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EFFECTS OF HIGH RISK PARKINSONS MUTATIONS ARE REVERSIBLE

Researchers from the University of Sheffield have found vital new evidence on how to target and reverse the effects caused by one of the most common genetic causes of Parkinson's.

Mutations in a gene called LRRK2 carry a well-established risk for Parkinson's disease, however the basis for this link is unclear.

The team, led by Parkinson's UK funded researchers Dr Kurt De Vos from the Department of Neuroscience and Dr Alex Whitworth from the Department of Biomedical Sciences, found that certain drugs could fully restore movement problems observed in fruit flies carrying the LRRK2 Roc-COR Parkinson's mutation.

These drugs, deacetylase inhibitors, target the transport system and reverse the defects caused by the faulty LRRK2 within nerve cells. The study is published today (15 October 2014) month in Nature Communications.

Dr De Vos, a Lecturer in Translational Neuroscience at the world-leading Sheffield Institute for Translational Neuroscience (SITraN), said: "Our study provides compelling evidence that there is a direct link between defective transport within nerve cells and movement problems caused by the LRRK2 Parkinson's mutation in flies."

Co-investigator Dr Alex Whitworth explained: "We could also show that these neuronal transport defects caused by the LRRK2 mutation are reversible.

"By targeting the transport system with drugs, we could not only prevent movement problems, but also fully restore movement abilities in fruit flies who already showed impaired movement marked by a significant decrease in both climbing and flight ability."

The LRRK2 gene produces a protein that affects many processes in the cell. It is known to bind to the microtubules, the cells' transport tracks. A defect in this transport system has been suggested to contribute to Parkinson's disease. The researchers have investigated this link and have now found the evidence that certain LRRK2 mutations affect transport in nerve cells which leads to movement problems observed in the fruit fly (Drosophila).

The team then used several approaches to show that preventing the association of the mutant LRRK2 protein with the microtubule transport system rescues the transport defects in nerve cells, as well as the movement deficits in fruit flies.

Dr De Vos added: "We successfully used drugs called deacetylase inhibitors to increase the acetylated form of α-tubulin within microtubules which does not associate with the mutant LRRK2 protein. We found that increasing microtubule acetylation had a direct impact on cellular axonal transport.

"These are very promising results which point to a potential Parkinson's therapy. However, further studies are needed to confirm that this rescue effect also applies in humans."

Dr Beckie Port, Research Communications Officer at Parkinson's UK, which helped to fund the study, said: "This research gives hope that, for people with a particular mutation in their genes, it may one day be possible to intervene and stop the progression of Parkinson's.

"The study has only been carried out in fruit flies, so much more research is needed before we know if these findings could lead to new treatment approaches for people with Parkinson's.

Parkinson's is a degenerative neurological condition, for which there currently is no cure. The main symptoms of the condition are tremor, slowness of movement and rigidity.

HIGH CAFFEINE CAN LOWER EAR RINGING SOUND IN WOMEN

If you are a woman and suffering from ringing or buzzing sound in the ear when there is no outside source of the sounds, increase your tea and coffee intake.

According to new research, women with a higher intake of caffeine had a lower incidence of unexplained ear ringing.

Higher caffeine intake is associated with lower rates of tinnitus in younger and middle-aged women, it added.

The study followed more than 65,000 women. Researchers tracked self-reported results regarding lifestyle and medical history from these women, aged 30 to 44 years and without tinnitus in 1991.

After 18 years of follow up, researchers identified 5,289 cases of reported incident tinnitus.

“We observed a significant inverse association between caffeine intake and the incidence of tinnitus among these women,” said Gary Curhan, a physician-researcher at the Channing Division of Network Medicine at Brigham and Women’s Hospital (BWH) in Boston, Massachusetts.

Significantly, researchers found that when compared with women with caffeine intake less than 150 milligrams/day (one and a half 8-ounce cups of coffee), the incidence of reported tinnitus was 15 percent lower among those women who consumed 450 to 599 mg/day of caffeine.

The majority of caffeine consumed among the women was from coffee and the results did not vary by age.

“We know that caffeine stimulates the central nervous system and previous research has demonstrated that caffeine has a direct effect on the inner ear in both bench science and animal studies,” Curhan noted.

Researchers note that further evidence is needed to make any recommendations about whether the addition of caffeine would improve tinnitus symptoms.

The research appeared in the journal American Journal of Medicine.

