Habitat :Alnus nitida is native to E. Asia – Himalayas. It grows by rivers and streams, 600 – 1200 metres, occasionally to 2700 metres.
Alnus nitida is a deciduous Tree growing 20 m or more tall. Young shoots pubescent, becoming glabrescent when old. Leaves ovate to elliptic-ovate, 5-15 cm x 3-9 cm, acute or acuminate, remotely serrate to sub-serrate, pubescent to pilose, often villous at the angles of the veins on the under surface, base cuneate to rounded; petiole 1-4 cm long, glabrous to pubescent. Male flowers in catkins, up to 19 cm long; peduncle 5-6.5 mm long; bract c. 1.2 mm long, more or less ovate, bracteoles smaller, suborbiculate. Tepals oblong-obovate to spathulate, c. l mm long, apex and margin minutely toothed. Anthers c. 1 mm long, filament slightly shorter than the tepals, scarcely forked. Female flowers in erect ‘woody cones’, 3-3.5 cm x c. 1.2 cm; bract broadly ovate, bracteoles suborbiculate. Styles 2, linear. Fruiting scale 5-lobed, 5-6 mm long, apex obliquely truncate. Nut 2.5-4 mm long, fringed by the narrow and more or less leathery wings.
It is in flower in September. The flowers are monoecious (individual flowers are either male or female, but both sexes can be found on the same plant) and are pollinated by Wind.It can fix Nitrogen.
Suitable for: medium (loamy) and heavy (clay) soils and can grow in heavy clay and nutritionally poor soils. Suitable pH: acid, neutral and basic (alkaline) soils. It can grow in semi-shade (light woodland) or no shade. It prefers dry moist or wet soil.
Prefers a heavy soil and a damp situation. Grows well in heavy clay soils. Tolerates drier soils than most members of this genus. Succeeds in very infertile sites. Trees probably tolerate temperatures down to between -5 and -10°c and so will not succeed outdoors in the colder areas of the country. A very ornamental tree. This species has a symbiotic relationship with certain soil micro-organisms, these form nodules on the roots of the plants and fix atmospheric nitrogen. Some of this nitrogen is utilized by the growing plant but some can also be used by other plants growing nearby.
Seed – best sown in a cold frame as soon as it is ripe and only just covered. Spring sown seed should also germinate successfully so long as it is not covered. The seed should germinate in the spring as the weather warms up. When large enough to handle, prick the seedlings out into individual pots. If growth is sufficient, it is possible to plant them out into their permanent positions in the summer, otherwise keep them in pots outdoors and plant them out in the spring. If you have sufficient quantity of seed, it can be sown thinly in an outdoor seed bed in the spring. The seedlings can either be planted out into their permanent positions in the autumn/winter, or they can be allowed to grow on in the seed bed for a further season before planting them. Cuttings of mature wood, taken as soon as the leaves fall in autumn, outdoors in sandy soil.
Medicinal Uses: A decoction of the bark is applied externally to treat swellings and body pains.
Other Uses: Tannin is obtained from the bark, it is used in dyeing. Wood – soft, even grained, hard to cut. Used for construction and furniture
Disclaimer : The information presented herein is intended for educational purposes only. Individual results may vary, and before using any supplement, it is always advisable to consult with your own health care provider.
The team observed considerable diversity of bacterial life in the overall salivamicrobiome, both within and between individuals. But when comparing samples from different geographic areas they found not much variation, suggesting that bacteria within the mouth of a person’s neighbor is likely to be just as different as someone on the other side of the world. The findings could help better understand human migrations and populations.
Glucosamine (C6H13NO5) is an amino sugar and a prominent precursor in the biochemical synthesis of glycosylated proteins and lipids. A type of glucosamine forms chitin, which composes the exoskeletons of crustaceans and other arthropods, cell walls in fungi and many higher organisms. Glucosamine is one of the most abundant monosaccharides. It is produced commercially by the hydrolysis of crustacean exoskeletons or, less commonly and more expensive to the consumer, by fermentation of a grain such as corn or wheat. Glucosamine is commonly used as a treatment for osteoarthritis, although its acceptance as a medical therapy varies.
Glucosamine is a compound found naturally in the body, made from glucose and the amino acid glutamine. Glucosamine is needed to produce glycosaminoglycan, a molecule used in the formation and repair of cartilage and other body tissues. Production of glucosamine slows with age.
