The quantification of vitamin D receptors in coronary arteries and their association with atherosclerosis

Objective

The activated vitamin D receptor (VDR) may have an important role in vascular health. The objective of this study was to determine whether there is an association between the expression of VDRs in coronary arteries and the extent of diet-induced atherosclerosis.

Methods

Utilizing a cohort of 39 postmenopausal female cynomolgus monkeys with varying stages of atherosclerosis, histologic sections of the left anterior descending artery (LAD) were analyzed for plaque cross-sectional area, plaque thickness, and VDR quantity using immunohistochemical H-score analysis. The quantities of VDRs were analyzed as a continuous variable and were divided at the median intimal H-score into high vs. low groupings.

Results

In the LAD, a significant negative correlation was observed between the quantity of VDR and plaque size (both cross-sectional area [p < 0.001] and plaque thickness [p < 0.001]). Monkeys in the low VDR group had a significantly greater cross-sectional plaque area (1.2 mm²) and greater plaque thickness (0.3 mm) than those in the high VDR group (0.4 mm², p = 0.005; 0.1 mm, p = 0.003, respectively).

Conclusions

Lower concentrations of VDRs in a main coronary artery were associated with greater atherosclerotic plaque size in postmenopausal female monkeys. Given that coronary artery atherosclerosis is a major cause of coronary heart disease in postmenopausal women, further research to ascertain the relationship between VDRs and atherosclerosis is warranted.     

Plasma creatine kinase activity and glutathione after eccentric exercise

PURPOSE: This study examined whether plasma total glutathione levels could explain the intersubject variability in the creatine kinase (CK) response to eccentric exercise. We hypothesized that the increase in plasma CK activity after eccentric exercise would be lower for individuals with low plasma total glutathione (<2.5 micromol x L-1) compared with individuals with high total glutathione (>3.8 micromol x L-1), but other indicators of muscle damage would be the same between groups. METHODS: Resting blood samples were obtained over 2 d from 60 subjects and analyzed for plasma total glutathione. Eight subjects who had total glutathione values below 2.5 micromol x L-1 (LG), and nine who had values above 3.8 micromol x L-1 (HG) performed 50 maximal eccentric actions of the elbow flexors. Maximal voluntary isometric contraction (MVC), relaxed arm angle (RANG), and blood samples for CK, myoglobin (Mb), and total glutathione were obtained pre, post (except blood samples), 24, 48, 72, 96, and 120 h after exercise. RESULTS: There was a significant group-by-time interaction in analysis of MVC, RANG, total glutathione, CK, and Mb response to exercise. Although LG showed a smaller CK response to eccentric exercise compared with HG, LG also showed a smaller increase in plasma Mb, a faster recovery of MVC and RANG, and an increase in plasma total glutathione. CONCLUSION: Subjects with low plasma total glutathione levels had a smaller plasma CK and Mb response and a faster recovery from eccentric exercise compared with subjects having high plasma total glutathione levels. We suggest that a blunted inflammatory response in subjects with low plasma glutathione may be one explanation for these findings.     

Processing of radial fast spin-echo data for obtaining T2 estimates from a single k-space data set.

Radially acquired fast spin-echo data can be processed to obtain T2-weighted images and a T2 map from a single k-space data set. The general approach is to use data at a specific TE (or narrow TE range) in the center of k-space and data at other TE values in the outer part of k-space. With this method high-resolution T2-weighted images and T2 maps are obtained in a time efficient manner. The mixing of TE data, however, introduces errors in the T2-weighted images and T2 maps that affect the accuracy of the T2 estimates. In this work, various k-space data processing methods for reconstructing T2-weighted images and T2 maps from a single radial fast spin-echo k-space data set are analyzed in terms of the accuracy of T2 estimates. The analysis is focused on the effect of image artifacts, object dependency, and noise on the T2 estimates. Results are presented in computer-generated phantoms and in vivo.     

Variability in muscle size and strength gain after unilateral resistance training