HIGH SALT PREVENTS WEIGHT GAIN IN MICE ON A HIGH FAT DIET

In a study that seems to defy conventional dietary wisdom, University of Iowa scientists have found that adding high salt to a high-fat diet actually prevents weight gain in mice.

As exciting as this may sound to fast food lovers, the researchers caution that very high levels of dietary salt are associated with increased risk for cardiovascular disease in humans. Rather than suggest that a high salt diet is suddenly a good thing, the researchers say these findings really point to the profound effect non-caloric dietary nutrients can have on energy balance and weight gain.

"People focus on how much fat or sugar is in the food they eat, but [in our experiments] something that has nothing to do with caloric content -- sodium -- has an even bigger effect on weight gain," say Justin Grobe, PhD, assistant professor of pharmacology at the UI Carver College of Medicine and co-senior author of the study, which was published in the journalScientific Reports on June 11.

The UI team started the study with the hypothesis that fat and salt, both being tasty to humans, would act together to increase food consumption and promote weight gain. They tested the idea by feeding groups of mice different diets: normal chow or high-fat chow with varying levels of salt (0.25 to 4 percent). To their surprise, the mice on the high-fat diet with the lowest salt gained the most weight, about 15 grams over 16 weeks, while animals on the high-fat, highest salt diet had low weight gain that was similar to the chow-fed mice, about 5 grams.

"We found out that our 'french fry' hypothesis was perfectly wrong," says Grobe, who also is a member of the Fraternal Order of Eagles Diabetes Research Center at the UI and a Fellow of the American Heart Association. "The findings also suggest that public health efforts to continue lowering sodium intake may have unexpected and unintended consequences."

To investigate why the high salt prevented weight gain, the researchers examined four key factors that influence energy balance in animals. On the energy input side, they ruled out changes in feeding behavior -- all the mice ate the same amount of calories regardless of the salt content in their diet. On the energy output side, there was no difference in resting metabolism or physical activity between the mice on different diets. In contrast, varying levels of salt had a significant effect on digestive efficiency -- the amount of fat from the diet that is absorbed by the body.

"Our study shows that not all calories are created equal," says Michael Lutter, MD, PhD, co-senior study author and UI assistant professor of psychiatry. "Our findings, in conjunction with other studies, are showing that there is a wide range of dietary efficiency, or absorption of calories, in the populations, and that may contribute to resistance or sensitivity to weight gain."

"This suppression of weight gain with increased sodium was due entirely to a reduced efficiency of the digestive tract to extract calories from the food that was consumed," explains Grobe.

It's possible that this finding explains the well-known digestive ill effects of certain fast foods that are high in both fat and salt, he adds.

Through his research on hypertension, Grobe knew that salt levels affect the activity of an enzyme called renin, which is a component in the renin- angiotensin system, a hormone system commonly targeted clinically to treat various cardiovascular diseases. The new study shows that angiotensin mediates the control of digestive efficiency by dietary sodium.

The clinical usefulness of reducing digestive efficiency for treating obesity has been proven by the drug orlistat, which is sold over-the-counter as Alli. The discovery that modulating the renin-angiotensin system also reduces digestive efficiency may lead to the developments of new anti-obesity treatments.

Lutter, who also is an eating disorders specialist with UI Health Care, notes that another big implication of the findings is that we are just starting to understand complex interactions between nutrients and how they affect calorie absorption, and it is important for scientists investigating the health effects of diet to analyze diets that are more complex than those currently used in animal experiments and more accurately reflect normal eating behavior.

"Most importantly, these findings support continued and nuanced discussions of public policies regarding dietary nutrient recommendations," Grobe adds.

In addition to Grobe and Lutter, the UI research team included Benjamin Weidemann; Susan Voong; Fabiola Morales-Santiago; Michael Kahn; Jonathan Ni; Nicole Littlejohn; Kristin Claflin; Colin Burnett; and Nicole Pearson. The study was funded in part by grants from the National Heart, Lung and Blood Institute, the American Diabetes Association, and American Heart Association.

HOMOEOPATHIC REMEDIES FOR HIGH LEVEL OF CREATININE IN BLOOD

Creatinine  is a chemical waste product that is produced by muscle metabolism and to a small extent by eating meat. Healthy kidneys filter creatinine and other waste products from the blood. The filtered waste products leave the body through urine.Creatinine is produced from creatine. Approximately 2% of the body’s creatine is converted to creatinine every day.

If your kidneys are not functioning properly , an increased level of creatinine may accumulate in your blood. A serum creatinine test measures the level of creatinine in your blood and provides an estimate of how well your kidneys filter.A creatinine urine test can measure creatinine in your urine.

