Sjogren’s Syndrome

[tirath]

Sjogren’s syndrome is a chronic, slowly progressive, inflammatory autoimmune disorder characterized by the infiltration of specialized cells of the immune system called lymphocytes (T-cells in the majority of cases), monocytes, and plasma cells into the parotid (salivary) glands and lacrimal (tear) glands. These glands are part of a group of exocrine glands whose secretions pass into a system of ducts that lead ultimately to the exterior of the body. This chronic lymphocytic infiltration interferes with the normal function of these glands and eventually results in a significant reduction or cessation in the production and secretion of saliva and tears. The condition is named after Henry Sjogren, a Swedish ophthalmologist, who first described the primary clinical features of this disorder in 1933.

In approximately 40% of patients, Sjogren’s syndrome progresses beyond the exocrine glands and systemic (extraglandular) features develop.

Two distinct forms of Sjogren’s syndrome have been recognized:

Primary Sjogren’s syndrome – defined as dry eye and dry mouth that occurs by itself and is not associated with another autoimmune disorder. Primary Sjogren’s syndrome occurs in approximately 50% of cases according to the Sjogren’s Foundation of America.
Secondary Sjogren’s syndrome – characterized by dry eye and dry mouth that occurs in the presence of a major underlying autoimmune connective tissue disease such as rheumatoid arthritis, systemic lupus erythematosus, or scleroderma.
It has been estimated that up to 4 million Americans are afflicted with Sjogren’s syndrome and that 1-2% of the population in the United States has been diagnosed with Sjogren’s syndrome. However, because the disorder may be difficult to diagnose, the incidence of the disease may be considerably higher. Sjogren’s syndrome is a condition that affects primarily women with a female to male ratio of about 24:1, meaning that about 95% of people who suffer from Sjogren’s syndrome are women. Symptoms of the disorder most often begin between the ages of 40-60, predominantly in peri/post menopausal women, but are also seen in young women in their 20s and 30s. The average age of onset is 52 years old. The overall prevalence of Sjogren’s syndrome in the general population has been estimated to range from 0.5% to 3.0%.

        

[sushantpatel_doc]

Sjögren’s Syndrome Treatment

There is no known cure for Sjögren’s syndrome, nor is there a treatment to restore secretion of moisture by the glands. For the most part, treatment is designed to help relieve symptoms.

If you have Sjögren’s syndrome, several different professionals probably will be involved in your care.

•Your primary-care provider should always be part of your team.

•Rheumatologists have the most specific training and experience in Sjögren’s syndrome as well as the many disorders often associated with the syndrome.

•Ophthalmologists can diagnose early problems with the cornea and assess the degree of damage to the eye. If necessary, they also can perform surgery to help treat or prevent eye damage. They can also help exclude other conditions that cause dry eyes (allergies, contact lens irritation).

•Otolaryngologists (ear, nose, and throat specialists) may be needed if a salivary gland biopsy is necessary to establish a diagnosis. Also, inflammation of the sinuses (sinusitis) occurs more frequently in patients with Sjögren’s syndrome.

•Dentists provide appropriate oral care to prevent and treat tooth decay and gingivitis.

•Other subspecialists may be consulted for specific complications of Sjögren’s syndrome.

        

[Drsumitra]

There is much to suggest that Sjögren’s syndrome (SS) is, like many connective tissue diseases, an autoimmune disorder. Support for this hypothesis includes a female preponderance, distinctive HLA associations, familial clustering with other autoimmune processes, the presence of autoantibodies, and the existence of shared clinical features (arthritis, Raynaud phenomenon, serositis) with other autoimmune connective tissue diseases.

The close relationship of primary SS and systemic lupus erythematosus (SLE) has led to the suggestion that primary SS likely shares common pathogenetic features with SLE [1]. If it is considered that SLE consists of several subgroups that are each characterized by particular autoantibodies and HLA-DR alleles, then SS has close similarities to one of these SLE subsets (ie, HLA-DR3, anti-SS A antibody positive). In this regard, SS might be loosely considered a subset of SLE, characterized by particular homing receptors that allow lymphocytic infiltrates into particular extranodal sites, such as salivary and lacrimal glands. Thus, the features of SS include ocular and oral dryness, as well as increased frequency of lymphoproliferative disorders including an elevated risk of lymphoma [1].

