Home Authors Posts by Cristian Mihon

Cristian Mihon

137 POSTS 5 COMMENTS

4643

Scientists Can Demonstrate Type 2 Diabetes Susceptibility By DNA Mapping

A team of researchers led by Dr. Asaf Hellman from the Hebrew University of Jerusalem conducted a study according to which they found the molecular risk factors which are leading to type 2 diabetes, thus leading to better measurements to detect patients at high risk of developing type 2 diabetes and at high risk of developing other diseases.

Although numerous studies have been conducted on the molecular basis for disease susceptibility, this subject is still poorly understood.  The scientists found out that the cause of type 2 diabetes susceptibility is represented by epigenetic variations. This epigenetic variations are small molecular marks superimposed on the DNA structure which can modify the predisposition of one person to certain diseases.

The design of this study is involving the analysis of epigenetic variations  which lead to a higher susceptibility of developing type 2 diabetes among people who have relatives suffering from type 2 diabetes mellitus. This study was published in the Human Molecular Genetic, a scientific journal and was presented at the Genomic Center of Cambridge University.

For this study  researchers team decided to map DNA methylation variation among 1,169 type 2 diabetes patients and in non-diabetic patients, who represented the control group. The result of this mapping is that patients who presented a higher risk for developing type 2 diabetes are having a specific DNA methylation signature, thus revealing the epigenetic risk factors for developing type 2 diabetes.

DNA mapping

DNA mapping

DNA methylation is a protective mechanism which regulates enzymes and genes that are involved in the DNA replication process, thus protecting the replication of DNA so that no errors occur while copying the information on DNA strands. DNA methylation is one of the epigentic  regulatory process, in which an alteration in gene expression will not change the nucleotide sequence in the DNA.  The alteration of this regulatory process can lead to some certain diseases in humans.

The analysis of DNA methylation using DNA mapping revealed, for the first time, that in patients with a high risk of developing type 2 diabetes is present a epigenetic signature. This analysis also revealed that in younger individuals who can develop in the future glucose metabolism conditions, in the DNA structure appear specific markers of methylation, before the appearence of clinical manifestation of diabetes.

This research is very important because can lead to a better understanding of individual susceptibility of type 2 diabetes and can represent a starting point in understanding and elucidating the predisposition for other human diseases which have a similar mechanism, like metabolic, autoimmune and psychiatric diseases. Because epigentic marks are sensitive to a wide range of environmental factors, like chemical exposure, diet, intrauterine factors and some therapeutic drugs, the findings of this study can represent a way to understand and to realize a more efficient prevention of certain chronic diseases and maybe in the future the medical world will be able to develop epigenetic therpaies.

4946

Weight Loss Can Be Predicted By Nervous System Activity

According to a new study, researchers from Australia found that people who successfully lose weight have a significantly higher sympathetic nerve resting activity, compared to the people who tried to loss weight but have not succeeded. This study was accepted to be published in Journal of Clinical Endocrinology & Metabolism. In this study were included obese volunteers who participated in a 12 week  dietary weight loss program.

The peripheral nervous system consists of nerves and ganglia outside of the brain and spinal cord, which main role is to connect the central nervous system to the organs and to the limbs. A important part of peripheral nervous system is represented by the autonomic nervous system, a system of control, that is functioning below the level of consciousness and controls organ functions, like digestion, heart rate, salivation, breath rate, perspiration, urination, diameter of the pupils and sexual arousal. Most actions of autonomic nervous system are involuntary, but some actions like breathing can became conscious. The autonomic nervous system is divided into parasympathetic nervous system and sympathetic nervous system.

Weight Loss

Weight Loss

The sympathetic nervous system is regulating, below the level of consciousness, physiological functions which include the consumption of calories after a food intake and the resting metabolic rate. With this study, the scientist try to examine if exists a connection between weight loss and sympathetic nervous system in obese people who are on a low-calorie dietary program.

Lead author of the study, Nora Straznicky, PhD, at Baker IDI Heart and Diabetes Institute in Melbourne, Australia said that they were able to demonstrate for the first time that between weight loss and sympathetic nervous system there actually is a connection and the resting muscle sympathetic nerve activity is a independent predictor of weight loss. She also added that this findings can provide two opportunities. First is represented by the fact that physicians can now identify overweight or obese patients who can lose weight by changeing their lifestyle, such as dieting. The second opportunity is represented by the fact that in the near future the scientists can develop weight loss treatments which can stimulate this specific nervous activity.

