Stem cell therapy for bowel disease

According to an article published in the FASEB Journal, researchers at Wake Forest Baptist Medical Center have discovered a possible treatment for inflammatory bowel disease. A special population of stem cells found in the bone marrow has been identified and it appears that these cells are able to migrate into the gut and restore damaged tissue in IBD.
IBD  refers to a disorder with unknown etiology and with chronic evolution. The term actually refers to ulcerative colitis and Crohn’s disease, which are distinguished by several features. In ulcerative colitis, it is affected the intestinal lining of the rectum, although it can extend virtually to any segment of the digestive tract. Lesions in ulcerative colitis are continuous, unlike Crohn’s disease where lesions are discontinuous and affects the entire intestinal wall. Because the two diseases have similar symptoms, differentiation is made by endoscopy, histopathological examination and clinical and biological investigations. There is however a percentage of 10-15% of the cases in which differentiation between the two forms (Crohn’s disease and ulcerative colitis) cannot be done.

IBD

Statistics show that approximately one million Americans suffer from IBD. Dominant symptoms of the disease are abdominal pain, diarrhea and intestinal bleeding (rectal bleeding, etc.). In addition there are a number of extraintestinal manifestations such as arthritis, uveitis, erythema nodosum. IBD can give a range of gastrointestinal complications (such as perineal fistulas, intestinal obstruction, abscesses, etc.) that require surgical treatment.

Because of the unknown etiology, IBD cannot be cured but there are a variety of drugs that reduce inflammation and frequency of relapses: 5-aminosalicylic agents, systemic corticosteroids (prednisone, etc.), immunosuppressants (azathioprine, cyclosporine, methotrexate, etc.), monoclonal antibodies anti-TNF alpha (infliximab), antibiotics, probiotics, etc.. However, medical treatment is often ineffective. In some cases, IBD has indication for surgery: patients who do not respond to treatment, multiple relapses and complications (such as fistula, occlusion, etc.). Unfortunately, surgery is not curative in all cases because the disease has a high rate of relapse.

The discovery made by the team of researchers led by Graca Almeida-Porada, MD, Ph.D., professor of regenerative medicine at Wake Forest Baptist’s Institute for Regenerative Medicine, completes previous research done last year by Almeida-Porada. He said there have been identified two types of human cells able to migrate into the gut: some responsable for the formation of blood vessels and others that regenerate cells and modulate intestinal inflammation. He also added that in the future they hope to create an injectable treatment for IBD based on the combination of the two types of cells.

Systemic Lupus Erythematosus

As it is an autoimmune disease, systemic lupus erythematosus (SLE)  is characterized by the presence of antinuclear antibodies (ANA) in the blood. They are present in over 95% of patients and are of several types (anti-Smith, anti-double stranded DNA antibodies, anti-histone antibodies and others) and can be detected by several methods: indirect immunofluorescence or ELISA test. Other specific abnormalities found in patients with SLE are hypergammaglobulinemia (IgM and IgG) cryoglobulinemia, low levels of serum complement, elevated rheumatoid factor, etc.
Because the disease is associated with a variety of symptoms (this is why it has been called “the great imitator”), the diagnosis of SLE is based on the criteria proposed by the American College of Rheumatology (ACR). These are:
– Malar rash

– Discoid rash

– Oral ulcers

– Polyserositis (pleurisy, pericarditis)

– Arthritis

– Renal disease

– Neurologic: seizures, psychosis

– Photosensitivity

– Antinuclear antibodies

– Immunological abnormalities: Smith antibodies, antiphospholipid antibodies, etc.

For a patient to be diagnosed with systemic lupus erythematosus is required to meet four of the 11 criteria proposed by the American College of Rheumatology (ACR). It must be said that there are several clinical forms of SLE ( incomplete lupus, drug-induced lupus, antiphospholipid syndrome) and the differential diagnosis is rheumatoid arthritis, Felty syndrome and various kidney, lung, skin and nervous disorders.

Drugs

Treatment

Systemic lupus erythematosus is an incurable disease but it can, however, be kept under control. There are a number of drugs used by patients with systemic lupus erythematosus, depending on the location and severity of disease. Disease-modifying Antirheumatic Drugs (DMARDs) are drugs used to prevent new flares and to reduce the use of corticoisteroids. One of them is hydroxychloroquine (Plaquenil), which is actually an antimalarial, but has been shown to be effective in treating mild forms of lupus. It has few side effects and is well tolerated by patients.

