Alkeus to start clincal trials for SD later this year or start of 2013

Another pharmaceutical company dedicated to finding a cure for Stargardt's Disease will start their clinical trials later this year or in 2013. Alkeus research is more focused on a preventive treatment, with an aim of developing compounds to  prevent formation of toxic A2E and lipofuscin pigments, and thus to slow down macular degeneration. Currently, they are finding patients for their clinical trials. You can add yourself to their registry to get future updates on trials.

http://www.alkeus.com/starstudy2.html

Excerpt of a comprehensive article from their website:

"An imperfect recycling system

The retina is the thin membrane located at the back of the eye. It contains millions of photoreceptors used for vision, and plays a similar role as the light sensitive film at the back of a camera. These specialized receptors cover the retina and are responsible for black and white (rods) and for colored vision (cones). Vitamin A, which can be found on the tip of the photoreceptors, is the key molecule to vision. Its exact role was explicited by George Wald and resulted in a Nobel Prize of 1967. In other words, vitamin A is the fuel of vision.

Vitamin A and its derivatives (such as beta-carotene), originate from certain types of food: for example, eggs, milk and other dairy products all contain vitamin A while vegetables, fruits, carrots, etc. contain beta-carotene. After vitamin A is transported into the retina, it is struck by light forcing it to change its molecular shape, and acting like an electrical switch which enables the delivery of an electric signal to the brain. This signals the presence of light to the brain.

After vitamin A has changed its shape, it becomes insensitive to light and needs to be reactivated by specialized cells, the retinal pigmented epithelium (RPE). The geometric switch of vitamin A as well as its recycling by the RPE is called the "visual cycle".

While we would wish vitamin A to be a clean burning fuel, unfortunately, the visual cycle is imperfect and some vitamin A molecules are able to escape the recycling system: these vitamin A can then bind to other vitamin A molecules and create toxic aggregates of vitamin A called vitamin A dimers (or A2E). A2E is then absorbed and stored in the RPE cells where they are considered to be responsible for the formation of other toxic granules named lipofuscin.

With age, accumulation of lipofuscin reduces the proper function of the RPE cells and is thought to be partly responsible for inducing macular degeneration.

Stargardt disease patients present a defective gene which prevents proper transport of vitamin A back into the RPE, which results in even faster formation and accumulation of A2E and lipofuscin. This is why Stargardt disease is also called "juvenile macular degeneration" as the clinical presentations may be somehow similar.

Visual cycle imperfections lead to A2E formation and to macular degeneration. Alkeus Pharmaceuticals is developing compounds that can help perfect this cycle, prevent the formation of toxic A2E and lipofuscin pigments and potentially slow down vision loss in dry-AMD and Stargardt disease."

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Yellow Oleander (Campanilla) Insecticid, reduce and eliminate fever

One of the yellowed flowered, smooth-branched ornamental shrub. Its latex is milky and we use it placing its leaves on our ears like earing  during childhood days. The calyx is green and pointed. The yellow corolla is bell shaped. The fruit is green, smooth and rounded. This can grow up to 7-10 feet in hight and can be seen usually on gardens.

Medicinal use:
Poisoning due to deliberate self-harm with the seeds of yellow oleander (Thevetia peruviana) results in significant morbidity and mortality each year in South Asia. Yellow oleander seeds contain highly toxic cardiac glycosides including thevetins A and B and neriifolin. A wide variety of bradyarrhythmias and tachyarrhythmias occur following ingestion.
Important epidemiological and clinical differences exist between poisoning due to yellow oleander and digoxin; yellow oleander poisoning is commonly seen in younger patients without preexisting illness or comorbidity. Assessment and initial management. Initial assessment and management is similar to other poisonings. No definite criteria are available for risk stratification. Continuous ECG monitoring for at least 24 h is necessary to detect arrhythmias; longer monitoring is appropriate in patients with severe poisoning.
Supportive care. Correction of dehydration with normal saline is necessary, and antiemetics are used to control severe vomiting. Electrolytes. Hypokalemia worsens toxicity due to digitalis glycosides, and hyperkalemia is life-threatening. Both must be corrected. Hyperkalemia is due to extracellular shift of potassium rather than an increase in total body potassium and is best treated with insulin-dextrose infusion. Intravenous calcium increases the risk of cardiac arrhythmias and is not recommended in treating hyperkalemia. Oral or rectal administration of sodium polystyrene sulfonate resin may result in hypokalemia when used together with digoxin-specific antibody fragments. Unlike digoxin toxicity, serum magnesium concentrations are less likely to be affected in yellow oleander poisoning.
The effect of magnesium concentrations on toxicity and outcome is not known. Hypomagnesaemia should be corrected as it can worsen cardiac glycoside toxicity. Gastric decontamination. The place of emesis induction and gastric lavage has not been investigated, although they are used in practice. Gastric decontamination by the use of single dose and multiple doses of activated charcoal has been evaluated in two randomized controlled trials, with contradictory results.
Methodological differences (severity of poisoning in recruited patients, duration of treatment, compliance) between the two trials, together with differences in mortality rates in control groups, have led to much controversy. No firm recommendation for or against the use of multiple doses of activated charcoal can be made at present, and further studies are needed. Single-dose activated charcoal is probably beneficial. Activated charcoal is clearly safe. Arrhythmia management. Bradyarrhythmias are commonly managed with atropine, isoprenaline, and temporary cardiac pacing in severe cases, although without trial evidence of survival benefit, or adequate evaluation of possible risks. Accelerating the heart rate with atropine or beta-adrenergic agents theoretically increases the risk of tachyarrhythmias, and it has been claimed that atropine increases tachyarrhythmic deaths.
Further studies are required. Tachyarrhythmias have a poor prognosis and are more difficult to treat. Lidocaine is the preferred antiarrhythmic; the role of intravenous magnesium is uncertain. Digoxin-specific antibody fragments. Digoxin-specific antibody fragments are effective in reverting life-threatening cardiac arrhythmias; prospective observational studies show a beneficial effect on mortality. High cost and lack of availability limit the widespread use of digoxin-specific antibody fragments in developing countries.

CONCLUSIONS:
Digoxin-specific antibody fragments remain the only proven therapy for yellow oleander poisoning. Further studies are needed to determine the place of activated charcoal, the benefits or risks of atropine and isoprenaline, the place and choice of antiarrhythmics, and the effect of intravenous magnesium in yellow oleander poisoning.

• Insecticide
• To reduce or eliminate fevers
• as a mild laxative

How to use:

• The decoction of the seeds can be uses as insecticide.
• The decoction of the bark of the plant, in moderate doses, is used to reduce and eliminate fever.
• The leaves, is infusion act as a  mild laxative.

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