Brenda M. Alexander

Curcumin Inhibits Platelet-Derived Growth Factor–Stimulated Vascular Smooth Muscle Cell Function and Injury-Induced Neointima Formation

Objective—Vascular smooth muscle cell (VSMC) migration, proliferation, and collagen synthesis are key events involved in the pathogenesis of cardiovascular disease. Growth factors, such as platelet-derived growth factor (PDGF) and fibroblast growth factor, released during vascular injury plays a pivotal role in regulating these events. Curcumin (diferuloyl methane), a major component of the spice turmeric (Curcuma longa), has been shown recently to have beneficial effects in chronic conditions, such as inflammation, cancer, cystic fibrosis, and Alzheimer’s disease. The objective of this study was to investigate the ability of curcumin to inhibit PDGF-stimulated migration, proliferation, and collagen synthesis in cultured VSMCs and neointima formation after carotid artery injury in rats. Methods and Results—Curcumin (1 to 25 &mgr;M) produced a concentration-dependent inhibition of PDGF-elicited VSMC migration, proliferation, and collagen synthesis assessed by chemotaxis, [3H]thymidine incorporation, and [3H]-l-proline incorporation, respectively. Curcumin blocked PDGF-induced VSMC actin-cytoskeleton reorganization, attenuated PDGF signal transduction, and inhibited the binding of PDGF to its receptors. Carotid artery neointima formation was significantly attenuated by perivascular curcumin compared with vehicle controls 14 days after injury, characterized by reduced DNA synthesis, collagen synthesis, and PDGF receptor phosphorylation. Conclusions—These data suggest that curcumin is a potent inhibitor of key PDGF-stimulated VSMC functions and may play a critical role in regulating these events after vascular injury.

A BRIEF COMMUNICATION: DNA Damages in Ovarian Surface Epithelial Cells of Ovulatory Hens

A cause-effect relationship between ovulation and common (surface) epithelial ovarian cancer has been suspected for many years. The ovarian surface epithelium apparently becomes exposed to genotoxins that are generated during the ovulatory process. Intensive egg-laying hens readily develop ovarian carcinomatosis. Indeed, elevated levels of potentially mutagenic 8-oxo-guanine adducts were detected in avian ovarian epithelial cells isolated from the apical surfaces and perimeters of preand postovulatory follicles, respectively. Internucleosomal DNA fragmentation indicative of apoptosis was evident in ovarian surface epithelial cells associated with the formative site of ovulation (stigma line) and regressive ruptured follicles. It is conceivable that a genetically altered progenitor cell with unrepaired DNA but not committed to death (i.e., a unifocal ‘‘escape’’) could give rise to a transformed phenotype. Hence, the high rate of ovarian cancer in egg-laying hens could be the consequence of genomic damages to the ovarian surface epithelium associated with incessant ovulations, thereby increasing the likelihood of mutation and clonal expansion. Exp Biol Med 230:429–433, 2005

Influence of Running and Walking on Hormonal Regulators of Appetite in Women

Nine female runners and ten walkers completed a 60 min moderate-intensity (70% VO2max) run or walk, or 60 min rest in counterbalanced order. Plasma concentrations of the orexogenic peptide ghrelin, anorexogenic peptides peptide YY (PYY), glucagon-like peptide-1 (GLP-1), and appetite ratings were measured at 30 min interval for 120 min, followed by a free-choice meal. Both orexogenic and anorexogenic peptides were elevated after running, but no changes were observed after walking. Relative energy intake (adjusted for cost of exercise/rest) was negative in the meal following running (−194 ± 206 kcal) versus walking (41 ± 196 kcal) (P = 0.015), although both were suppressed (P < 0.05) compared to rest (299 ± 308 and 284 ± 121 kcal, resp.). The average rate of change in PYY and GLP-1 over time predicted appetite in runners, but only the change in GLP-1 predicted hunger (P = 0.05) in walkers. Results provide evidence that exercise-induced alterations in appetite are likely driven by complex changes in appetite-regulating hormones rather than change in a single gut peptide.

