Depressive sysmtoms linked to therapy uptake

Cognitive Depressive Symptoms and Antiretroviral Therapy Uptake:

Possible Link Between Cognitive Depressive Symptoms, Antiretroviral Therapy Uptake

Possible Link Between Cognitive Depressive Symptoms, Antiretroviral Therapy Uptake

 

The impact of depressive symptoms on antiretroviral therapy are being widely studied , studies have investigated the impact of these symptoms at ART initiation . According to researchers, understanding factors associated with ART initiation may be particularly useful where it is not as commonly prescribed , such as Russia , which has experienced a dramatic increase in rates of HIV infection in the past decade .

Jeffrey Samet, professor of internal medicine and principal investigator of the study, the researchers recruited participants in the evolution of the HIV epidemic in Russia – Mitigating Infection Transmission and Alcoholism in a growing epidemic study . The 133 eligible participants had their severity measured at six and 12 months of brands depressive symptoms.

The results do not provide evidence that the severity of depressive symptoms alone had no statistically significant effect on the initiation of ART , the findings suggest a possible role of cognitive depressive symptoms in decisions to initiate ART. According to investigators, the cognitive symptoms of depression are often regarded as an index of depression that is less influenced by the symptoms of HIV . In addition , the study showed findings consistent with existing studies showing participants with excessive alcohol co – morbid and injection drug use appears to have delayed the start of ART .

” Depressive symptoms have been shown to influence the progression of HIV and have been associated with poor virologic response to treatment and an increased immune failure,” said Tracie Goodness , a doctoral student in clinical psychology at the CAS and corresponding author of the study. “Starting the timely ART has been associated with many positive health effects , such as decreased mortality , increased immune function and lower rates of HIV transmission,” he added.

More research is needed, these results provide initial evidence for the role of depressive symptoms and may contribute to the understanding of the initiation of ART in HIV  infected populations

Link for Colon Cancer Discovered

Key Link Responsible for Colon Cancer Initiation and Metastasis discovered:

Key Link Responsible for Colon Cancer Initiation and Metastasis discovered

Key Link Responsible for Colon Cancer Initiation and Metastasis discovered

CXCR2- a key genetic culprit that is implicated in the tumor formation, growth and progression in a mouse model of colon cancer has been identified by scientists.
 Key Link Responsible for Colon Cancer Initiation and Metastasis discovered

“We have been trying for the past several years to understand the precise molecular links between inflammation and cancer, said DuBois. “We have demonstrated that CXCR2 mediates a critical step in the setup of the blood circulatory machinery that feeds tumor tissue. This provides an important new clue for the development of therapeutic targets to neutralize the effect of CXCR2 on colon cancer.”

The DuBois’ Laboratory for Inflammation and Cancer, which includes lead author Hiroshi Katoh, and colleagues Dingzhi Wang, Takiko Daikoku, Haiyan Sun, and Sudhansu K. Dey, published the results in the November 11 issue of Cancer Cell.

The results provide critical new clues toward the prevention of colorectal cancer, the second leading cause of cancer deaths in the U.S. Despite the availability of colonoscopy screening, the 5-year survival rate remains low, due to a large number patients presenting with advanced stages of the disease. Currently, there are no clinically available blood tests for the early detection of sporadic colon cancer.

Inflammation has long been associated with increasing one’s risk for colon cancer. For instance, more than 20 percent of patients with a form of inflammatory bowel disease (IBD) develop colorectal cancer within 30 years of diagnosis. This colitis-associated cancer has a slow progression, but a very poor response to treatment and a high mortality rate.

Researchers have known that the broad mechanisms of cancer involve an interplay with the immune system response that includes: recruiting immune cells that influence the tumor microenvironment, escaping from host immunosurveillance and suppression, shifting of the host immune response, and tumor-associated angiogenesis to establish the blood supply.

For the study, the research team first “knocked-out” or removed the CXCR2 gene in mice, and found that the signs typically associated with inflammation were prevented. Furthermore, they demonstrated that CXCR2 dramatically suppressed colonic inflammation and the colitis associated tumor formation, growth and progression in mice.