Glucosamine is available as a nutritional supplement in health food stores and many drug stores. Glucosamine supplements are manufactured in a laboratory from chitin, a substance found in the shells of shrimp, crab, lobster, and other sea creatures. In additional to nutritional supplements, glucosamine is also used in sports drinks and in cosmetics.
Glucosamine is often combined with chondroitin sulfate, a molecule naturally present in cartilage. Chondroitin gives cartilage elasticity and is believed to prevent the destruction of cartilage by enzymes. Glucosamine is sometimes combined with methylsulfonylmethane, or MSM, in nutritional supplements.
Glucosamine was first identified in 1876 by Dr. Georg Ledderhose, but the stereochemistry was not fully defined until 1939 by the work of Walter Haworth. D-Glucosamine is made naturally in the form of glucosamine-6-phosphate, and is the biochemical precursor of all nitrogen-containing sugars. Specifically, glucosamine-6-phosphate is synthesized from fructose-6-phosphate and glutamine as the first step of the hexosamine biosynthesis pathway. The end-product of this pathway is UDP-N-acetylglucosamine (UDP-GlcNAc), which is then used for making glycosaminoglycans, proteoglycans, and glycolipids.
As the formation of glucosamine-6-phosphate is the first step for the synthesis of these products, glucosamine may be important in regulating their production. However, the way that the hexosamine biosynthesis pathway is actually regulated, and whether this could be involved in contributing to human disease, remains unclear.
Oral glucosamine is commonly used for the treatment of osteoarthritis. Since glucosamine is a precursor for glycosaminoglycans, and glycosaminoglycans are a major component of joint cartilage, supplemental glucosamine may help to rebuild cartilage and treat arthritis. Its use as a therapy for osteoarthritis appears safe, but there is conflicting evidence as to its effectiveness. A randomized, double-blind, placebo-controlled trial found glucosamine sulfate is no better than placebo in reducing the symptoms or progression of hip osteoarthritis.
There is promising evidence that glucosamine may reduce pain symptoms of knee osteoarthritis and possibly slow the progression of osteoarthritis. For example, a study published in the journal Archives of Internal Medicine examined people with osteoarthritis over three years. Researchers assessed pain and structural improvements seen on x-ray. They gave 202 people with mild to moderate osteoarthritis 1,500 mg of glucosamine sulfate a day or a placebo.
At the end of the study, researchers found that glucosamine slowed the progression of knee osteoarthritis compared to the placebo. People in the glucosamine group had a significant reduction in pain and stiffness. On x-ray, there was no average change or narrowing of joint spaces in the knees (a sign of deterioration) of the glucosamine group. In contrast, joint spaces of participants taking the placebo narrowed over the three years.
One of the largest studies on glucosamine for osteoarthritis was a 6-month study sponsored by the National Institutes of Health. Called GAIT, the study compared the effectiveness of glucosamine hydrochloride (HCL), chondroitin sulfate, a combination of glucosamine and chondroitin sulfate, the drug celecoxib (Celebrex), or a placebo in people with knee osteoarthritis.
Glucosamine or chondroitin alone or in combination didn’t reduce pain in the overall group, although people in the study with moderate-to-severe knee pain were more likely to respond to glucosamine.
One major drawback of the GAIT Trial was that glucosamine hydrochloride was used rather than the more widely used and researched glucosamine sulfate. A recent analysis of previous studies, including the GAIT Trial, concluded that glucosamine hydrochloride was not effective. The analysis also found that studies on glucosamine sulfate were too different from one another and were not as well-designed as they should be, so they could not properly draw a conclusion. More research is needed.
Still, health care providers often suggest a three month trial of glucosamine and discontinuing it if there is no improvement after three months. A typical dose for osteoarthritis is 1,500 mg of glucosamine sulfate each day.
Other conditions for which glucosamine is used include rheumatoid arthritis, inflammatory bowel disease (Crohn’s disease and ulcerative colitis), chronic venous insufficiency, and skin conditions, although further evidence is needed.
