Determination of D/L-amino acids by zero needle voltage electrospray ionisation.

Ion formation may be made more efficient than in normal electrospray ionization (ESI) for certain classes of compounds, such as the polar amino acids Glu, Asn, His, Ser, Asp, Arg, Tyr and Lys, by adjusting the voltage of a normal ESI interface needle to zero voltage. For aspartic acid (Asp) the gain in signal-to-noise (S/N) ratio of the liquid chromatography/mass spectrometry (LC/MS) chromatograms obtained in the selective ion monitoring (SIM) mode (m/z 134) with zero needle potential was 40-50 times higher than detection at 4 kV. Ion formation at zero potential is likely to follow a mechanism related to sonic spray ionization. The utility of the zero needle voltage ESI was illustrated by determining the age of a human tooth by the aspartic acid epimerization method. The procedure involved separating the D- and L-aspartic acid of a tooth extract on a chiral HPLC column and detection by zero voltage ESI-MS3.

Severe endothelial dysfunction in young women with polycystic ovary syndrome is only partially explained by known cardiovascular risk factors.

OBJECTIVE: We aimed to assess whether metabolic abnormalities can explain endothelial dysfunction and associated cardiovascular disease risk (CVDr) in polycystic ovary syndrome (PCOS). Endothelial function, a recognized composite marker of CVDr, may be reduced in PCOS and can be precisely and noninvasively assessed by cardiovascular magnetic resonance (CMR). PATIENTS: Fourteen women with anovulatory PCOS (age [mean +/- SD] 33 +/- 4 years) and 13 controls (age: 33 +/- 6 years) with similar body mass index and regular menses. METHODS: Endothelium-dependent (flow-mediated dilatation - FMD) and -independent (glyceryl trinitrate - GTN) changes in the brachial artery area were measured using CMR in women with PCOS and controls. Arterial function was assessed twice, in the early follicular phase and mid cycle in controls and after an interval of 2 weeks in PCOS subjects. Fasting lipids, glucose, insulin and sex hormones were measured at the first visit. RESULTS: FMD was greatly reduced in women with PCOS compared to controls (-1%vs 5% and 2%vs 12%, P < 0.01) without differences in GTN responses. Risk factors were more prevalent in PCOS women and displayed significant linear relationships with FMD. PCOS status was the strongest predictor of FMD. Linear regression between PCOS and FMD remained significant after correction for all CVD risk markers linked to the metabolic syndrome. CONCLUSION: PCOS is associated with changes in CVD risk markers and pronounced endothelial dysfunction. However endothelial dysfunction with PCOS is only partly explained by recognized CVD risk markers.

Two new cobalt-zinc orthophosphate monohydrates: hydrothermal synthesis, crystal structures and thermal investigation.

Two new cobalt zinc orthophosphate hydrates with similar chemical formula, (CoxZn(1-x))3(PO4)2.H2O, but different composition and structure, have been prepared by systematic hydrothermal synthesis from the system nCo(CH3COO)2 : (1 -n)Zn(CH(3)COO)2 : 3.5H3PO4 : 2.1(CH3)2NH(CH2)3NH2:144H2O (0

Adipocyte differentiation of 3T3-L1 preadipocytes is dependent on lipoxygenase activity during the initial stages of the differentiation process.

Adipocytes play a central role in whole-body energy homoeostasis. Complex regulatory transcriptional networks control adipogensis, with ligand-dependent activation of PPARgamma (peroxisome proliferator-activated receptor gamma) being a decisive factor. Yet the identity of endogenous ligands promoting adipocyte differentiation has not been established. Here we present a critical evaluation of the role of LOXs (lipoxygenases) during adipocyte differentiation of 3T3-L1 cells. We show that adipocyte differentiation of 3T3-L1 preadipocytes is inhibited by the general LOX inhibitor NDGA (nordihydroguaiaretic acid) and the 12/15-LOX selective inhibitor baicalein. Baicalein-mediated inhibition of adipocyte differentiation was rescued by administration of rosiglitazone. Treatment with baicalein during the first 4 days of the differentiation process prevented adipocyte differentiation; supplementation with rosiglitazone during the same period was sufficient to rescue adipogenesis. Accordingly, we demonstrate that adipogenic conversion of 3T3-L1 cells requires PPARgamma ligands only during the first 4 days of the differentiation process. We show that the baicalein-sensitive synthesis of endogenous PPARgamma ligand(s) increases rapidly upon induction of differentiation and reaches a maximum on days 3-4 of the adipocyte differentiation programme. The conventional platelet- and leucocyte-type 12(S)-LOXs and the novel eLOX-3 (epidermis-type LOX-3) are expressed in white and brown adipose tissue, whereas only eLOX-3 is clearly expressed in 3T3-L1 cells. We suggest that endogenous PPARgamma ligand(s) promoting adipocyte differentiation are generated via a baicalein-sensitive pathway involving the novel eLOX-3.