Fos-like immunoreactivity in brain regions of domestic rams following exposure to rams or ewes

Limbic and basal forebrain-hypothalamic regions from male sheep differing in sexual performance were quantified for fos-like immunoreactivity. Rams classified as high-sexually performing (HP), low-sexually performing (LP), and male-oriented (MO) received noncontact sensory stimulation from either ewes in estrus (HP, n=5; LP, n=4; MO, n=4) or other males (HP, n=5; LP, n=4; MO, n=5) for a 4-h period on each of 3 consecutive days. Following exposure to stimulus animals on the third day, rams were euthanized and their brains were perfused with a 1% paraformaldehyde/1.5% glutaraldehyde solution and sections were analyzed for fos-like immunoreactivity. Brain regions analyzed were the medial amygdala (meAMY), medial preoptic area (mPOA), bed nucleus of the stria terminalis (BNST), and ventromedial hypothalamic nucleus (VMH). Fos-like immunoreactivity differed between groups in the mPOA and BNST but not in the meAMY or VMH. LP rams exposed to estrous ewes had more (P<.05) neurons staining positive for fos and fos-related antigens (FRA) in the mPOA and BNST than LP rams exposed to other rams or MO rams exposed to either estrous ewes or other rams. Numbers of neurons staining positive for FRA in the mPOA and BNST of LP rams exposed to estrous ewes, however, were not different (P>.05) from HP rams exposed to either estrous ewes or other rams. The similar fos-like immunoreactivity in areas important for the display of sexual behavior in HP and LP rams may reflect similar sensory input in these two groups of rams; however, LP rams, in contrast to HP rams, do not appear to respond similarly to the same sensory stimulus.

Degradable Cisplatin-Releasing Core-Shell Nanogels from Zwitterionic Poly(β -Aminoester)-Graft-PEG for Cancer Chemotherapy

Cisplatin conjugated onto macromolecules or loaded in micelles can be preferentially delivered to tumors to minimize its toxicity to healthy tissues and increase its drug efficacy. Herein, we report cisplatin-containing nanogels possibly useful for targeted delivery of cisplatin. Carboxylic acid-functionalized poly(β -aminoester)graft-poly(ethylene glycol) copolymers were synthesized by cocondensation polymerization of piperazine with 2,2-bis(acryloxymethyl)propionic acid, PEG 2,2-bis(acryloxymethyl)propionate macromonomer (mPEG). The graft copolymers formed 100–200 nm nanogels with low size-distribution by the complexation of their carboxylic groups with cisplatin. The nanogels were negatively charged and had a PEG outer layer. Thus, they had “stealth properties” suitable for in vivo applications. The nanogels had significantly lower in vitro cytotoxicity to SKOV-3 ovarian cancer cells than free cisplatin, but similar anticancer activity toward SKOV-3 tumors xenografted to immunocompromised mice.

Influence of Prepartum Fat Supplementation on Subsequent Beef Cow Reproduction and Calf Performance

Abstract High fat range supplement ( HFRS ) and HFRS with lipid from soybean soapstock (HFRS-SPH; Consolidated Nutrition, Omaha, NE) were compared with a corn-soybean meal supplement (control). In Exp. 1, primiparous cows were individually fed the control supplement (n = 12), HFRS (n = 12), or HFRS-SPH (n = 10) for 62 ± 2 d prepartum. Heifer body condition score pre- and postpartum did not differ (P=0.78) among groups. Milk production was not influenced (P=0.15) by source of supplement. Somatic cell counts, however, tended to be less (P=0.07) in HFRS-supplemented heifers than in heifers fed the control supplement. At birth, calf body temperature (P=0.8), vigor (P=0.7), and BW (P=0.6), as well as BW gain through 90 d postpartum (P=0.6), did not differ among prepartum supplementation treatments. Plasma concentrations of linoleic acid were greater (P=0.02) in fat-supplemented heifers at 30 d prepartum and at calving compared with heifers on the control treatment; however, concentrations of plasma linoleic acid returned to levels comparable with those in control heifers by 30 d postpartum. Neither number of cows cycling by 90 d postpartum (P=0.15) nor length of the postpartum interval (P=0.25) differed among treatment groups. In Exp. 2, multiparous cows were pen-fed the control supplement (n = 49), HFRS (n = 47), or HFRS-SPH (n = 49) for 59 ± 2 d prepartum. Prior to parturition, cows fed the control supplement had better body condition scores (5.8 ± 0.1; P=0.004) than cows fed either commercial supplement (5.4 ± 0.1). Calf performance (P=0.7) and conception rates (P= 0.5) did not differ among treatments. Productivity of cows and calves was not improved with provision of supplemental fat prepartum.