A typical dosage of glucosamine salt is 1,500 mg per day. Glucosamine contains an amino group that is positively charged at physiological pH. The anion included in the salt may vary. Commonly sold forms of glucosamine are glucosamine sulphate and glucosamine hydrochloride. The amount of glucosamine present in 1500 mg of glucosamine salt will depend on which anion is present and whether additional salts are included in the manufacturer’s calculation. Glucosamine is often sold in combination with other supplements such as chondroitin sulfate and methylsulfonylmethane.
Glucosamine is a popular alternative medicine used by consumers for the treatment of osteoarthritis. Glucosamine is also extensively used in veterinary medicine as an unregulated but widely accepted supplement.
Bioavailability and pharmacokinetics:
Two recent studies confirm that glucosamine is bioavailable both systemically and at the site of action (the joint) after oral administration of crystalline glucosamine sulfate in osteoarthritis patients. Steady state glucosamine concentrations in plasma and synovial fluid were correlated and in line with those effective in selected in vitro studies
There have been multiple clinical trials of glucosamine as a medical therapy for osteoarthritis, but results have been conflicting. The evidence both for and against glucosamine’s efficacy has led to debate among physicians about whether to recommend glucosamine treatment to their patients.
Multiple clinical trials in the 1980s and 1990s, all sponsored by the European patent-holder, Rottapharm, demonstrated a benefit for glucosamine. However, these studies were of poor quality due to shortcomings in their methods, including small size, short duration, poor analysis of drop-outs, and unclear procedures for blinding. Rottapharm then sponsored two large (at least 100 patients per group), three-year-long, placebo-controlled clinical trials of the Rottapharm brand of glucosamine sulfate. These studies both demonstrated a clear benefit for glucosamine treatment. There was not only an improvement in symptoms but also an improvement in joint space narrowing on radiographs. This suggested that glucosamine, unlike pain relievers such as NSAIDs, can actually help prevent the destruction of cartilage that is the hallmark of osteoarthritis. On the other hand, several subsequent studies, independent of Rottapharm, but smaller and shorter, did not detect any benefit of glucosamine.
Due to these controversial results, some reviews and meta-analyses have evaluated the efficacy of glucosamine. Richy et al. performed a meta-analysis of randomized clinical trials in 2003 and found efficacy for glucosamine on VAS and WOMAC pain, Lequesne index and VAS mobility and good tolerability.
Recently, a review by Bruyere et al. about glucosamine and chondroitin sulfate for the treatment of knee and hip osteoarthritis concludes that both products act as valuable symptomatic therapies for osteoarthritis disease with some potential structure-modifying effects.
This situation led the National Institutes of Health to fund a large, multicenter clinical trial (the GAIT trial) studying reported pain in osteoarthritis of the knee, comparing groups treated with chondroitin sulfate, glucosamine, and the combination, as well as both placebo and celecoxib. The results of this 6-month trial found that patients taking glucosamine HCl, chondroitin sulfate, or a combination of the two had no statistically significant improvement in their symptoms compared to patients taking a placebo. The group of patients who took celecoxib did have a statistically significant improvement in their symptoms. These results suggest that glucosamine and chondroitin did not effectively relieve pain in the overall group of osteoarthritis patients, but it should be interpreted with caution because most patients presented only mild pain (thus a narrow margin to appraise pain improvement) and because of an unusual response to placebo in the trial (60%). However, exploratory analysis of a subgroup of patients suggested that the supplements taken together (glucosamine and chondroitin sulfate) may be significantly more effective than placebo (79.2% versus 54%; p = 0.002) and a 10% higher than the positive control, in patients with pain classified as moderate to severe (see testing hypotheses suggested by the data).
In an accompanying editorial, Dr. Marc Hochberg also noted that “It is disappointing that the GAIT investigators did not use glucosamine sulfate … since the results would then have provided important information that might have explained in part the heterogeneity in the studies reviewed by Towheed and colleagues” But this concern is not shared by pharmacologists at the PDR who state, “The counter anion of the glucosamine salt (i.e. chloride or sulfate) is unlikely to play any role in the action or pharmacokinetics of glucosamine”. Thus the question of glucosamine’s efficacy will not be resolved without further updates or trials.
In this respect, a 6-month double-blind, multicenter trial has been recently performed to assess the efficacy of glucosamine sulfate 1500 mg once daily compared to placebo and acetaminophen in patients with osteoarthritis of the knee (GUIDE study). The results showed that glucosamine sulfate improved the Lequesne algofunctional index significantly compared to placebo and the positive control. Secondary analyses, including the OARSI responder indices, were also significantly favorable for glucosamine sulfate.