In more severe cases corticosteroids and immunosuppressive agents are needed to alleviate symptoms. There are several  treatment regimens: pulse therapy (methylprednisolone), which is administered intravenously initially and then continued with oral therapy, oral cortisone (prednisone, triamcinolone) etc.. Although effective, corticosteroids give many side effects: weight gain, diabetes, osteoporosis, hypertension etc. Of immunosuppressive agents, there can be mentioned cyclophosphamide, azathioprine, cyclosporine, mycophenolate mofetil, etc.. Patients can use various painkillers (NSAIDs), retinoids or topical glucocorticoids to relieve various symptoms.

Intravenous immunoglobulins can be used in renal disease resistant to other therapies, and  also have the advantage that do not suppress the immune system and therefore there is no risk of infection ( as it is with immunosuppressive drugs). However, in end-stage renal disease renal transplantation remains the only solution. It must be said that, as far as SLE is concerned, there are also other treatments that are under investigation.

Omega-3 fatty acids help prevent skin cancer

A study led by researchers at The University of Manchester reveals that omega-3 fatty acids help prevent skin cancer. This study, conducted by Professor Lesley Rhodes Led, Professor of Experimental Dermatology Center from the Photobiology Unit at the University,  is the first clinical trial that shows the effects of fish oils on skin immunity in healthy volunteers.

Omega-3 fatty acids are polyunsaturated, essential fatty acids, that is they cannot be synthesized by the body. In other words, these fatty acids must be absorbed from the diet for proper functioning of the body. Numerous studies have shown over time that omega 3 and omega 6 have multiple beneficial effects on health: cardiovascular, immune, cancer, cognitive functions. However, some beneficial effects of these compounds are controversial.

But now researchers at The University of Manchester have shown that omega-3 fatty acids, due to immune stimulation, can prevent skin cancer. It seems that these fatty acids combat skin cancer by reducing sunlight-induced immunosuppression. Professor Rhodes, who is based in the Photobiology Unit at the University’s School of Medicine and Salford Royal NHS Foundation Trust, said this is the first study of its kind conducted on humans. She added that it took several years to reach this stage and the results are promising.

omega-3 fatty acid

Patients enrolled voluntarily in this study received a dose of 4 grams of omega-3 fatty acids (equivalent to a portion and a half of oily fish) or placebo daily and were exposed for 8, 15 or 30 minutes at a light solar light using a special machine. Results showed that immunosuppression of those received supplements of omega-3 fatty acids was reduced by 50% compared with those who received placebo. It should be said however that these differences were evident only for exposure of 8 to 15 minutes,  the differences were insignificant for 30 minutes exposure.

These results are important in terms of prevention of skin cancer because it was shown that sunscreens are used inappropriately and only during holidays. In addition, the incidence of skin cancer is on a constant increase in recent decades and the main cause is exposure to sunlight. According to Cancer Research UK, in the UK in 2012 there were approximately 100 000 cases of non-melanoma skin cancer, mostly basal cell carcinomas. Skin cancers are cancers that can be prevented so it is important that people be aware about these protective measures. Professor Rhodes mentioned that omega-3 fatty acids is an extra measure of protection and should not replace sunscreens or physical protection.

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The most common cause of hypercalcemia is endocrine disorder

A study led by UCLA researchers, reveals that the most common cause of increased blood calcium level is primary hyperparathyroidism, that is an endocrine disorder. The study was published in the Journal of Clinical Endocrinology and Metabolism, and is the first of its kind conducted on an ethnically diverse population. Primary hyperparathyroidism is a endocrine disturbance that occurs due to excessive functions of the parathyroid glands, which are endocrine glands located on the thyroid gland. Primary hyperparathyroidism is most often caused by a benign tumor (adenoma), rarely it may be due to hyperplasia of the parathyroid glands and even more rarely can be caused by a cancer developed from these glands. Primary hyperparathyroidism results in hypercalcemia, that is high levels of calcium in the blood, which can affect the bones (it can lead to fractures), kidneys (kidney stones) and other organs. However this disease should be differentiated from secondary hyperparathyroidism which occurs in response to low blood calcium levels.