Due to the relative ease and safety of biopsying the target organ of inflammation (eg, the salivary or lacrimal gland, or conjunctiva), SS provides a prototype for understanding the interaction of immune and neuro-endocrine systems. With availability of techniques of molecular biology to analyze the plethora of proteins (proteomics) of small tissue samples and fluids, it should be possible to correlate the changes in tissue with those in blood and draining fluids (ie, tears and saliva) in order to assess prognosis and to provide biomarkers for response to therapy.

Studies have suggested an important role for B-cells and type I interferon [2-6], in contrast to the pivotal role of TNF in RA patients [7-9]. These observations will drive the next stage of therapeutic trials in SS.

Although features of dry eyes, dry mouth and systemic manifestations such as vasculitis remain well understood, the vague symptoms of muscle pain, mild cognitive defects and fatigue (fibromyalgia-like) remain poorly characterized at a molecular level, and treatment for these common symptoms will depend on further understanding of pathogenesis.

 

 

        

[Drsumitra]

Sjögren’s syndrome is thought to be caused by the body’s own immune system. Lymphocytes are a type of white blood cell in the body’s immune system that normally help to protect the body from infection. In Sjögren’s syndrome, these cells are thought to damage the glands that produce tears and saliva.

A person who develops Sjögren’s probably inherits the risk from one or both parents and is then exposed to some type of environmental trigger (eg, a viral infection), but the exact cause in not known. 

SJÖGREN’S SYNDROME SYMPTOMS

The classic symptoms of Sjögren’s syndrome are dry mouth (due to decreased production of saliva) and dry eyes (due to decreased production of tears). Symptoms of SS can develop in otherwise healthy people, especially older adults.

SJÖGREN’S SYNDROME DIAGNOSIS

The most prominent symptoms of Sjögren’s syndrome (eye and mouth dryness) are common and can be caused by conditions other than Sjögren’s syndrome. Therefore, it is important to identify medications or conditions that cause dryness and determine if alternate non-drying treatments are available.

The definition of Sjögren’s syndrome requires that the person have symptoms for a prolonged time (eg, dry mouth for greater than three months) as well as positive laboratory tests. 

Blood tests — A number of blood tests are typically done in people suspected of having Sjögren’s syndrome. One of the most important is a test for the presence of certain antibodies that are markers for autoimmune disorders. ".)

Salivary gland testing — A salivary gland biopsy may be recommended to aid in the diagnosis of Sjögren’s syndrome. The biopsy is done by removing a small piece of tissue from the inner portion of the lip. Other salivary gland tests may also be recommended.

Eye tests — Tests are usually recommended to determine if you produce a normal amount of tears and to determine if there are areas of the eye that have been damaged as a result of dryness. An eye specialist (ophthalmologist) or rheumatologist may perform these tests.

Schirmer test — In the Schirmer test, a small piece of sterile filter paper is inserted gently between the eye and eyelid in the inner corner of the eye. It is removed after several minutes, and the wetness on the paper is then measured. A decreased amount of wetting is characteristic of Sjögren’s syndrome, although decreased tear production can also occur with other conditions.
Rose Bengal test — The dry eye of Sjögren’s syndrome can show damage to the membranes surrounding the eye and eyelids. A test called the Rose Bengal test can detect scratches on the surface of the eye.
SJÖGREN’S SYNDROME COMPLICATIONS

The decreased fluid production in the eyes and mouth can lead to additional problems.