A subsequent meta-analysis of randomized controlled trials, including the NIH trial by Clegg, concluded that hydrochloride is not effective and that there was too much heterogeneity among trials of glucosamine sulfate to draw a conclusion. In response to these conclusions, Dr. J-Y Reginster in an accompanying editorial suggests that the authors failed to apply the principles of a sound systematic review to the meta-analysis, but instead put together different efficacy outcomes and trial designs by mixing 4-week studies with 3-year trials, intramuscular/intraarticular administrations with oral ones, and low-quality small studies reported in the early 1980s with high-quality studies reported in 2007.
However, currently OARSI (OsteoArthritis Research Society International) is recommending glucosamine as the second most effective treatment for moderate cases of osteoarthritis. Likewise, recent European League Against Rheumatism practice guidelines for knee osteoarthritis grants to glucosamine sulfate the highest level of evidence, 1A, and strength of the recommendation, A.
Clinical studies have consistently reported that glucosamine appears safe. Since glucosamine is usually derived from shellfish, those allergic to shellfish may wish to avoid it. However, since glucosamine is derived from the shells of these animals while the allergen is within the flesh of the animals, it is probably safe even for those with shellfish allergy. Alternative sources using fungal fermentation of corn are available. Another concern has been that the extra glucosamine could contribute to diabetes by interfering with the normal regulation of the hexosamine biosynthesis pathway, but several investigations have found no evidence that this occurs. A review conducted by Anderson et al in 2005 summarizes the effects of glucosamine on glucose metabolism in in vitro studies, the effects of oral administration of large doses of glucosamine in animals and the effects of glucosamine supplementation with normal recommended dosages in humans, concluding that glucosamine does not cause glucose intolerance and has no documented effects on glucose metabolism. Other studies conducted in lean or obese subjects concluded that oral glucosamine at standard doses does not cause or significantly worsen insulin resistance or endothelial dysfunction.
The U.S. National Institutes of Health is currently conducting a study of supplemental glucosamine in obese patients, since this population may be particularly sensitive to any effects of glucosamine on insulin resistance.
In the United States, glucosamine is not approved by the Food and Drug Administration for medical use in humans. Since glucosamine is classified as a dietary supplement in the US, safety and formulation are solely the responsibility of the manufacturer; evidence of safety and efficacy is not required as long as it is not advertised as a treatment for a medical condition.
In Europe, glucosamine is approved as a medical drug and is sold in the form of glucosamine sulfate. In this case, evidence of safety and efficacy is required for the medical use of glucosamine and several guidelines have recommended its use as an effective and safe therapy for osteoarthritis. Actually, the Task Force of the European League Against Rheumatism (EULAR) committee recently granted glucosamine sulfate a level of toxicity of 5 in a 0-100 scale, and recent OARSI (OsteoArthritis Research Society International) guidelines for hip and knee osteoarthritis also confirm its excellent safety profile.
Most studies involving humans have found that short-term use of glucosamine is well-tolerated. Side effects may include drowsiness, headache, insomnia, and mild and temporary digestive complaints such as abdominal pain, poor appetite, nausea, heartburn, constipation, diarrhea, and vomiting. In rare human cases, the combination of glucosamine and chondroitin has been linked with temporarily elevated blood pressure and heart rate and palpitations.
Since glucosamine supplements may be made from shellfish, people with allergies to shellfish should avoid glucosamine unless it has been confirmed that it is from a non-shellfish source. The source of glucosamine is not required to be printed on the label, so it may require a phone call to the manufacturer.
There is some evidence suggesting that glucosamine, in doses used to treat osteoarthritis, may worsen blood sugar, insulin, and/or hemoglobin A1c (a test that measures how well blood sugar has been controlled during the previous three months) levels in people with diabetes or insulin resistance.
Theoretically, glucosamine may increase the risk of bleeding. People with bleeding disorders, those taking anti-clotting or anti-platelet medication, such as warfarin, clopidogrel, and Ticlid, or people taking supplements that may increase the risk of bleeding, such as garlic, ginkgo, vitamin E, or red clover, should not take glucosamine unless under the supervision of a healthcare provider.