The study included 42 obese individuals who participated in a 12 week  dietary weight loss program that cut their daily caloric intake by 30 percent, for a period of 12 weeks. The researchers measured the resting muscle sympathetic nerve activity by microneurography, a procedure that introductes microelectrodes into nerve bundles. Measuring the activity of sympathetic nervous system, the scientists concluded that weight loss can be predicted by the resting muscle sympathetic nerve activity.

5015

Protective Memory Cells Against Autoimmunity Discovered By Scientists

A new type of immune system cells were discovered by scientists at University of California, San Francisco. The role of these cells, after they activated in tissues is to help the immune system differentiate between self structures and non-self body structures therefore preventing autoimmunity.

The discovery can be regarded as a starting point for future research regarding a wide range of autoimmune disorders. Autoimmunity is defined as the inability of the immune system to recognize body’s self molecules and structures leading to a mistakenly attack against them. Transplant rejection is another undesirable consequence of the immune system response.

Scientists from University of California, San Francisco presented their results in the November 27 online edition of the journal Nature

The new type of cells that were studied by researchers at the USCF are in fact counterparts of the memory cells that help fight pathogens after the immunization process.

Immunologist Abul Abbas, Michael Rosenblum, MD, PhD and Iris Gratz, PhD conducted a study on a mouse model in order to highlight the exact role of activated T regulatory cell in the immune system memory. The researchers discovered that, the protection of mouse’s skin of the against autoimmunity is determined by only a part of the T regulatory cells.

Is is actually a new way of understanding how the immune response works. Tissues posses their own immunological memory. Subsequent exposure to the same molecule that triggered the autoimmune response may lead to a decreased inflammatory response, according to Abbas.

In the United States alone, about fifty million people are affected by autoimmune disorders and scientists and medical professionals until now, have blamed only lymphocytes as primary cause of disease. For example in multiple sclerosis, myelin sheath is attacked by antibodies produced by lymphocytes. But the UCSF research team findings suggest that in many cases, autoimmunity can be also attributed to an abnormal response of the T regulatory cells.

Activated T Cell

Activated T Cell

Recently, scientists realized that T regulatory cells can not only prevent the onset of autoimmunity but can decrease its harmful effects too. Based on the same idea Abbas, Gratz and Rosenbum were curious regarding the success rate of desensitization shots in patients suffering from allergies. The procedure uses gradually elevated repeated shots with the known allergen in order to achieve desensitization of the patient and relieve allergy symptoms.

A new genetically engineered strain of mice were created by the USCF researchers, in which they could inhibit a certain protein synthesis, in the epithelium – ovalbumin. An autoimmune response was then achieved after the mice were forced to produce an excess amount of ovalbumin. On the other hand , ovalbumin also triggered the activation of T regulatory cells. A better suppression of the autoimmune response was achieved after the multiplication of T regulatory cells which became more potent with this occasion. Afterwards the researchers triggered again an overabundance of ovalbumin production but it led to a much weaker autoimmune response. The result was attributed to the already activated T regulatory cells.

The discovery of activated T regulatory cells (also called long-lived memory cells) can help in the future prevent attacks against specific ‘antigens’ as in the case of type 1 diabetes and multiple sclerosis.

5556

Genetic Breakthrough Stops Skin Cancer

An amazing breakthrough in halting skin cancer could be the starting point of new cancer treatment options and methods of prevention, available in just five years.

In a study published yesterday in the Cancer Cell international journal, a multinational team has discovered a squamous cell cancer protective gene. The scientist team is led by Professor Stephen Jand and Dr Charbel Darido.

About two in three new cases of skin cancer are diagnosed in Australians before reaching the age of 70. squamous cell cancer is by far the most frequent type diagnosed. Until lately the exact genetic mechanism of squamous cell carcinoma was not fully understood and the surgical excision being pretty much the only treatment option.

Skin Cancer

Skin Cancer

A very important gene, involved in fetal skin development is not present in squamous cell carcinoma cells. This particular gene is also lacking in other tissues where squamous cell carcinoma develops including neck cancer which usually has a bad prognosis. almost all squamous cell carcinomas that were examined by scientists lacked or had almost undetectable levels of the gene. Absence or lack of the gene is therefore a profound cause of these type of cancers, concluded the scientists.