PURPOSE: This study assessed variability in muscle size and strength changes in a large cohort of men and women after a unilateral resistance training program in the elbow flexors. A secondary purpose was to assess sex differences in size and strength changes after training. METHODS: Five hundred eighty-five subjects (342 women, 243 men) were tested at one of eight study centers. Isometric (MVC) and dynamic strength (one-repetition maximum (1RM)) of the elbow flexor muscles of each arm and magnetic resonance imaging (MRI) of the biceps brachii (to determine cross-sectional area (CSA)) were assessed before and after 12 wk of progressive dynamic resistance training of the nondominant arm. RESULTS: Size changes ranged from -2 to +59% (-0.4 to +13.6 cm), 1RM strength gains ranged from 0 to +250% (0 to +10.2 kg), and MVC changes ranged from -32 to +149% (-15.9 to +52.6 kg). Coefficients of variation were 0.48 and 0.51 for changes in CSA (P = 0.44), 1.07 and 0.89 for changes in MVC (P < 0.01), and 0.55 and 0.59 for changes in CSA (P < 0.01) in men and women, respectively. Men experienced 2.5% greater gains for CSA (P < 0.01) compared with women. Despite greater absolute gains in men, relative increases in strength measures were greater in women versus men (P < 0.05). CONCLUSION: Men and women exhibit wide ranges of response to resistance training, with some subjects showing little to no gain, and others showing profound changes, increasing size by over 10 cm and doubling their strength. Men had only a slight advantage in relative size gains compared with women, whereas women outpaced men considerably in relative gains in strength.     

Effect of hepatic dysfunction on oral cyclosporin pharmacokinetics in marrow transplant patients

The effect of hepatic dysfunction, defined as abnormal serum bilirubin level, on oral cyclosporin (CSP) pharmacokinetics was examined in 28 marrow transplant patients who received CSP for prophylaxis of graft-v- host disease. Serum CSP concentrations were measured by radioimmunoassay. Forty-one concentration-time courses were studied, divided among patients with no (less than 1.2 mg/dL), mild (1.2 to 2.0 mg/dL), and moderate (2.0 to 5.0 mg/dL) hepatic dysfunction. CSP elimination, as determined by elimination rate constant and clearance, was delayed in patients with moderate hepatic dysfunction compared to those with no hepatic dysfunction (P less than .05). The volume of distribution, lag time for absorption, maximum serum concentration, and time at which the maximum concentration was achieved was not affected by hepatic function. These data indicate that patients with moderate hepatic dysfunction have delayed CSP or CSP metabolite elimination and may be at higher risk for developing CSP-related toxicity.     

Dual phenotype kisspeptin-dopamine neurones of the rostral periventricular area of the third ventricle project to gonadotrophin-releasing hormone neurones

The neuropeptide kisspeptin and its G-protein-coupled receptor, Gpr54, are critical regulators of fertility. Two major populations of kisspeptin neurones exist in the rodent: one in the rostral periventricular area of the third ventricle (RP3V) and another in the arcuate nucleus. The RP3V population of kisspeptin neurones is crucial for the generation of the luteinising hormone surge that drives ovulation in females. The RP3V kisspeptin neurones are sexually dimorphic, with many more neurones in females than males, and they project to gonadotrophin-releasing hormone (GnRH) neurones. Tyrosine hydroxylase (TH) expressing neurones in the RP3V are also sexually dimorphic and are assumed to project to GnRH neurones. In the present study, we examined the coexpression of kisspeptin and TH peptides in the RP3V of dioestrous and pro-oestrous female mice. We also investigated whether kisspeptin and TH peptides colocalised in terminal appositions with GnRH neurones in the rostral preoptic area (rPOA). Approximately half of the kisspeptin neurones in the RP3V were found to also express TH and vice versa, although there was no difference between mice in dioestrus or pro-oestrus. The majority (95%) of GnRH neurones in the rPOA exhibited a close apposition from a kisspeptin fibre, whereas only one quarter exhibited a close apposition from a TH fibre. Many of the TH close appositions with GnRH neurones coexpressed kisspeptin (62-86%), although these dual-labelled appositions comprised <20% of all kisspeptin appositions on GnRH neurones. The percentage of GnRH neurones with kisspeptin, TH and double-labelled appositions did not differ between dioestrous and pro-oestrous mice. These findings indicate that a subpopulation of kisspeptin neurones expressing dopamine innervate GnRH neurones in the rPOA.     

Gastric cancer and Helicobacter pylori infection.

AIMS--To identify differences in the prevalence of Helicobacter pylori infection in different groups of patients with gastric cancer. METHODS--In total 224 cases of gastric cancer were studied: 120 (53.6%) intestinal; 69 (30.8%) diffuse; and 35 (15.6%) unclassified. Site of tumour, presence and severity of gastritis, presence and extent of intestinal metaplasia, and age and sex were also recorded. Infection by H pylori was assessed using modified Giemsa staining. RESULTS--H pylori infection was found in 96 (43%) cases. There was no significant association between infection and histological type of tumour, nor was there any significant association between infection and site of tumour, the presence of intestinal metaplasia, age, or sex. The only significant association identified was between infection and gastritis. CONCLUSIONS--These results are in broad agreement with those of other similar studies, although the overall prevalence of infection, at 43%, was lower than has been reported in some series. The findings do not support a role for H pylori in any particular subgroup of patients with gastric cancer but do not exclude a role for the organism in the pathogenesis of gastric cancer as a whole.