Damage to the surface of the eye can occur when the eyes lack the natural lubricating layer.
Injury to the normally transparent cornea can interfere with vision and cause eye pain.
People with decreased saliva production are at risk of developing cavities in the teeth and infections in the mouth, including painful fungal infections (a yeast infection or thrush).
People with Sjögren’s syndrome have a higher risk of developing diseases of the chest (called interstitial pneumonitis), the kidneys (interstitial nephritis), and thyroid gland abnormalities.
Sjögren’s also increases the risk of a cancer of the lymphatic system (such as non-Hodgkin lymphoma). The lymphatic system includes the tissues and organs that produce and store cells that fight infection, including the bone marrow, spleen, thymus, and lymph nodes

 

        

[Drsumitra]

Amylases find use in breadmaking and to break down complex sugars, such as starch (found in flour), into simple sugars. Yeast then feeds on these simple sugars and converts it into the waste products of alcohol and CO2. This imparts flavour and causes the bread to rise. While amylases are found naturally in yeast cells, it takes time for the yeast to produce enough of these enzymes to break down significant quantities of starch in the bread. This is the reason for long fermented doughs such as sour dough. Modern breadmaking techniques have included amylases (often in the form of malted barley) into bread improver, thereby making the process faster and more practical for commercial use.[6]
Alpha and beta amylases are important in brewing beer and liquor made from sugars derived from starch. In fermentation, yeast ingest sugars and excrete alcohol. In beer and some liquors, the sugars present at the beginning of fermentation have been produced by "mashing" grains or other starch sources (such as potatoes). In traditional beer brewing, malted barley is mixed with hot water to create a "mash," which is held at a given temperature to allow the amylases in the malted grain to convert the barley’s starch into sugars. Different temperatures optimize the activity of alpha or beta amylase, resulting in different mixtures of fermentable and unfermentable sugars. In selecting mash temperature and grain-to-water ratio, a brewer can change the alcohol content, mouthfeel, aroma, and flavor of the finished beer.
In some historic methods of producing alcoholic beverages, the conversion of starch to sugar starts with the brewer chewing grain to mix it with saliva. This practice is no longer in general use.
When used as a food additive, amylase has E number E1100, and may be derived from swine pancreas or mould mushroom.
Bacilliary amylase is also used in clothing and dishwasher detergents to dissolve starches from fabrics and dishes.
Factory workers who work with amylase for any of the above uses are at increased risk of occupational asthma. Five to 9% of bakers have a positive skin test, and a fourth to a third of bakers with breathing problems are hypersensitive to amylase.[7]
An inhibitor of alpha-amylase, called phaseolamin, has been tested as a potential diet aid.[8]
Blood serum amylase may be measured for purposes of medical diagnosis. A normal concentration is in the range 21-101 U/L. A higher than normal concentration may reflect one of several medical conditions, including acute inflammation of the pancreas (concurrently with the more specific lipase),[9] but also perforated peptic ulcer, torsion of an ovarian cyst, strangulation ileus, macroamylasemia and mumps. Amylase may be measured in other body fluids, including urine and peritoneal fluid.
In molecular biology, the presence of amylase can serve as an additional method of selecting for successful integration of a reporter construct in addition to antibiotic resistance. As reporter genes are flanked by homologous regions of the structural gene for amylase, successful integration will disrupt the amylase gene and prevent starch degradation, which is easily detectable through iodine staining.Carbohydrates are an energy rich food source. Amylase is thought to have played a key role in human evolution in allowing humans an alternative to fruit and protein. A duplication of the pancreatic amylase gene developed independently in humans and rodents, further suggesting its importance. The salivary amylase levels found in the human lineage are six to eight times higher in humans than in chimpanzees, which are mostly fruit eaters and ingest little starch relative to humans

 

        

[drmithila]

Studying the mouth, including the diagnostic potential of saliva, is offering opportunities to explore overall health.
In 2010, Michael Lau received an e-mail from a recruiter seeking candidates for a position at the University of California, Los Angeles (UCLA). Would he be interested, the recruiter asked, in applying for a postdoc related to salivary diagnostics? Lau, who was finishing his biochemistry and molecular biology PhD at the University of California, Riverside, and considering his career options, was intrigued and surprised. “I had no idea that you could actually detect systemic diseases, and oral diseases, using saliva,” says Lau.

The opening was in the laboratory of David Wong, associate dean of research at the UCLA School of Dentistry. Wong’s group had found in saliva potential biomarkers for oral cancer and the autoimmune disease Sjögren’s syndrome, and was searching for others. With his interest piqued, and keen on the potential for practical diagnostic use, Lau successfully applied for the post.