Long-term use of contraceptive depot medroxyprogesterone acetate in young women impairs arterial endothelial function assessed by cardiovascular magnetic resonance.

BACKGROUND: Depot medroxyprogesterone acetate (DMPA) inhibits proliferation of ovarian follicles, resulting in anovulation and a decrease in circulating estrogen; the latter action is potentially disadvantageous to cardiovascular health. We therefore investigated the vascular effects of long-term contraceptive DMPA in young women. METHODS AND RESULTS: Endothelium-dependent (hyperemia-induced flow-mediated dilatation [FMD]) and -independent (glyceryl trinitrate [GTN]) changes in brachial artery area were measured using cardiovascular magnetic resonance in 13 amenorrheic DMPA users (>1 year use; mean age 29+/-4 years) and in 10 controls (mean age 30+/-4 years, P=0.25) with regular menstrual cycles after validation of the technique. FMD and GTN responses were measured just before repeat MPA injection and 48 hours later (n=12) in DMPA users and during menstruation and midcycle (n=9) in controls. Serum-estradiol levels (S-estradiol) were measured at both visits. FMD was reduced in DMPA users compared with controls during menstruation (1.1% versus 8.0%, respectively P<0.01) without differences in GTN responses. S-estradiol levels in DMPA users were significantly lower than in controls during menstruation (58 versus 96 pmol/L, P<0.01). High levels of circulating MPA 48 hours after injection were not linked to an additional impairment in FMD (2.0% versus 3.1%, P=0.23). Estradiol levels were significantly correlated to FMD (r=0.43, P<0.01). CONCLUSIONS: Endothelium-dependent arterial function measured by cardiovascular magnetic resonance is impaired in chronic users of DMPA, and hypoestrogenism may be the mechanism of action. DMPA might adversely affect cardiovascular health, and in particular its use in women with cardiovascular disease should be additionally evaluated.

A comparison of brachial artery reactivity measured by external and intravascular ultrasound.

External ultrasound (US), EXUS, is widely used to measure brachial artery (BA) diameter changes in the assessment of vascular function; however, it has not been compared with other imaging modalities. We simultaneously measured BA diameter responses to hyperaemic flow and nitrate using EXUS and intravascular ultrasound (US), IVUS, in 10 patients. Mean diameters measured across all time periods correlated closely (r = 0.67, p < 0.001). Percent diameter change to hyperaemia and nitrate also correlated well (r = 0.67, p < 0.01). IVUS cross-sectional area (CSA) was significantly different from that calculated from EXUS using pir(2) (23.95 +/- 4.89 vs. 20.35 +/- 4.51 mm(2), respectively, p < 0.001). Orthogonal diameters measured by IVUS were significantly different (5.45 +/- 0.85 vs. 5.17 +/- 0.79 mm, respectively, p < 0.005). In conclusion, EXUS and IVUS BA diameter measurements correlated well; however, discrepancies in absolute measurements were revealed. The cross-section of the BA is oval; therefore, deriving CSA by pir(2) is inaccurate.

Changes in body composition at menopause--age, lifestyle or hormone deficiency?

One of the major concerns of perimenopausal women is obesity-and for a good reason. Both general and abdominal obesity as well as loss of skeletal muscle (sarcopenia) are accelerated through the menopausal transition and lifestyle changes as well as sex hormone deficiency play important roles. Most well conducted clinical trials have demonstrated hormone replacement therapy induced reversal or at least impairment of menopausal changes in body composition and the common worry that it causes weight gain is unsubstantiated. Coaching of weight loss in obese individuals is often a frustrating task but is nevertheless of immense importance because of the health hazards of obesity. Through the climacteric period, short-term hormone replacement therapy, with or without androgens for preservation of muscle mass, might inhibit obesity and this is likely to boost motivation for introduction of more comprehensive and long-lasting initiatives linked to persistent weight loss and long-term health benefit.