The mechanism by which tumor growth in encouraged by the gene was explained by investigating its exact role (signals the skin cells to stop growing). This skin cancer driver can provide a new treatment target for future research programs. On the other hand some drugs that can be used effectively for treating squamous cell carcinoma are already available and just need to be applied in neck or skin cancer patients. This skips potential long research, testing and drug approval periods and patients could benefit from this new discovery in just five years.

On the other hand, prevention could be also achieved by methods that will increase the expression of this particular gene in an individual. For example, supplement sun-creams could be one of the protection methods against skin cancer in the near future.

3676

Speedy Gene Test Leads To ‘Smart Treatments’ For Individual Cancer Patients

New individual speedy gene tests can detect gene abnormalities in cancer patients and can help scientists create and doctors use “smarter treatments” to increase cancer patients life expectancy.

The new test screens for 14 distinct key mutations that are directly linked to cancer. The test is conducted on tumor tissue samples and the results are ready in about three weeks. Depending on the results, patients who had surgery will receive the best treatment option available for their specific mutation.

Researchers from the US informed that the new speedy gene test is now available, and there are already some non-small cell lung cancer patients who benefited from its results.  One from ten screened patients, was found with a certain mutation that would normally not show up in standard tests and could have led to unnecessary treatments or unwanted side effects.

A study recently published in Annals of Oncology journal, suggests that the new test can lead to more specific cancer treatments.

The new gene test was developed by Dr Lecia Sequist and Dora Santagata co-director of the Massachusetts General Hospital Translational Research Laboratory.

Dr Lecia Sequist test is so specific because it helps doctors look for mutations in cancer cells , and not in healthy body cells. These mutations in simple terms give mutant cancer cells the possibility to multiply chaotically and treatments that are specific for each gene mutation have been available for some time now. Knowing the exact mutation can lead to an exact treatment target that is more likely to be effective.

Choosing the correct treatment option can raise the response rate in non-small cell lung cancer from 30% to up to 75% and could significantly improve survival rates according to Dr Lecia Sequist.

DNA mapping1

Genetic Cancer Test

In a recent study which included near 600 lung cancer patients, cancer tissue samples were screen for 50 gene mutation sites from a total of 14 genes. The avreatge time from sample harvesting to result was about 19 days. Fifty per cent of the tested samples were found positive for one or several mutations. Not so long ago, gene testing was posible only for a few mutation at the same time.

Dr Lecia Sequist and Dora Santagata were the first to succeed in screening multiple gene mutations in NSCLC patients using only one specific test. This particular test is a very important step forward for specific targeted cancer therapy. The results concluded that up to 10% of tested patients presented gene mutations that could not be normally found performing less comprehensive tests. The good news is that cancer laboratories already have the necessary equipment that can be used to perform this specific test.

Dr Dias-Santagata is now busy screening other potential beneficiaries for gene abnormalities such as breast cancer patients, cerebral cancer patients and colon cancer patients. Blood cancers and acute myeloid leukaemia are next on the list.

5181

NSAIDs

Anti-inflammatory drugs are a very popular medication class but can be a miscarriage cause according to a new study published online in the Canadian Medical Association Journal.

Common drugs used to handle pain also known as painkillers or NSAIDs can harm the fetus. Usually the drug package leaflet warns pregnant woman to consult a doctor before taking the pills and to avoid NSAIDs in the last trimester of pregnancy. The new study investigated the potential harm of NSAIDs in the first trimester of pregnancy.

Any woman who wants to get pregnant and abandoned contraception, should be more careful when it comes to medication.

NSAIDs

NSAIDs

In Quebec, all anti-inflammatory drugs can be bought using a medical prescription, except ibuprofen – Advil, drug which does not require a medical prescription.

Study leader, Anick Berard looked into the case of 4,7000 women who miscarried, and approximately 47,000 woman who had a normal pregnancy and found out that, during the first five months of pregnancy, about 7,5 %  of women who miscarried used NSAIDS compared to 2,6% of woman who had not miscarried. NSAIDs use was correlated with an 2,5 higher risk of miscarriage. Researchers observed the effects of ibuprofen (Advinl/Motrin), cox-2 inhibitors like colexoxib (Celebrex), diclofenac ( Voltaren, Cataflam, Voltaren-XR), and did not include aspirin in the study or acetamionophen ( Tyenol, Paracetamol) – not an anti-inflammatory drug.

