Effects of low carbohydrate diets high in red meats or poultry, fish and shellfish on plasma lipids and weight loss

<p>Abstract</p> <p>Background</p> <p>Low carbohydrate diets (LCDs) have been demonstrated to be effective tools for promoting weight loss and an improved plasma lipid profile. Such diets are often associated with increased meat consumption, either poultry, fish, and shellfish (PFS), which are generally high in polyunsaturated fat (PUFA) or red meats (RM), generally high in saturated fat (SFA). The fatty acid profile and content of a diet may influence the plasma lipid profile of humans. This study examined whether the type of meat consumed could influence the outcome of an LCD.</p> <p>Methods</p> <p>Moderately obese subjects consumed two different LCDs as part of a weight loss regimen: 1) a diet high in foods of mammalian origin (RM) intended to contain more SFA, or 2) a diet high in PFS intended to contain more PUFA. Diet dependent changes in body weight, nutritional intake, and plasma lipids were evaluated during a 28 day study period.</p> <p>Results</p> <p>Both diets were associated with significant weight loss after 28 days, -5.26 ± 0.84 kg and -5.74 ± 0.63 kg for RM and PFS groups, respectively. The PFS diet was associated with a significantly higher intake of PUFA and cholesterol. Despite high cholesterol and fat intakes, neither diet was associated with significant changes in plasma cholesterol or the plasma lipoprotein cholesterol profile. While plasma triglycerides were reduced in both groups, the effect was only statistically significant for the PFS diet.</p

Ruthenium Complexes are pH-Activated Metallo Prodrugs (pHAMPs) with Light-Triggered Selective Toxicity Toward Cancer Cells

Metallo prodrugs that take advantage of the inherent acidity surrounding cancer cells have yet to be developed. We report a new class of pH-activated metallo prodrugs (pHAMPs) that are activated by light- and pH-triggered ligand dissociation. These ruthenium complexes take advantage of a key characteristic of cancer cells and hypoxic solid tumors (acidity) that can be exploited to lessen the side effects of chemotherapy. Five ruthenium complexes of the type [(N,N)₂Ru­(PL)]²⁺ were synthesized, fully characterized, and tested for cytotoxicity in cell culture (<b>1</b>_<b>A</b>: N,N = 2,2′-bipyridine (bipy) and PL, the photolabile ligand, = 6,6′-dihydroxybipyridine (6,6′-dhbp); <b>2</b>_<b>A</b>: N,N = 1,10-phenanthroline (phen) and PL = 6,6′-dhbp; <b>3</b>_<b>A</b>: N,N = 2,3-dihydro-[1,4]­dioxino­[2,3-<i>f</i>]­[1,10]­phenanthroline (dop) and PL = 6,6′-dhbp; <b>4</b>_<b>A</b>: N,N = bipy and PL = 4,4′-dimethyl-6,6′-dihydroxybipyridine (dmdhbp); <b>5</b>_<b>A</b>: N,N = 1,10-phenanthroline (phen) and PL = 4,4′-dihydroxybipyridine (4,4′-dhbp). The thermodynamic acidity of these complexes was measured in terms of two p<i>K</i>_a values for conversion from the acidic form (<b>X</b>_<b>A</b>) to the basic form (<b>X</b>_<b>B</b>) by removal of two protons. Single-crystal X-ray diffraction data is discussed for <b>2</b>_<b>A</b>, <b>2</b>_<b>B</b>, <b>3</b>_<b>A</b>, <b>4</b>_<b>B</b>, and <b>5</b>_<b>A</b>. All complexes except <b>5</b>_<b>A</b> showed measurable photodissociation with blue light (λ = 450 nm). For complexes <b>1</b>_<b>A</b>–<b>4</b>_<b>A</b> and their deprotonated analogues (<b>1</b>_<b>B</b>–<b>4</b>_<b>B</b>), the protonated form (at pH 5) consistently gave faster rates of photodissociation and larger quantum yields for the photoproduct, [(N,N)₂Ru­(H₂O)₂]²⁺. This shows that low pH can lead to greater rates of photodissociation. Cytotoxicity studies with <b>1</b>_<b>A</b>–<b>5</b>_<b>A</b> showed that complex <b>3</b>_<b>A</b> is the most cytotoxic complex of this series with IC₅₀ values as low as 4 μM (with blue light) versus two breast cancer cell lines. Complex <b>3</b>_<b>A</b> is also selectively cytotoxic, with sevenfold higher toxicity toward cancerous versus normal breast cells. Phototoxicity indices with <b>3</b>_<b>A</b> were as high as 120, which shows that dark toxicity is avoided. The key difference between complex <b>3</b>_<b>A</b> and the other complexes tested appears to be higher uptake of the complex as measured by inductively coupled plasma mass spectrometry, and a more hydrophobic complex as compared to <b>1</b>_<b>A</b>, which may enhance uptake. These complexes demonstrate proof of concept for dual activation by both low pH and blue light, thus establishing that a pHAMP approach can be used for selective targeting of cancer cells