Thyroid Gland

The researchers found that this disoder, which is manifested by bone loss, fatigue and depression is more common in African-American women aged over 50 years. UCLA researchers found that hyperparathyroidism is the main cause of increased blood calcium level, being responsible for 90% of cases. Dr. Michael W. Yeh, associate professor of surgery and endocrinology at the David Geffen School of Medicine at UCLA, the study’s lead author, said that since the first cause of hypercalcemia is hyperparathyroidism, patients should also check their parathyroid hormone level.

For the study, researchers used a database that included information on 3.5 one million individuals and found that there were 15,234 cases of chronic high-calcium levels. Of these, 87%, that is 13 327 patients, had primary hyperparathyroidism. Yeh said it was surprising that the highest incidence was in black women over 50 years. This category was followed by Caucasians, Asians and Hispanics.  In addition, what was also found was that the incidence of hyperparathyroidism increases with age.

However, Yeh stressed that more studies should be done to see how this disorder evolves in black women because it is known that this population tend to have fewer fractures. This means that they are, to a certain extent, protected against fracture and bone loss. These differences could lead to the development of guidelines based on racial differences. “Women can suffer for years with hyperparathyroidism and not know they have it, which is especially critical in midlife, when bone health is so important,” Yeh points out.

High glycemic index food

According to a study published in The Journal of the Academy of Nutrition and Dietetics, there could be a link between acne and high glycemic index foods. Although this research does not show a causal relationship, it seems that high glycemic index foods can influence and even worsen acne. Based on these data, medical nutrition therapy (MNT) could have an important role in curing or preventing  this skin disease.

Acne is a skin disease that mostly affects teenagers and young adults. There is estimated that 12 million Americans suffer from this disease and although it is not a life-threatening medical condition, acne has many psychological and social implications. Acne may affect quality of life and can lead to anxiety and even depression, so treatment is more than necessary.

High glycemic index food

 Although it is a common condition, especially in adolescents, acne can also affect mature people, that is people over 30-40 years. Acne occurs due to excessive secretion of the sebaceous glands triggered by hormonal disorders. Most often it is caused by an increase in testosterone that occurs during adolescence. But besides testosterone there are also other hormones which are involved, such as dihydrotestosterone (DHT), dehydroepiandrosterone sulfate (DHEAS), cortisol etc.

The link between acne and diet was made since the 1800s, when it was found that this disease occurs mostly in people who consume large amounts of sugar in their diet. Since then chocolate, fat and sugar were considered to play an important role in acne onset. But since 1960 this hypothesis began to be disproved  because two large studies have disputed the link between acne and diet. Jennifer Burris, MS, RD, of the Department of Nutrition, Food Studies, and Public Health, Steinhardt School of Culture, Education, and Human Development, New York University, said this idea that diet does not influence acne was implemented because these two large studies were repeatedly cited in the literature. She also added that dermatologists and dietitians have recently reviewed the relationship between diet and acne and are becoming more interested about the role that medical nutrition therapy may play in the treatment of acne.

To clarify the issue, the researchers conducted a review of studies published between 1960 – 2012 and there was found that  indeed there is a link between acne and high glycemic index / glycemic load diet and frequent dairy consumption. It also found that although there is no strict causal connection, it is possible that diet influence or aggravate acne.

Surveillance may be a better option for older patients with kidney cancer

According to a news release of the American Society of Clinical Oncology (ASCO), ‘watch and wait’ strategy is preferable to surgery in elderly patients with kidney cancer. This alternative seems to be safer than surgery in elderly patients who, because of their  poor health, cannot tolerate general anesthesia and surgery.

The researchers arrived at these conclusions after analyzing approximately 8,000 patients older than 66 years who were diagnosed with small renal tumors, that is tumours with a diameter less than 1.5 inches. It was found that of these patients, 70% had undergone either segmental resection or entire kidney removal, while the other 30% were followed by investigations such as magnetic resonance imaging, computed tomography or ultrasound. “Physicians can comfortably tell an elderly patient, especially a patient that is not healthy enough to tolerate general anesthesia and surgery, that the likelihood of dying of kidney cancer is low and that kidney surgery is unlikely to extend their lives,” said study lead author Dr. William Huang, an assistant professor of urologic oncology at NYU Medical Center.

kidney cancer

What is interesting is that after 5 years of follow-up, 25% of patients died from all causes and only 3% of renal cancer. Moreover, mortality rate of patients who undergone surgery was the same as mortality rate of those unoperated who underwent surveillance. It was also seen that patients who were monitored had a lower rate of death from any cause and a lower risk of having heart problems or stroke. However, Huang mentioned that some patients prefer to be operated. He added that if a patient’s health status allows surgery, he may opt for it because it can prolong life expectancy.