CXCR2 decorates the outer part of immune cells called myeloid-derived suppressor cells, or MDSCs, that work to block the immune response of killer CD8+ T cells. In the knockout mice, without CXCR2 present, the MDSC cells could no longer migrate from the circulatory system to the colon, dodge the killer CD8+ T cell immune response, and feed the blood supply of the tumor environment. Furthermore, when they transplanted normal MDSC cells (with normal CXCR2) into the knockout mice, tumor formation was restored.

“These results provide the first genetic evidence that CXCR2 is required for recruitment of MDSCs into inflamed colonic mucosa and colitis-associated tumors,” said DuBois.

For DuBois, who has devoted his career to unraveling the inflammatory circuitry responsible for colon cancer, the results help connect the dots between the immune system, inflammation and tumor formation and metastasis.

DuBois’ team was the first to show that colorectal tumors contained high levels of the enzyme cyclo-oxygenase-2 (COX-2), a key step in the production of pro-inflammatory mediators such as prostaglandin E2 (PGE2). PGE2 triggers production of a CXCR2 molecule that fits into CXCR2 like a baseball into a glove’s pocket and activates it. CXCR2, like the pied piper, recruits MDSCs from the bloodstream to sites of inflammation, causing the colon cancer tumors to evade the immune killer CD8+ T immune response.

“Our findings reveal not only how MDSCs are recruited to local inflamed tissues and tumor microenvironment and how local MDSCs contribute to colorectal cancer progression, but now also provide a rationale for developing new therapeutic approaches to subvert chronic inflammation- and tumor-induced immunosuppression by using CXCR2 antagonists and neutralizing antibodies,” said DuBois.

Marijuana and Alzheimer’s Disease Pathology

A Molecular Link Between the Active Component of Marijuana and Alzheimer’s Disease Pathology:

A Molecular Link Between the Active Component of Marijuana and Alzheimer's Disease Pathology

A Molecular Link Between the Active Component of Marijuana and Alzheimer’s Disease Pathology

Alzheimer’s disease is the leading cause of dementia among the elderly, and with the ever-increasing size of this population, cases of Alzheimer’s disease are expected to triple over the next 50 years. Consequently, the development of treatments that slow or halt the disease progression have become imperative to both improve the quality of life for patients as well as reduce the health care costs attributable to Alzheimer’s disease.

Since the characterization of the Cannabis sativa-produced cannabinoid, Δ9-tetrahydrocannabinol (THC), in the 1960’s, this natural product has been widely explored as an anti-emetic, anti-convulsive, anti-inflammatory, and analgesic.

The active component of marijuana, Δ9-tetrahydrocannabinol (THC), competitively inhibits the enzyme acetylcholinesterase (AChE) as well as prevents AChE-induced amyloid β-peptide (Aβ) aggregation, the key pathological marker of Alzheimer’s disease. Computational modeling of the THC-AChE interaction revealed that THC binds in the peripheral anionic site of AChE, the critical region involved in amyloidgenesis.

In these contexts, efficacy results from THC binding to the family of cannabinoid receptors found primarily on central and peripheral neurons (CB1) or immune cells (CB2). More recently, a link between the endocannabinoid system and Alzheimer’s disease has been discoveredwhich has provided a new therapeutic target for the treatment of patients suffering from Alzheimer’s disease. New targets for this debilitating disease are critical as Alzheimer’s disease afflicts over 20 million people worldwide, with the number of diagnosed cases continuing to rise at an exponential rate. These studies have demonstrated the ability of cannabinoids to provide neuroprotection against β-amyloid peptide (Aβ) toxicity.Yet, it is important to note that in these reports, cannabinoids serve as signaling molecules which regulate downstream events implicated in Alzheimer’s disease pathology and are not directly implicated as effecting Aβ at a molecular level.

Computational modeling of the THC-AChE interaction revealed that THC binds in the peripheral anionic site of AChE, the critical region involved in amyloidgenesis. Compared to currently approved drugs prescribed for the treatment of Alzheimer’s disease, THC is a considerably superior inhibitor of Aβ aggregation, and this provides a previously unrecognized molecular mechanism through which cannabinoid molecules may directly impact the progression of this debilitating disease.