Most men with normal kidney function have approximately 0.6 to 1.2 milligrams/deciliters of creatinine. Women usually have lower creatinine levels than men because women on average have less muscle than men.

Causes--Any condition that impairs the function of the kidneys is likely to raise the creatinine level in the blood. It is important to recognize whether the process leading to kidney dysfunction –kidney failure- is longstanding or recent. Recent elevations may be more easily treated and reversed.

The most common causes of longstanding , chronic kidney disease in adults are—high blood pressure and diabetes.

Other causes of elevated blood creatinine levels are-

·         Certain drugs e.g. cimetidine can sometimes cause abnormally elevated creatinine levels.

·         After ingestion of a large amount of dietary meat

·         Kidney infections, rhabdmyosis, abnormal muscle breakdown and urinary tract infection may also elevate creatinine levels.

Creatinine  test—A creatinine blood test can assess the creatinine levels in blood if you show signs of kidney disease. These symptoms include-

·         Fatigue and trouble sleeping

·         A loss of appetite

·         Swelling in the face , wrists , ankles or abdomen

·         Lower back pain near the kidneys

·         Changes in urine out put and frequency

·         High blood pressure

·         Nausea

·         Vomiting

HOMOEOPATHIC REMEDIES

Well selected Homoeopathic remedies are very effective for controlling creatinine level in blood, and it helps to maintain the normal level safely without any side effects.

CUPRUM ARSENITUM 3x-Cuprum ars is also a very effective remedy for high level of creatinine in blood. There is kidney inefficiency and uremia. The urine smell like garlic. Urine of high specific gravity increased, acetones and diacetic acid.

CUPRUM ACETICUM 3X- In Cuprum aceticum the tongue is pale , coated with lot of mucus. Anemia. Pulse rapid. The patient is chilly. Breathlessness with dry cough. Cannot eat or drink without retching.

SERUM ANGUILLAE 6X—Serum Anguilae is one of the best remedies for high level of creatinine in blood. It is very effective in acute nephritis. Kidney failure. It is prescribed when hypertension and oliguria without oedema is present. Urine contains albumin.

ARALIA HISPIDA 30-Aralia hispida is found to be effective for high level of creatinine in blood. There is dropsy of renal origin. Urinary tract infection is present. Urine is scanty leading to complete suppression of urine. Renal diseases with constipation.

AMPELOPSIS QUINQUEFOLIA 30- Ampelopsis quinquefolia is another effective remedy for high level of creatinine in blood. There is uraemia or uremic coma. Vomiting, purging, tenesmus , cold sweat and collapse are the leading symptoms. 

ARSENICUM ALBUM- 30-Arsenic alb. Is also an effective remedy for high level of creatinine in blood. Urine is scanty, burning when urinating. Albuminuria. Epithelial cells, cylindrical clots of fibrin and globules of pus and blood in urine. Feeling weakness in abdomen after urination.Retention of urine.Urine black as if mixed with dung.

LYCOPODIUM CLAVATUM 30—Lycopodium is an effective remedy for high level of creatinine in blood. Urine scanty , cries before urinating, red sand in urine, must strain, suppressed or retained. Urine milky and turbid. Sometimes haematuria . Urine is burning and hot. The right kidney is mainly affected. The patient experiences impotency.The patient likes warm food and drink, also there is intense craving for sweets.

APIS MELLIFICA 3x- Apis mel is another effective remedy where edematous swellings of face and extremities are present with thirstlessness.. Urination frequent but scanty. There is a feeling of suffocation and breathing difficult. All symptoms are worsen from heat and better from cold.

CANTHARIS 30- Cantharis is best for kidney failure where uremic delusions with sens of persecution is found. There is suppression of urine with restlessness, flushed face and sparkling eyes. The patient has an urge to pass urine but nothing is voided, there being no urine in bladder.

TEREBINTH 30-Terebinth is prescribed where uremia with spasms and lock jaw is present which may be occurring every 15 minutes. There is violent convulsions producing most frightful opisthotonos.

HELLEBORUS NIGER 30- Hellebotus is best for high creatinine in blood with remia and unconsciousness. Pupils dilated and insensible to light. Convulsion is present. The body have a strong urinous odor.

UREA 30—Urea is prescribed where uremia is present. Urine is thin and of low specific gravity.

BELLADONNA 30- Belladonna is used in the acute stage where uremia  occurs in healthy patients when kidney ceases to function and urine becomes dark and turbid. There is twitching of the muscles with violent convulsions.