Another finding of researchers at NYU Medical Center was that the number of patients diagnosed with kidney cancer who underwent surveillance increased from 25% to 37% in the period 2000-2007. This shows that doctors began to become aware that small renal tumors, even though cancerous, are not necessarily life-threatening, and that the best option is surveillance. Dr. Manish Vira, director of the fellowship program in urologic oncology at North Shore LIJ’s Arthur Smith Institute for Urology, pointed out that small renal tumors are slowly growing and that the risk is low especially in elderly patients. He also mentioned that although the risk of dying from kidney cancer is small, it is not yet zero, as demonstrated by the 3% of patients who died of kidney tumor. Vira added that an investigation would be interesting to see if these patients have certain risk factors. This would allow researchers to discover specific treatment for elderly patients with small renal tumors.

Australian Researcher Discovered A Way To Turn the HIV Virus Against Itself In Human cells

According to David Harrich, a researcher from the Queensland Institute of Medical Research, in Australia, he has developed a method capable of turning the HIV virus against itself. This is an important breakthrough in future AIDS treatment. The study was recently published in the journal Human Gene Therapy.

Harrich says that the managed to modify a protein that aides the proliferation of HIV, thus turning it into an inhibiting protein. This protein was observed to reduce  the proliferation rate of the HIV virus. Experiments on laboratory animals were thoroughly conducted. Researchers also achieved the same result using Petri dishes. Thorough animal experimentation is needed before human trials can begin. “I have never seen anything like it. The modified protein works every time”, said Harrich. He also added that the new protein, named Nullbasic, inhibited the viral replication by as much as 8 times the normal rate. His research team notes that if research is continued on this current path, a cure for AIDS could be discovered in the near future. However, researcher Frank Wegmann comments that a drug based on this protein is still far from clinical application. According to Wegmann, the creation of such drug would be a great challenge due to the fact that the genetic information would have to be introduced into the genes of patients. This means that all the infected cells should be able to create this new protein. The primary cells infected by the HIV virus are the helper T cells (specifically CD4+ T cells), the macrophages, and the dendritic cells. Wegmann notes that this would require very expensive and potentially dangerous gene therapy.

Currently, researchers from the Australian institute have managed to partly test gene therapy in laboratory conditions, however therapy could have different effects on infected humans. Professor Harrich believes that this new protein, Nullbasic, is a promising step forward in treating AIDS and helping to prevent the spread of the HIV virus. “The virus might infect a cell but it wouldn’t spread. You would still be infected with HIV, but the virus would stay latent, so it wouldn’t develop into AIDS”, noted Harrich. The current promise is that this protein will be able to maintain a healthy immune system. AIDS is defined in terms of either a CD4+ T cell count below 200 cells per µL or the occurrence of any of the 22 specific diseases that are associated with the HIV infection. According to precedent studies and clinical evaluations, if the HIV infection is left untreated, AIDS develops in about 12 years. Current therapy, antiretroviral drugs can only prolong the period that precedes the onset of the disease.

Professor Harrich says that  if the new protein can be introduced as a form of therapy, it could inhibit the viral proliferation for an indefinite period of time. Another beneficial aspect of a new therapy would be the fact that it wouldn’t use multiple drugs, thus offering patients lower costs and a higher life quality. Trials on laboratory animals are planned to start this year.

For more information : study abstract

Study Finds Enzyme Linked to the Acceleration of Malignant Proliferation in CML

A new research led by scientists from the University of California, San Diego School of Medicine, reveals a new enzyme that is thought to play a key role in the process that aides the cloning of malignant stem cells, thus being directly involved in the evolution of CML (Chronic myeloid leukemia). CML is a type of cancer that affects the bone marrow and the blood. Researchers suggest that the prevalence of this type of cancer is increasing.

The paper was published in late December 2012, in the online edition of the journal Proceedings of the National Academy of Sciences. In spite of the recent therapies developed for CML and other leukemias, these diseases still remain a problem because a few cancerous cells avoid destruction and cause a relapse. This process is known as “self-renewal” and it leads to the reappearance of the disease with the possibility of metastasis.