Lau investigates how tumours in different parts of the body might affect the contents of saliva. In March, he co-authored a paper suggesting that tiny vesicles from breast-cancer cells can affect the protein and RNA contents of vesicles released by salivary-gland cells (C. S. Lau and D. T. W. Wong PLoS ONE 7, e33037; 2012), and researching the possible mechanisms in a mouse model. Working in this field has offered Lau ample opportunities to break ground. At a time when most scientists are focused on other bodily fluids, such as blood and urine, this is “an untapped field,” he says.

Many people assume that dental research is limited to teeth and gums. But dental researchers have long considered the mouth to be an indicator of conditions elsewhere in the body. Saliva contains many of the same molecules found in blood, albeit often at much lower levels, and might offer a non-invasive way to test for diseases in a dentist’s office, in the field or even at home. Researchers have also uncovered possible links between gum disease and disorders such as diabetes and cardiovascular disease, creating the potential for research into whether improving oral health could help in the prevention or management of these conditions.

Non-invasive diagnosis
Resources for scientists interested in the connections between oral and systemic health have grown over the past decade. The National Institute of Dental and Craniofacial Research (NIDCR) in Bethesda, Maryland, invested US$65.6 million into salivary diagnostics research between 2002 and 2011, and the human salivary proteome — an inventory of proteins secreted by salivary glands — was published in 2008 (P. Denny et al. J. Proteome Res. 7, 1994–2006; 2008). The UK Biobank, a project to build a repository of health and lifestyle data and samples from half a million people, has collected about 130,000 saliva samples, and began accepting research proposals from the international scientific community in March. The Human Microbiome Project supported by the US National Institutes of Health (NIH) has sequenced the genomes of about 130 oral bacteria species. And in 2008, a collaboration between researchers in the United States and the United Kingdom launched the Human Oral Microbiome Database (HOMD), which currently contains the genome sequences of about 270 types of microbes that have been found — some of them only occasionally or during infection — in the oral cavity.

" I had no idea that you could actually detect systemic diseases, and oral diseases, using saliva. "
If a scientist were choosing a bodily fluid to investigate for disease biomarkers a decade ago, saliva wouldn’t have made that list, says Wong. But technological advances and improved lab protocols have allowed researchers to conduct large-scale biomarker screens and detect, with more consistency, low concentrations of molecules such as proteins and RNA in saliva. Although job candidates may be cautious — some sceptics question how saliva could reflect systemic disease — other researchers say that now is a great time to enter this fledgling field. “You’ll be a big fish in a small pond,” says Daniel Malamud, who specializes in oral diagnosis of infectious diseases and is the director of the HIV/AIDS Research Program at New York University College of Dentistry.

Tests on oral fluids already exist for hormones, illegal drugs and HIV. But the funding from the NIDCR over the past decade has kick-started the field, and teams are now investigating the use of salivary biomarkers for conditions ranging from Alzheimer’s disease to heart attacks.
Researchers who work in salivary diagnostics are scattered across dental, medical, biology and engineering departments. PhD graduates in molecular biology, biochemistry, developmental biology and genetics are valued; and statisticians and bioinformaticians are also needed to distinguish significant biomarkers from noise in studies of tens of thousands of genes or proteins. Aims in basic research and device-development often entail technological tasks suited to biomedical engineers, who might develop assays for target molecules, and microfluidics experts, who work out how saliva will flow through a given device. People with experience in electrochemistry, nanotechnology, microfabrication and polymer science also have a role. For example, Fang Wei, a biosensor researcher at the UCLA School of Dentistry, is developing a platform for monitoring the contents of vesicles in saliva in real time. Dental training isn’t necessary. Many of Wong’s postdoctoral fellows have no dentistry skills at all when they first arrive at the lab, but pick up what they need on the job. Lau taught himself salivary biology, and was helped by lab members who did have dental training.

