MALT Lymphoma of the Bladder: A Case Report and Review of the Literature

The presentation of a MALT lymphoma in the bladder is exceedingly rare. Furthermore, the optimal treatment of primary MALT confined to the bladder remains to be defined. Here, we report a case of a 65-year-old female with primary MALT lymphoma treated with definitive radiation therapy. The patient received a total dose of 30 Gy in 20 equal daily fractions to the bladder and tolerated the treatment well. In addition, we have extensively reviewed the relevant literature to better define the optimal management of this rare disease. In conclusion, primary MALT lymphoma of the bladder represents a rare malignancy with excellent prognosis if detected at an early stage. For early stage disease, definitive radiation represents an excellent treatment modality with a minimal side-effect profile

Peroxisome proliferator activator receptor gamma coactivator-1alpha (PGC-1α) improves motor performance and survival in a mouse model of amyotrophic lateral sclerosis

Abstract Background Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease that affects spinal cord and cortical motor neurons. An increasing amount of evidence suggests that mitochondrial dysfunction contributes to motor neuron death in ALS. Peroxisome proliferator-activated receptor gamma co-activator-1α (PGC-1α) is a principal regulator of mitochondrial biogenesis and oxidative metabolism. Results In this study, we examined whether PGC-1α plays a protective role in ALS by using a double transgenic mouse model where PGC-1α is over-expressed in an SOD1 transgenic mouse (TgSOD1-G93A/PGC-1α). Our results indicate that PGC-1α significantly improves motor function and survival of SOD1-G93A mice. The behavioral improvements were accompanied by reduced blood glucose level and by protection of motor neuron loss, restoration of mitochondrial electron transport chain activities and inhibition of stress signaling in the spinal cord. Conclusion Our results demonstrate that PGC-1α plays a beneficial role in a mouse model of ALS, suggesting that PGC-1α may be a potential therapeutic target for ALS therapy.</p

Unintended effects of cardiovascular drugs on the pathogenesis of Alzheimer's disease.

Alzheimer's disease (AD) is rapidly becoming one of the leading causes of disability and mortality in the elderly. As life-expectancy increases, an increasing number of people will rely on modern medicines to treat age-associated disorders. Among these medications, some might benefit, while others might exacerbate, the pathogenesis of AD. We screened 1,600 FDA approved drugs for β-amyloid (Aβ)-modifying activity and identified drugs that can potentially influence amyloid precursor protein processing. In this study, we focused on cardiovascular drugs and demonstrated that some hypertensive medication can differentially modulate Aβ, both in vitro and in vivo. Our study suggests that some commonly prescribed drugs might exert unintended effects and modulate AD and provides the basis for continuing investigation of the role of individual drugs on a case-by-case basis. This line of investigation will lead to the identification of common medications that are potentially beneficial or detrimental to AD as a reference for physicians to consider when prescribing the most appropriate drugs for their patients, particularly for treating chronic disorders among the growing geriatric population

Effect of Caprylic triglyceride on food intake and lifespan of SOD1-G93A animals.

<p>(A) Food intake in SOD1-G93A animals treated with caprylic triglyceride (n = 18) or an isocaloric control diet (n = 17); (B) Mice in the two treatment groups (n = 11) were monitored daily and survival curve was plotted in GraphPad Prism.</p

Mitochondrial bioenergetic profile in the spinal cord of WT and SOD1 G93A mice on control or caprylic triglyceride diet.

<p>Mitochondria were isolated by differential centrifugation from the whole spinal cord of SOD1-G93A mice on control or caprylic triglyceride diet and oxygen consumption rates were analyzed using Seahorse XF24 extracellular flux analyzer. (A) A representative trace of OCR in the presence of pyruvate and malate. Adenosine diphosphate (ADP), oligomycin (O), carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone (FCCP) and a mixture of rotenone, antimycin A, N,N,N’,N’-tetramethylphenylenediamine and ascorbate (RATA) were injected at the indicated time points to measure basal, state 3, state 4o, maximal and complex IV OCR as indicated. OCR in the presence of pyruvate and malate in (B) SOD1-G93A (ALS) and (D) wild type (WT) mice. (C) Spare respiratory capacity of mitochondria from WT and ALS mice on control or caprylic triglyceride diet. Data are mean ± SEM, n = 3 for all groups, *p<0.05 as compared to control by two-tailed student t-test.</p

Glucose tolerance, ketone, triglyceride and corticosterone levels following caprylic triglyceride treatment.

<p>(A) Fasting serum glucose level and (B) glucose tolerance test in SOD1-G93A animals on control or caprylic triglyceride; (C) Blood ketone level at pre-symptomatic (10 weeks) or post-symptomatic (17 weeks) stage; (D) Plasma total triglyceride levels. (E) Plasma corticosterone level. All data are mean ± SEM, n = 4–5 for (A, B), n = 5 for (C) and n = 6–7 for (D, E) *p<0.05 by two-tailed t-test).</p

Nissl-stained motor neuron count in the lumbar spinal cord.

<p>(A) Representative photomicrographs of Nissl-stained sections at the ventral horn area of the lumbar spinal cord; (B) Motor neuron counts. Data are mean ± SEM, n = 3–4 per group, *p<0.05 by two-tailed t-test.</p

Molecular Topology as Novel Strategy for Discovery of Drugs with Aβ Lowering and Anti-Aggregation Dual Activities for Alzheimer’s Disease

<div><p>Background and Purpose</p><p>In this study, we demonstrate the use of Molecular topology (MT) in an Alzheimer’s disease (AD) drug discovery program. MT uses and expands upon the principles governing the molecular connectivity theory of numerically characterizing molecular structures, in the present case, active anti-AD drugs/agents, using topological descriptors to build models. Topological characterization has been shown to embody sufficient molecular information to provide strong correlation to therapeutic efficacy.</p><p>Experimental Approach</p><p>We used MT to include multiple bioactive properties that allows for the identification of multi-functional single agent compounds, in this case, the dual functions of β-amyloid (Aβ) -lowering and anti-oligomerization. Using this technology, we identified and designed novel compounds in chemical classes unrelated to current anti-AD agents that exert dual Aβ lowering and anti-Aβ oligomerization activities in animal models of AD. AD is a multifaceted disease with different pathological features.</p><p>Conclusion and Implications</p><p>Our study, for the first time, demonstrated that MT can provide novel strategy for discovering drugs with Aβ lowering and anti-aggregation dual activities for AD.</p></div