CML

The main author of the study, associate professor Catriona Jamieson, MD, reports that inflammation is responsible for boosting the activity of the ADAR1 (adenosine deaminase) enzyme. Her research team includes researchers from Italy, Canada and from the United States. According to Jamieson, this particular enzyme is expressed early in one’s life and plays a role in the development of blood cells. Afterwards, the enzyme deactivates and is only triggered back on by viral infections. However, the effect of the enzyime in leukemia is that its over-expression amplifies the splicing of RNA, thus leading to a more powerful “self-renewal” process. The current research projects aids precedent studies led by both Jamieson and other researchers. “People normally think about DNA instability in cancer, but in this case, it’s how the RNA is edited by enzymes that really matters in terms of cancer stem cell generation and resistance to conventional therapy.” The described RNA editing process, which occurs in the context of human and other primate specific sequences, also underscores the importance of addressing inflammation as “an essential driver of cancer relapse and therapeutic resistance”, notes Jamieson. She added that the discovery of the enzyme’s role creates the possibility of new future therapies. Jamieson suggests that a future therapy capable of blocking the stem cells in leukemia from using the ADAR1 enzyme could stop the cloning of malignant stem cells. Precedent studies have shown that CML is initiated by a chromosomal abnormality that causes the formation of a mutant gene called BCR-ABL on chromosome 22. CML is usually diagnosed in its late stages due to a dramatic increase of malignant cells. This sudden growth is known as a blast crisis. Most patients are diagnosed around the age of 65. There have been major improvements in CML treatment due to the discovery of tyrosine kinase inhibitor therapies. However, most of the patients will experience a relapse if the therapy is stopped due to the fact that there are several cancer stem cells that are resistant to this therapy.

The current study offers a novel therapy target that could be able to stop the relapse and progression of CML. Approximately 70 thousand people suffer from CML in the United States. This number is predicted to double by the year 2050. Despite the fact that researchers have discovered that the mutant BCR-ABL gene is responsible for the onset of the disease, the cause of the mutation has not yet been identified.

Chronic Myeloid Leukaemia

According to a new report from the National Cancer Intelligence Network (NCIN), the survival of patients with chronic myeloid leukemia increased significantly in recent years compared to the 1990s.

Researchers at The Northern and Yorkshire Cancer Registry and Information Service made a study outlining the duration of survival of patients with different types of blood cancers, based on records of persons who have suffered from cancer between 1995 and 2008. This is the first study of its kind in England and was performed using NCIN Haematology Site Specific Clinical Reference Group (SSCRG).

myeloid leukaemia

Regarding CML, it was observed that the duration of survival has increased dramatically from 41 per cent to 57 per cent among men and from 38 per cent to 59 per cent among women in the period from 1990 to 2000. This is due primarily to the development of new therapies. Tyrosine Kinase inhibitors (TKIs), namely imatinib (Glivec), which was approved in 2001, is the first-line treatment for patients with chronic myeloid leukemia. Dr Robin Ireland, chair of the SSCRG at the NCIN, said it is amazing what difference do new drugs to treat cancer. He added that according to the new report TKIs is a revolutionary treatment for chronic myeloid leukemia. The same optimistic remarks were made by Dr Steven Oliver, Haematological Cancer Epidemiology Lead at NYCRIS and lead author of the report, which said that the duration of survival of these patients has improved considerably. He also said that, due to the development of new-generation TKIs, life expectancy will be even greater.

Chronic myeloid leukemia is a blood cancer that occurs more often in older people. In UK, about 700 cases are diagnosed each year. The causes of this form of leukemia are not fully known although many studies have been made in this regard. It seems that chronic myelogenous leukemia is caused by exposure to ionizing radiation, as many cases were seen in those who were exposed to atomic bombs in Hiroshima and Nagasaki.

Leukemia is a lymphoproliferative disease characterized by the uncontrolled growth of myeloid cells, that is white blood precursor cells. It should be noted that this form of leukemia is associated with a specific translocation called the Philadelphia translocation, that is a switch between two parts of chromosomes 9 and 22. BCR gene on chromosome 22 fuses to ABL gene on chromosome 9. It result in  a tyrosine kinase,  called BCR-ABL , which increases cell division and  inhibits cellular DNA repair, which promotes genomic instability.