Investigators should consider a wide range of agencies for funding options. The NIDCR is interested in salivary biomarkers for oral or head and neck cancers, and mechanisms to explain how an organ elsewhere in the body can affect the composition of saliva, says Penny Wung Burgoon, director of the NIDCR’s salivary biology and immunology programme. But US researchers interested in systemic disease might have better luck seeking funding at the individual NIH institute that oversees their disease of interest. And last year, the US Defense Advanced Research Projects Agency (DARPA) in Arlington, Virginia, called for research proposals for diagnostic tests that can be easily used in the field to provide on-demand care, such as bioterror-pathogen testing for soldiers. Interest in salivary diagnostic research in Europe lags behind that in the United States, but investigators could apply for grants from funding bodies that cover specific diseases, says Gordon Proctor, a salivary biologist at King’s College London Dental Institute.

Companies designing and developing tests value biochemists, immunologists or those with skills in molecular testing, says Stephen Lee, executive vice-president and chief science officer at OraSure Technologies in Bethlehem, Pennsylvania. Ronald McGlennen, medical director of OralDNA Labs in Brentwood, Tennessee, expects opportunities to arise for medical technologists — who would typically have a bachelor’s degree in medical technology or have completed a relevant training programme — to refine protocols for handling and processing saliva samples. But jobs in this area may be limited because big pharmaceutical and diagnostic companies are waiting for further evidence that tests using saliva are comparable with those that use blood, and that they can meet regulatory standards, says Paul Slowey, chief executive of Oasis Diagnostics in Vancouver, Washington. “A lot of people are sitting on the fence,” he says.

In addition to salivary diagnostics, scientists are investigating associations between gum disease and systemic disorders, raising questions about whether improving oral health could help in the prevention of these conditions. Researchers have long known that frequent gum abscesses can be an indicator of diabetes, and it has been suggested that there may be an association between a healthy mouth and improved control of diabetes. A link between poor oral health and cardiovascular disease and with pregnancy complications has also been suggested, but there is no clear evidence of whether gum disease actually contributes to these disorders.

Investigators seeking to establish associations with diseases need to avoid turning projects into fishing expeditions. “You can make a link with ingrown toenails if you want to,” says Mark Bartold, director of the Colgate Australian Clinical Dental Research Centre at the University of Adelaide. Researchers need first to consider plausible reasons that a mouth infection or inflammation might affect another disease, he says.

Microbiologists, molecular geneticists and medical researchers could apply their expertise to this area. Researchers have found the DNA of oral bacteria in plaques that build up in blood vessels and in the synovial fluid of joints, raising the possibility that these microbes or their products may help to trigger heart attacks, stroke or prosthetic joint failure. Researchers at the Forsyth Institute in Cambridge, Massachusetts, plan to sequence another 100–200 microbe genomes in the next eight years. With genome data and good research tools, scientists can make connections between oral bacteria and disease more rapidly, says Floyd Dewhirst, an oral microbiologist at the Institute. Researchers can explore how these microbes interact with each other and with humans, including how they might affect systemic diseases.

Dental potential
Yet Dwayne Lunsford, director of the NIDCR’s microbiology programme, warns that because links between oral bacteria and systemic disease are still controversial, early-career investigators should be cautious. If peer-review groups are sceptical, they may score a grant application poorly, he says.

Although some research into salivary diagnostics and the links between oral health and systemic disease takes place in medical schools or conventional biology or engineering departments, biologists should not disregard dental-school faculty positions as a possible career destination. For example, the UCLA School of Dentistry has hired a proteomics researcher to work specifically in salivary diagnostics.

Many dental schools are looking for basic-research scientists, says Chris Overall, a proteomics researcher at the University of British Columbia Faculty of Dentistry in Vancouver, Canada. These institutions can give researchers access to patients, providing them with a better understanding of clinically relevant questions.

Researchers who apply for dental faculty positions may find job more easily than those who aim for basic biology departments. “It’s challenging for dental institutions to find people of the calibre that we’re looking for,” says Laurie McCauley, a dentist and bone biologist at the University of Michigan School of Dentistry in Ann Arbor. For applicants with a track record in fields relevant to dentistry, McCauley calls dental faculty positions “a candidate’s market”.

 

        

[drmithila]

Heavy cellphone use increases the rate of saliva and flow, as well as the volume of parotid glands, according to a study
Researchers from the department of oral medicine and radiology at Vidya Shikshan Prasarak Mandal’s Dental College and Research Centre in India were interested in looking at how heat and radiofrequency radiation that cellphones emit can impact adjacent tissues.