Until now , another two major studies have linked NSAIDs usage and miscarriage. Back in 2001, researchers from Denmark observed a similar risk. In 2003 another study demonstrated that aspirin usage implies a lower risk of miscarriage than ibuprofen and naproxen exposure.

In the U.S, NSAIDs like ibuprofen and naproxen are available over-the-counter, and generally people think that over-the-counter drugs are less dangerous for their health (regarding adverse effects) than drugs available only by prescription.

NSAIDs work by inhibiting 2 enzymes, therefore inhibiting synthesis of prostaglandins (chemicals that mediate the inflammation process and induce fever). The ability to suppress these enzymes along with good marketing make NSAIDs the best-selling drugs on the market. What is not commonly known is that prostaglandins also have a major role in reproduction, and lack of prostaglandins lead to embryo implantation dysfunctions.

During pregnancy it is generally recommended to avoid any anti-inflammatory drugs such as aspirin or ibuprofen. The exact effects of NSAIDs on pregnancy will probably be never known for sure, as it would be unethical to perform a study on pregnant women and potentially harm the development of a fetus.

5004

Incontinence

Urinary incontinence (uncontrollable loss of urine) is a common disease among women. One in three women suffer from urinary incontinence but fortunately there are many effective treatments for this condition. Urinary incontinence is more common in women (especially young women) than men, with a ratio of 5:1. The physiological micturition number is usually 6-9 per day. Obviously, if fluid consumption increased, the micturition number will increase. In women, the number of physiological urination increases with age.

There are two main types of urinary incontinence:

  • Stress incontinence (effort) – due to physical stress such as coughing, sneezing, jumping, lifting weights, etc.
  • Urge incontinence – also called neurologic bladder (a sudden muscle contraction bladder) that causes the sensation to urinate and urinary incontinence or detrusor instability (bladder detrusor is the muscle that stops the flow of urine).

There are other types of incontinence as well but those are rare.

Risk Factors

UTIs usually worsen incontinence. On the other hand, one of the symptoms of urinary infection is incontinence. In this case, incontinence improves after appropriate treatment of the urinary infection. A more difficult clinical situation occurs in older women, as one of five women around the age of 65 years have repeated urinary infections. The question here is whether urinary infections are the cause of incontinence or not. If the incontinence does not get better after treatment of recurrent urinary tract infections (most often asymptomatic in older women) the conclusion is that there is no cause-effect relationship between the urinary infections and incontinence.
Interstitial cystitis can’t be a cause of urinary incontinence. If these coexist in the same woman, they are two completely different diagnoses.

Incontinence

Kegel Exercises

Kegel exercises are very effective in treating urinary incontinence. The most important thing is that they are done correctly and for an extended period of time. The role of these exercises is to reinforce the pelvic muscles. Results are visible after about 2-3 months of practice. The doctor is the one who guides patients on how to execute these exercises correctly. Unfortunately, one in three women use this technique without being guided.

How to perform Kegel exercises correctly?

Experts say that these exercises can be done anywhere, but can be quite difficult for beginners. For this reason, for starters, it is better for woman to lie down with one hand on her abdomen to check abdominal muscle relaxation. The exercise consists of pelvic muscle contractions done in the same way that stops the flow of urine during urination. Contraction cycles should be maintained for 4 seconds, followed by relaxation of muscles for 4 seconds and they should be repeated over a period of 5 minutes. These exercises should not be done during urination because they can cause urinary dysfunctions. After a period of 2-3 months, when the muscles are toned enough, women should use this as an advantage in everyday life. For example, they should contract their pelvic muscles before coughing, lifting heavy objects, or other situations in which would cause them urinary incontinence before they practiced these exercises. If the exercises were practiced for a long enough period and in an appropriate manner, resulting in the toning of the pelvic muscles, urinary incontinence will disappear.

4234

Dehydration

In the early stages of affection it is possible to treat dehydration at home. It is necessary to reduce and replace any fluid losses that might occur.

Treating dehydration

Infants and children up to one year

It is not recommended to postpone fluid replacement until the first symptoms of dehydration occur. Children must be hydrated in order to avoid these problems.

  • If the child is breastfed, often nursing is recommended;
  • If the child is bottle fed, feeding him more often is also recommended;
  • Oral rehydration is attempted if there is a slight dehydration. The amount of fluid needed depends on the child’s weight and the severity of dehydration;
  • If the child has started eating cereal, liquids required can be compensated by grain. The child may also eat mashed potatoes or bananas if the child had already been fed these types of food before.