The safety of glucosamine in pregnant or nursing women isn’t known.
Scientists suggest that schizophrenia may be a result of the evolutionary demand for bigger brain size in humans.
Some people might be paying a price for humanity’s capacity to engage in mathematics, philosophy, science and the arts. A new study of brains and genes suggests that schizophrenia, the chronic debilitating brain disorder that sometimes defies treatment and remains a medical mystery, might be an undesirable by-product of evolution that has given humans unique, highly-evolved brains.
Researchers in China, Germany and the UK have discovered a large overlap across key genetic and molecular processes in the brain that have changed during human evolution and the biological processes observed in schizophrenia.
Philipp Khaitovich at the Max Planck Institute of Evolutionary Anthropology, Leipzig (Germany), and his colleagues have found that the activity levels of several genes that are altered in schizophrenia changed rapidly during evolution. Most of these changes involve genes that play a key role in energy consumption by the brain which happens to be the most energy-demanding organ in the body.
The study is part of an effort to search for the molecular changes that can account for the evolution of human cognitive abilities — intellect, higher thinking and reasoning. Scientists believe the human brain has dramatically evolved over the past five to seven million years since the split from the common ancestor of humans and chimpanzees, humans’ closest living relatives.
But efforts to compare gene activity in brains and pinpoint these molecular mechanisms that might account for the differences between the capabilities of human and chimpanzees haven’t thrown up any dramatic insights into what makes humans, well, humans. Such studies have revealed differences in gene activities, but the ones specifically related to higher thought processes remain unknown.
Khaitovich and his colleagues reasoned that an alternative approach would be to study how genes change in disorders of the brain that affect thought processes. They picked schizophrenia, an illness marked by delusions, hallucinations and disordered thinking which, psychiatrists say, affects about one in 100 people.
The researchers studied post-mortem brains of healthy people and of schizophrenia patients and compared them with chimpanzee and rhesus monkey brains. They also looked for differences in gene activity and levels of brain chemicals.
The analysis revealed that selected genes and chemicals relating to the energy needs of the brain are altered in schizophrenia and, simultaneously, appear to have changed during human evolution.
These results suggest that the brain’s energy use could be a key factor underlying its capacity for higher thought processes, not observed in other species. This is not surprising at all. The human brain is an energy guzzler. Humans spend about 20 per cent of their total energy on the brain, compared to only about 12 per cent by non-human primates and about 2 per cent to 8 per cent by other vertebrates.
And several studies have shown that brain energy use is altered in brain disorders such as schizophrenia. They have revealed deficiencies in blood flow — the source of energy to brain cells — in the region called the prefrontal cortex in patients with schizophrenia, who were asked to perform complex tasks. Post-mortem studies of schizophrenia brains also show depressed activity of energy-related genes.
The findings may lead to new ways of investigating the brain mechanisms that make humans humans, and those that account for schizophrenia, a condition recognised as a distinct disorder by German psychiatrist Emil Kraepilin nearly 120 years ago.
“Our brains are unique among all species in their enormous metabolic (energy) demand,” says Khaitovich. “If we can better explain how our brains sustain such a tremendous metabolic flow, we will have a much better chance to understand how the brain works and why it sometimes breaks.”
But some neuroscientists believe the new findings should be viewed as preliminary, requiring further authentication because disruptions in energy use by brain cells isn’t a problem exclusively associated with schizophrenia. “Problems with energy metabolism also show up in a number of other brain disorders,” says Vijayalakshmi Ravindranath, director of the National Brain Research Institute, Gurgaon.
Khaitovich and his colleagues concede that more research involving a wider range of neuropsychiatric disorders would be necessary. Who knows, there might also be other potential penalties the human brain is forfeiting for all its superior capabilities!
It may have been ascribed a name more than a century ago, but Alzheimer’s disease — the most common form of dementia that makes people forget names, places and things and lose track of time and events irretrievably — still remains a mystery.
Science has so far failed to fully understand the exact cause of this brain disorder, let alone develop a cure. Alzheimer’s strikes at old age, occasional memory lapse being the first symptom. The condition deteriorates rapidly and those suffering from its severest forms may not be able to recognise even their closest family members. Moreover, the patients often experience delusions and hallucinations.