"Mobile phones are known to generate heat and emit radiofrequency radiation in the form of nonionizing electromagnetic radiations in the range of 800-2,200 MHz, similar to many home appliances," they wrote. "But the long duration and proximity of mobile phones to human body during use has given rise to concerns of possible adverse effects resulting from absorption of these emissions by the tissues adjacent to the area of mobile phone handset use."

Because the parotid glands are located in front of the ear in close proximity to where cellphones are held when in use, these glands in particular could be vulnerable to adverse effects, the study authors noted.

Previous studies have had considerable variation in their conclusions, suggesting or denying a correlation between heavy cellphone use and headaches, migraines, brain tumors, auditory canal pathologies, and physiologic changes in the salivary glands, they noted.

Dominant vs. nondominant

For this study, the researchers recruited 142 healthy men and women between the ages of 18 and 30 who had used mobile phones for three or more years. The participants had no oral complaints, disorders, or medication use that could affect salivation, nor did they have a history of systemic disorders affecting the head, neck, or face.

Group I, the heavy-user group, consisted of 50 men and 50 women who used their phones for more than two hours per day on average. Group II, which served as the control, comprised 20 men and 22 women who used their phones for less than two hours per day. None of the study participants used a hands-free device.

One week prior to the study, the participants were asked to log their typical cellphone usage habits. They were also tested for salivary flow rate using a modified Schirmer’s test between 9 a.m. and 1 p.m. after being instructed not to eat or drink anything but water for two hours prior to the test. The researchers wanted to test the parotid glands in their resting state, so they asked participants to relax for five minutes before gathering salivary flow rate data.

They compared the saliva flow for both the dominant and nondominant sides of all study participants; the side of the participants’ head where he or she typically held the phone was considered the dominant side in both groups.

For individuals showing an increase of 1.5 mL/5 min or greater in salivary flow rate of the dominant side compared with the nondominant side, the modified Schirmer’s test was repeated on two consecutive days and the average score recorded, the researchers wrote.

Additional tests

The researchers also performed ultrasonography of the superior lobe of the parotid bilaterally in the subjects who displayed greater salivary flow on the dominant side. The superior lobe was chosen due to its anatomic location relative to where cellphones are held when in use.

Next, they completed a statistical analysis of the data, with a p-value of 0.05 or less considered statistically significant. They found that the heavy-user group had a higher rate of salivation on the dominant side at 4.35 ± 3.03 mm/5 min versus 3.4 ± 1.64 mm/5 min on the nondominant side. The dominant side of the control group averaged 3.1 ± 0.3 mm/5 min while the nondominant side was 2.85 ± 0.29 mm/5 min.

"Group I showed 26% more parotid salivation on the dominant side compared with the nondominant side (p < 0.00001)," the researchers wrote. "In contrast, group II showed 8% more salivary flow rate on the dominant side than on the nondominant side (p = 0.562)."

The researchers also observed 13% more average volume of the superior lobe of parotid on the dominant side versus the nondominant side; the difference was only 6% between the dominant and nondominant sides of the control group.

From the present study, "functional and volumetric changes induced in parotid glands are associated with excessive mobile phone use," the researchers concluded.

Interestingly, 30% of the participants reported other problems experienced after cellphone use: 35 reported ringing and heating of the ear and skin, 7 reported headaches, and 5 said they suffered from migraines.

In addition, a failed attempt to measure salivary flow velocity with color Doppler imaging "allowed us to discover that the velocity of blood flow of the external carotid artery within the parotid gland of the dominant side was more than that of the other side, by almost 1.5-fold, in 20 of 38 USG [ultrasound] participants," the researchers wrote. Both Global System for Mobile Communications (GSM) users (68%) and Code Division Multiple Access (CDMA) users (32%) showed increases in salivary flow rate and volume of parotid gland, they noted.

Radiofrequency radiation and heat generated by the phones are possible causes for changes in their users, according to the study authors. Other studies have found that radiofrequency radiation from phones can have an effect.

"Longer use of mobiles can potentially raise skin temperature and increase perfusion of the tissue to reduce the raised temperatures," the researchers wrote.

 

        

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