Children aged between 1 year and 11 years

  • It is necessary for parents to ensure that children consume liquids often;
  • For dehydrated children an oral rehydration with orange juice, tap or bottled water is recommended;
  • Parents should allow children to drink as much water as they consider necessary. They should encourage children to drink plenty of fluids. Children aged between 4 and 10 years should drink at least 8 glasses of liquid a day to cover the amount of lost fluid;
  • Milk and cereal can also help restore the amount of liquid consumed daily by the organism.
Dehydration

Dehydration

Adults and children over the age of 12

If a person suffers from dehydration during light or moderate exercise or after outdoor work, that person should:

  • stop work and rest for a few minutes;
  • leave the sunlight and rest a few minutes in a cool place in the shade;
  • remove any excess of clothes;
  • consider consuming soft drinks such as water, juice or energy drinks to replace fluid lost during exercise. It is recommended to drink 2 liters of cold liquid in the next 2-4 hours. About 10 glasses of water a day is the recommended amount to keep body fluids at a normal level and prevent dehydration;
  • rest and hydrate for the next 24 hours. Although the symptoms may disappear after a few hours, a day and a half is needed to replace lost fluids in the body.

Symptoms to watch for during home treatment

  • Severe dehydration;
  • Nausea and vomiting;
  • Excessive fatigue;
  • Little to no urine.

How to prevent dehydration

The following tips can be helpful in preventing dehydration:

  • Prompt treatment at home in case of diarrhea, vomiting or fever;
  • To prevent dehydration during hot days or during exercise, it is best to consume 8-10 glasses of fluid per day;
  • It’s recommended to consume larger quantities of water during and after exercise;
  • It is not recommended to drink coffee or cola drinks that contain caffeine. They increase dehydration and increase urine excretion;
  • Avoidance of hyper-protein regimes. If a person is on a high protein diet, it should consume at least 8-12 glasses of fluid daily;
  • Alcohol is not recommended, not even beer or wine. It increases dehydration and makes it difficult to make the right decisions;
  • Salt tablets are not recommended. Most people have enough salt in their diet;
  • Stop the exercise in case of dizziness or excessive fatigue;
  • Consider wearing a single line of thin, light-colored clothing for outdoor exercise.

Exercising while wearing latex clothing is highly unrecommended!

3774

Dehydration

Dehydration occurs when the body loses too much fluids. This phenomena occurs when water intake is stopped or when large amounts of water are eliminated from the body through diarrhea, vomiting, sweating or exercise. Decreased water intake can cause muscle cramps and fatigue.

The body normally absorbs fluids from the blood or other tissues of the body. But when the organism is dehydrated, it can no longer assure the fluid needed in order for the blood to keep a constant and normal flow, and thus the patient can go into a state of shock, a condition that can threaten life. Dehydration can occur at any age but is very serious for infants, children and the elderly.

In case you or someone close to you experiences dehydration symptoms, emergency treatment is needed. Immediately calling a rescue team is recommended. Symptoms of dehydration consist in the presence of shock in children and the elderly.

DehydrationDehydration in infants and children

Infants and children are more likely to suffer from dehydration because:

  • Children have a higher percentage of body water.
  • Children have a faster metabolism than adults, so children use more of the body’s water;
  • Children’s kidneys are not as well developed as adult kidneys are, thus the kidneys do not conserve enough water;
  • The immune system that helps fight infections is not fully developed in children, thus increasing the chance of getting a disease that may cause diarrhea and vomiting;
  • Often children do not eat or consume enough liquids when they are sick;
  • Children depend on caregivers to nurture and hydrate them.

Dehydration in the elderly

Seniors are more likely to suffer from dehydration because:

  • They do not drink liquids as they do not feel as thirsty as younger patients;
  • Their kidneys do not work as good as those of younger patients;
  • They do not drink fluids, possibly because of incontinence (the inability to control the bladder);
  • Of physical problems or they are suffering from other diseases that:
    • Don’t allow them to hold a glass of water in their hands;
    • Can cause pain when they’re out of bed or standing up from a chair;
    • Doesn’t allow them go to the toilet.