Secretion of platelet-activating factor by periovulatory ovine follicles

Secretion of platelet-activating factor (PAF) in vitro by ovine follicles and ovarian interstitium obtained at various times before, during and after the endogenous preovulatory surge of luteinizing hormone (LH) and ovulation was quantified by radioimmunoassay. Release of PAF by the preovulatory follicle increased within 2 h after initiation of the surge of LH. Capacity for secretion of PAF was greatest at the time of ovulation, then declined thereafter. Production of PAF by ovarian interstitium throughout the periovulatory period was relatively low and did not change with time. It appears that PAF could act as an intrafollicular mediator in the mechanisms of ovulation and(or) luteinization.

Presence and dynamics of leptin, GLP-1, and PYY in human breast milk at early postpartum.

Objective: The presence of appetite hormones, namely glucagon‐like peptide‐1 (GLP‐1), peptide YY (PYY), and leptin in breast milk may be important in infant feeding regulation and infant growth. This study evaluated whether concentrations of GLP‐1, PYY, and leptin change across a single feeding (from fore‐ to hindmilk), and are associated with maternal and infant anthropometrics.

Low-sexually performing rams but not male-oriented rams can be discriminated by cell size in the amygdala and preoptic area: a morphometric study.

Brain regions of male sheep behaviorally classified as high-sexually performing (n=10), low-sexually performing (n=8) or male-oriented (n=9) were examined to determine if differences in reproductive behavior were associated with differences in density or sizes of neurons. High-sexually performing rams actively mounted estrous ewes, low-sexually performing rams failed to mount or had long latencies to mounting estrous ewes, and male-oriented rams mounted other rams in preference to ewes in estrus. Cell densities and sizes were quantified in Nissl stained sections through the medial amygdala (meAMY), preoptic area (POA), bed nucleus of the stria terminalis (BNST), ventromedial hypothalamic nucleus (VMH), lateral geniculate nucleus (LG) and medial geniculate nucleus (MG). Multivariate discriminant analysis based on soma sizes within nuclei of known importance for reproductive behavior and/or gonadotropin release (meAMY, POA, BNST and VMH) discriminated (Wilks Lambda P<0.05) low-performing rams from high-performing and male-oriented rams, but did not discriminate (Wilks Lambda P=0.14) between high-performing and male-oriented rams. Cell size in the parvocellular and magnocellular layers of the LG along with cells of the MG, structures without a specific role in reproduction, did not discriminate any of the three behaviorally defined groups of rams (Wilks Lambda P=0.57). Density of cells present in structures important for the display of reproductive behavior (POA, meAMY, BNST) and/or gonadotropin release (POA, VMH) had no discriminating power nor did density of cells in structures important for the processing of visual (LG) or auditory (MG) stimuli. In conclusion, significant differences in sizes of cells located within nuclei that are specifically important for the display of male reproductive behavior were found in low-sexually performing rams compared to high-sexually performing and male-oriented rams. These differences may result from neuron development in utero or occur later as a consequence of endocrine factors or behavioral experience. Neuronal cell size is a critical variable that determines excitability to synaptic inputs because cell surface area varies exponentially with cell diameter. Relatively small differences in neuron diameter could relate to functionally important differences in neuronal excitability.

No Effect of Exercise Intensity on Appetite in Highly-Trained Endurance Women

In endurance-trained men, an acute bout of exercise is shown to suppress post-exercise appetite, yet limited research has examined this response in women. The purpose of this study was to investigate the effect of exercise intensity on appetite and gut hormone responses in endurance-trained women. Highly-trained women (n = 15, 18–40 years, 58.4 ± 6.4 kg, VO2MAX = 55.2 ± 4.3 mL/kg/min) completed isocaloric bouts (500 kcals or 2093 kJ) of moderate-intensity (MIE, 60% VO2MAX) and high-intensity (HIE, 85% VO2MAX) treadmill running at the same time of day, following a similar 48-h diet/exercise period, and at least 1-week apart. Blood was drawn pre-exercise (baseline), immediately post-exercise and every 20-min for the next 60-min. Plasma concentrations of acylated ghrelin, PYY3–36, GLP-1 and subjective appetite ratings via visual analog scale (VAS) were assessed at each time point. Acylated ghrelin decreased (p = 0.014) and PYY3–36 and GLP-1 increased (p = 0.036, p < 0.0001) immediately post-exercise, indicating appetite suppression. VAS ratings of hunger and desire to eat decreased immediately post-exercise (p = 0.0012, p = 0.0031, respectively), also indicating appetite suppression. There were no differences between exercise intensities for appetite hormones or VAS. Similar to males, post-exercise appetite regulatory hormones were altered toward suppression in highly-trained women and independent of energy cost of exercise. Results are important for female athletes striving to optimize nutrition for endurance performance.