The name “Alzheimer’s disease” entered the medical lexicon in 1907 following a description of the condition by the German physician Dr Alois Alzheimer at a scientific meeting the year before. Dr Alzheimer happened to treat a female patient in 1901 who had some peculiar symptoms: problems with memory, unfounded suspicions about her husband’s fidelity and difficulty in speaking and understanding what was said to her. After her death — which was about five years later — he performed an autopsy on her, of course with her family’s permission. He found that her brain had shrunken dramatically, particularly in the cortex region, the outer layer involved in memory, thinking, judgement and speech.
Scientists may still not know the cause of the disease, but recent advances in neuro-imaging techniques have shown that those suffering from it have two abnormal structures in their brain: plaques formed of deposits of a sticky protein fragment called beta-amyloid, and tangled or twisted fibres of another protein called tau inside the dying nerve cells.
Actually, most people develop plaques and tangles as they age, but those with Alzheimer’s tend to form them on a much larger scale. Ever since the discovery of these unusual elements in the brain of Alzheimer’s patients, scientists have been trying to ascertain their role in triggering as well as in the progression of the disease.
There have been three independent studies recently — two of them involving Indian researchers — that have greatly enhanced scientists’ understanding of Alzheimer’s.
The first, by a team of researchers that included Ganesh Shankar and Tapan Mehta of Harvard Medical School, shows that all the beta-amyloid in an Alzheimer’s patient’s brain is not directly responsible for the disease. The work, led by Dennis Selkoe of the Centre for Neurologic Diseases at Harvard, is the first such study to unlock the cascade of molecular events that lead to this debilitating condition. The team also has researchers from University College, Dublin, and the Royal College of Surgeons in Ireland.
Selkoe and his team observed for the first time that beta-amyloid exists in various forms. While some of these survive as single molecules called monomers, there are others which are formed by two or more molecules of beta-amyloid that stick together and which are soluble. Then there are clumps which are not soluble at all.
The study, recently published in Nature Medicine, came up with an interesting finding. The scientists first isolated beta-amyloid from the brains of Alzheimer’s patients, separating them as monomers, oligomers and insoluble plaque. They then injected these separately into the brains of mice. To their surprise they found that memory was impaired only when soluble beta-amyloid oligomers were administered to the hippocampus (brain region where memory is stored) of the animals.
The exposure to soluble beta-amyloid reduced the density of dendrite spines (that actually receive and transit messages sent by other brain cells) in the hippocampus by almost half. This led the scientists to conclude that soluble beta-amyloid molecules act directly on synapses, the connections between neurons that are necessary for communication in the brain.
When they exposed the mice nerve cells to amyloid plaques from which soluble beta-amyloid had been removed, the researchers found that there was no disturbance in the brain signalling.
“We think that plaques are protective, but it’s the soluble oligomers that interrupt synaptic function,” says Selkoe.
“The study has put yet one more piece into place in the puzzle that is Alzheimer’s,” observes Richard Hodes, director of the US National Institute on Aging that financed the study.
The second study, by Lawrence Rajendran, a post-doctoral student at the Max Planck Institute of Molecular Cell Biology and Genetics at Dresden in Germany, and colleagues looks into the very formation of beta-amyloid. Their work shows that beta-secretase, an enzyme that chops down a molecule called amyloid precursor protein to make beta-amyloid, works only in a tiny compartment inside the brain cell.
Beta-secretase, which is found in the cells of many organs, is an innocent bystander most of the time, Rajendran told KnowHow. “Only when it is inside the endosome — a tiny compartment in brain cells — does it assume a villainous form,” he says. He thinks that if scientists can devise a strategy to attack beta-secretase inside the endosomes, they can control the production of beta-amyloid.
Yet another study by researchers in the UK and Canada, which appeared last week in Nature Cell Biology, says that the best way to treat Alzheimer’s is to trick the brain into not producing the tau protein, which forms the aggregates called tangles. The scientists, who studied the chemistry and structure of the tau protein, designed an enzyme inhibitor which uses a sugar molecule to lower the production of the protein.
With the new insights, scientists hope that the management of Alzheimer’s disease — which is estimated to cost more than $300 billion a year — may become easier. Perhaps there may soon be drugs that can treat the worst of neuro degenerative disorders.