Infants, children and the elderly should be monitored closely to see the initial symptoms of dehydration, whenever they have any problems that cause diarrhea, vomiting or sweating. Signs of an incipient stage of dehydration are:

  • Dry mouth and sticky saliva;
  • Reduced amount of urine and changed urine color (urine is more concentrated);
  • Distracted and very irritable behavior.

4190

Erectile Dysfunction

Impotence (also known as an erectile dysfunction) is a disease that affects 1 in 10 male patients. Although it is a treatable disease, only 10% of all patients experiencing this problem have requested medical aid. Treating impotence is a very important process that should not be avoided!

What is impotence?

Impotence, also called erectile dysfunction, is the persistent inability to achieve or maintain an erection long enough to have sexual intercourse. The term comes from Latin, where the word impotentia means “lack of power.” Impotence is not the same as the reduction or loss of sexual desire. Impotence refers to the inability to use the penis for intercourse, even if the desire and opportunity are present.

Erectile Dysfunction

Erectile Dysfunction

The only symptom of impotence is the inability to achieve or maintain an erection long enough to have sexual intercourse.

What causes impotence?

The main factors that trigger erectile dysfunction can be either physical or psychological. The cause of impotence among young people is generally a psychological one. The most common psychological causes of erectile dysfunction are stress and anxiety. Other factors, such as marital conflict, depression, or the existence of other sexual orientations may contribute to the onset of the disease as well. When men age, the causes of erectile dysfunction are most likely of organic nature. Disorders responsible for most cases of impotence are diabetes, atherosclerosis, vascular disease (either blocked arteries or obstructed penis valves), spinal cord injuries, multiple sclerosis or hormonal disorders. The use of drugs can also cause the appearance of erectile dysfunction. Most common drugs that are known to cause impotence are antihypertensive drugs and psychoactive antidepressants. Propecia, a drug used to combat hair loss, has also been linked with erectile dysfunction. Several Propecia lawsuits have been filed by victims claiming severe erectile dysfunction as a result of taking the drug. Other factors that trigger erectile dysfunction are smoking and alcohol consumption.

Diagnosing impotence

The diagnosis of impotence can be done by the physician, after performing specific tests. If the physical consultation reveals that the testicles are smaller than normal, the doctor may recommend testing the testosterone serum dosage. Through this test, the doctor can determine whether the erectile dysfunction is caused by a hormonal dysfunction or not. Another diagnostic method is the international index of erectile function: this is a questionnaire with 15 questions that the patient must answer. Based on the patients’ answerss, the pjysician can determine the severity of impotence. In some cases, an ultrasound procedure that measures blood flow to the penis can also be used. Another type of investigation, called angiography, can help detect the presence of a blocked blood vessel in the penis. The angiography is a special X-ray procedure that uses the injection of a contrast substance in order to enhance the image. Neurological tests assess nerve transmission problems in the brain. If the doctor suspects that one of the administered medication could be the cause of impotence, he can replace that particular medication with something similar.

Erectile DysfunctionTreating impotence

The type of treatment recommended will depend on the cause of impotence. There are two options, one being the psychological treatment and the other being medication. Drug treatment based on Sidenafil citrate (better known as Viagra) is one of the most popular. Men whose impotence is caused by hormone deficiencies, may receive synthetic hormones. Synthetic hormones are only prescribed after testing the hormone levels. In general, those who have a history of prostate cancer do not receive hormone injections or pills, because male hormones may increase the cancerous cell growth. In some cases, vascular surgery may be necessary to help increase penile blood flow. If the impotence is caused by some psychological causes, couple therapy can very useful.

mahjong ways viral karena momen menang pemain cara cerdas menang mahjong wins fortune ox bagi bagi scatter
slot online judi bola online judi bola https://widgets-tm.wolterskluwer.com Slot luar negeri no 1 Indonesia adalah slot thailand dengan banyak pilihan provider slot online uang asli, sekali daftar dijamin langsung bisa mainkan semua jenis taruhan online 24 jam. slot thailand jbo680 jbo680 situs slot terpercaya slot pragmatic play online surya168 slot jepang slot online slot gacor catur777 https://slotgacormax.win/ https://wwwl24.mitsubishielectric.co.jp/
slot gacor hari ini
ssh premium
slot
slot thailand
slot gacor
strategi bermain mahjong ways dan pola kemenangan gates of olympus masih jadi favorit banjir scatter hitam bahjong ways
Slot