovemaking Tips – Making it Last

Marathon lovemaking is a great way to break up a couple’s bedroom routine. Sometimes, the busy nature of life and the fatigue it causes end up confining lovemaking to quickies, during which partners tick off their favorite sensual boxes and then wrap it up. Though this may be fun and satisfying for a while, many people dream of a day or night when their escapade leisurely spans several hours. Along with practicing proper manhood care, there are several things men can do to facilitate a successful marathon lovemaking session they and their partners are sure to appreciate. Below, men can find steps to prepare for and last during a marathon session, along with aftercare advice.

Before:

• Self-pleasure daily. Frequent solo play can help a man build stamina in the sack. This is especially true if he implements the technique of edging – bringing himself to the brink of release, backing off, then repeating three or four times before allowing release.
• Exercise. Muscular and cardiovascular strength are important for bedroom endurance. Strong muscles allow a man to hold positions longer, and cardio strength promotes ample blood flow to the male organ, which is necessary for getting and maintaining a wicked hard-on.
• Stock up on lube. Even if one’s partner produces plenty of natural lubrication, it’s bound to run low when a couple is going at it for hours. Have a quality product on hand to make sure lovemaking remains appropriately slick.
• Consider desensitizing barriers. For men who have a hard time lasting, barriers with numbing agents can promote lasting longer without completely deadening pleasure.
• Don’t drink heavily. A drink or two can get one nice and relaxed, but more than that may inhibit tumescence.

During:

• Choose positions wisely. For men with long refractory periods – the amount of time it takes for them to get hard again after releasing – it’s important to choose positions that don’t cause a tremendous amount of stimulation. What positions those are may vary from one man to the next. Also, switching positions regularly can both keep things fresh and allow a guy to last longer.
• Incorporate sensual breaks. It’s not realistic for most people to go at it for hours without any kind of break. Breaks may include a quick snack and hydration, but couples can also incorporate sensual elements to keep both parties fired up and ready for more. This is a great time for a man to orally and manually stimulate his partner, perhaps breaking out some of his partner’s favorite toys.
• Experiment with kinks. Couples with kinks such as bondage can prevent monotony during a marathon session by switching from regular lovemaking to kinky lovemaking. Handcuffs, whips, blindfolds, restraints – the possibilities are endless.

After:

• Wash and moisturize. Once both partners have attained satisfaction from their marathon lovemaking session, it’s time to focus on hygiene and recovery. Washing the naughty bits is a good idea, as is urinating to clear the urethra of any bacteria that may have worked its way in. This is especially important for women to do, since urinary tract infections are more likely to occur if they don’t urinate after lovemaking.

Men may notice that their male organs are sore from the prolonged friction of marathon lovemaking – not to mention the chafing of daily self-gratification. They can care for their skin by making use of a quality male organ health crème (health professionals recommend Man1 Man Oil) after washing their equipment. A product that contains both Shea butter and vitamin E will moisturize the delicate member skin without causing irritation. Vitamin A is another great ingredient, since it can help fight bacteria that causes unwanted odors. Taking proper care of his male organ will allow a man to recover faster and be ready for his next session, whether with hand or partner.

Visit http://www.menshealthfirst.com for additional information on most common male organ health issues, tips on improving organ sensitivity and what to do to maintain a healthy member. John Dugan is a professional writer who specializes in men’s health issues and is an ongoing contributing writer to numerous websites.

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