4 research outputs found
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)<sub>2</sub>RuÂ(PL)]<sup>2+</sup> were synthesized, fully characterized, and tested for cytotoxicity
in cell culture (<b>1</b><sub><b>A</b></sub>: N,N = 2,2′-bipyridine
(bipy) and PL, the photolabile ligand, = 6,6′-dihydroxybipyridine
(6,6′-dhbp); <b>2</b><sub><b>A</b></sub>: N,N =
1,10-phenanthroline (phen) and PL = 6,6′-dhbp; <b>3</b><sub><b>A</b></sub>: N,N = 2,3-dihydro-[1,4]ÂdioxinoÂ[2,3-<i>f</i>]Â[1,10]Âphenanthroline (dop) and PL = 6,6′-dhbp; <b>4</b><sub><b>A</b></sub>: N,N = bipy and PL = 4,4′-dimethyl-6,6′-dihydroxybipyridine
(dmdhbp); <b>5</b><sub><b>A</b></sub>: 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><sub>a</sub> values for conversion from
the acidic form (<b>X</b><sub><b>A</b></sub>) to the basic
form (<b>X</b><sub><b>B</b></sub>) by removal of two protons.
Single-crystal X-ray diffraction data is discussed for <b>2</b><sub><b>A</b></sub>, <b>2</b><sub><b>B</b></sub>, <b>3</b><sub><b>A</b></sub>, <b>4</b><sub><b>B</b></sub>, and <b>5</b><sub><b>A</b></sub>. All
complexes except <b>5</b><sub><b>A</b></sub> showed measurable
photodissociation with blue light (λ = 450 nm). For complexes <b>1</b><sub><b>A</b></sub>–<b>4</b><sub><b>A</b></sub> and their deprotonated analogues (<b>1</b><sub><b>B</b></sub>–<b>4</b><sub><b>B</b></sub>), the protonated form (at pH 5) consistently gave faster rates of
photodissociation and larger quantum yields for the photoproduct,
[(N,N)<sub>2</sub>RuÂ(H<sub>2</sub>O)<sub>2</sub>]<sup>2+</sup>. This
shows that low pH can lead to greater rates of photodissociation.
Cytotoxicity studies with <b>1</b><sub><b>A</b></sub>–<b>5</b><sub><b>A</b></sub> showed that complex <b>3</b><sub><b>A</b></sub> is the most cytotoxic complex of this series
with IC<sub>50</sub> values as low as 4 μM (with blue light)
versus two breast cancer cell lines. Complex <b>3</b><sub><b>A</b></sub> is also selectively cytotoxic, with sevenfold higher
toxicity toward cancerous versus normal breast cells. Phototoxicity
indices with <b>3</b><sub><b>A</b></sub> were as high
as 120, which shows that dark toxicity is avoided. The key difference
between complex <b>3</b><sub><b>A</b></sub> 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><sub><b>A</b></sub>, 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