FlexPro MD®, a Combination of Krill Oil, Astaxanthin and Hyaluronic Acid, Reduces Pain Behavior and Inhibits Inflammatory Response in Monosodium Iodoacetate-Induced Osteoarthritis in Rats.

Osteoarthritis (OA) is a degenerative joint disease and a leading cause of adult disability. Since there is no cure for OA and no effective treatment to slow its progression, current pharmacologic treatments, such as analgesics and non-steroidal anti-inflammatory drugs (NSAIDs), only alleviate symptoms, such as pain and inflammation, but do not inhibit the disease process. Moreover, chronic intake of these drugs may result in severe adverse effects. For these reasons, patients have turned to the use of various complementary and alternative approaches, including diverse dietary supplements and nutraceuticals, in an effort to improve symptoms and manage or slow disease progression. The present study was conducted to evaluate the anti-osteoarthritic effects of FlexPro MD® (a mixture of krill oil, astaxanthin, and hyaluronic acid; FP-MD) in a rat model of OA induced by monosodium iodoacetate (MIA). FP-MD significantly ameliorated joint pain and decreased the severity of articular cartilage destruction in rats that received oral supplementation for 7 days prior to MIA administration and for 21 days thereafter. Furthermore, FP-MD treatment significantly reduced serum levels of the articular cartilage degeneration biomarkers cartilage oligomeric matrix protein (COMP) and crosslinked C-telopeptide of type II collagen (CTX-II), and the pro-inflammatory cytokines tumor necrosis factor alpha (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6), as well as mRNA expression levels of inflammatory mediators, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), and matrix-degrading enzymes, matrix metalloproteinase (MMP)-2 and MMP-9, in the knee joint tissue. Our findings suggest that FP-MD is a promising dietary supplement for reducing pain, minimizing cartilage damage, and improving functional status in OA, without the disadvantages of previous dietary supplements and medicinal agents, including multiple adverse effects.

The Role of Systemic Therapy in Resectable Gastric and Gastro-oesophageal Junction Cancer.

OPINION STATEMENT: Approximately 20% of patients with cancer of the stomach or gastro-oesophageal junction (GOJ) present with resectable disease. Long-term outcome after surgery alone in these patients is poor, and a combined treatment approach is the standard of care. The two approaches to managing patients with cancer of the GOJ are perioperative chemotherapy or preoperative chemoradiotherapy. Based upon the most recent evidence, patients treated with a perioperative approach and deemed suitable for a triplet regimen should be considered for pre- and post-operative FLOT (5-fluorouracil [5-FU], leucovorin, oxaliplatin and docetaxel) and those suitable for a doublet regimen should be considered for a fluoropyrimidine/platinum combination such as capecitabine and oxaliplatin. Alternatively, such patients may be considered for preoperative chemoradiotherapy according to the CROSS regimen. True gastric cancers may be treated with a perioperative approach or, as is commonly used in Asia, postoperative adjuvant chemotherapy.

Atrioventricular Node Dysfunction and Ion Channel Transcriptome in Pulmonary Hypertension.

BACKGROUND: Heart block is associated with pulmonary hypertension, and the aim of the study was to test the hypothesis that the heart block is the result of a change in the ion channel transcriptome of the atrioventricular (AV) node. METHODS AND RESULTS: The most commonly used animal model of pulmonary hypertension, the monocrotaline-injected rat, was used. The functional consequences of monocrotaline injection were determined by echocardiography, ECG recording, and electrophysiological experiments on the Langendorff-perfused heart and isolated AV node. The ion channel transcriptome was measured by quantitative PCR, and biophysically detailed computer modeling was used to explore the changes observed. After monocrotaline injection, echocardiography revealed the pattern of pulmonary artery blood flow characteristic of pulmonary hypertension and right-sided hypertrophy and failure; the Langendorff-perfused heart and isolated AV node revealed dysfunction of the AV node (eg, 50% incidence of heart block in isolated AV node); and quantitative PCR revealed a widespread downregulation of ion channel and related genes in the AV node (eg, >50% downregulation of Cav1.2/3 and HCN1/2/4 channels). Computer modeling predicted that the changes in the transcriptome if translated into protein and function would result in heart block. CONCLUSIONS: Pulmonary hypertension results in a derangement of the ion channel transcriptome in the AV node, and this is the likely cause of AV node dysfunction in this disease.

Bodily remembering: memory, place, and understanding Latino folk illnesses among the Amuzgos Indians of Oaxaca, Mexico.

This paper takes the theoretical construct of popular nosology of Latino folk illnesses and combines it with Edward Casey's concept of bodily remembering in order to more fully describe the role of memory and place in the illness experiences of the Amuzgos Indians of Oaxaca, Mexico. I ethnographically describe, across time, the interrelated links among social events, physical symptoms, and illness narratives of Latino folk illness popular nosologies as they are contextualized in their unique, social topographies. This enlarged theoretical perspective implies a smallest unit of meaning that is ethnographically defined, but that will often encompass more than the individual sufferer and more than one illness. The research objective of this study was to understand Amuzgan illness experiences through the narratives of detailed case histories and ethnographic observations that were gathered during 18 months of qualitative research. The data show that Amuzgos experience Latino folk illnesses as bodily rememberings of illness events combined with negative interpersonal interactions. Healing these Latino folk illnesses implies curing bodies, households, social relationships, and living environments.

Plasma membrane Ca2+ ATPase 4 is required for sperm motility and male fertility.

Calcium and Ca(2+)-dependent signals play a crucial role in sperm motility and mammalian fertilization, but the molecules and mechanisms underlying these Ca(2+)-dependent pathways are incompletely understood. Here we show that homozygous male mice with a targeted gene deletion of isoform 4 of the plasma membrane calcium/calmodulin-dependent calcium ATPase (PMCA), which is highly enriched in the sperm tail, are infertile due to severely impaired sperm motility. Furthermore, the PMCA inhibitor 5-(and-6)-carboxyeosin diacetate succinimidyl ester reduced sperm motility in wild-type animals, thus mimicking the effects of PMCA4 deficiency on sperm motility and supporting the hypothesis of a pivotal role of the PMCA4 on the regulation of sperm function and intracellular Ca(2+) levels.