Reprint of: Vitamin D receptor activation and prevention of arterial ageing.

In chronic kidney disease (CKD) patients, cardiovascular (CV) morbidity and mortality rate is higher than in the general population, because of frequently concomitant hypertension, peripheral vascular disease, heart failure, vascular calcification (VC), diabetes and mineral bone disease. Recently, another important factor associated to CV risk in CKD has been deeply investigated: vitamin D deficiency. Vitamin D Receptors (VDRs) are present in several systems and tissues and VDR activation is associated to positive effects, resulting in better blood pressure control and prevention of diabetic nephropathy. Unfortunately, the natural, non-selective vitamin D receptor activator (VDRA), calcitriol, is associated to higher serum calcium and phosphate levels, thus worsening CV risk in CKD. Recent data showed that the selective VDRA paricalcitol might have ameliorative CV effects. The potential positive impact of the use of paricalcitol on diabetic nephropathy, cardiac disease, hypertension, and VC may open new paths in the fight against CV disease in CKD patients.

Vitamin D receptor activation and prevention of arterial ageing.

In chronic kidney disease (CKD) patients, cardiovascular (CV) morbidity and mortality rate is higher than in the general population, because of frequently concomitant hypertension, peripheral vascular disease, heart failure, vascular calcification (VC), diabetes and mineral bone disease. Recently, another important factor associated to CV risk in CKD has been deeply investigated: vitamin D deficiency. Vitamin D Receptors (VDRs) are present in several systems and tissues and VDR activation is associated to positive effects, resulting in better blood pressure control and prevention of diabetic nephropathy. Unfortunately, the natural, non-selective vitamin D receptor activator (VDRA), calcitriol, is associated to higher serum calcium and phosphate levels, thus worsening CV risk in CKD. Recent data showed that the selective VDRA paricalcitol might have ameliorative CV effects. The potential positive impact of the use of paricalcitol on diabetic nephropathy, cardiac disease, hypertension, and VC may open new paths in the fight against CV disease in CKD patients.

Open adhesiolysis is more effective in reducing adhesion reformation than laparoscopic adhesiolysis in an experimental model.

BACKGROUND: This study compared adhesion reformation after open and laparoscopic adhesiolysis in a rat model. METHODS: Adhesions were induced by surgically creating ischaemic buttons on the peritoneal side wall. After 7 days the animals underwent laparoscopy with carbon dioxide insufflation or laparotomy to score and lyse adhesions. Peritoneal tissue and fluid were collected after 24 h in a subset of animals, and adhesion reformation was scored 7 days after lysis in the remainder. Tissue plasminogen activator (tPA), plasminogen activator inhibitor (PAI) 1, transforming growth factor (TGF) beta1 and tumour necrosis factor (TNF) alpha mRNA, and total fibrinolytic activity were assessed. The abdomen of non-operated animals was insufflated for 7, 15 or 30 min with carbon dioxide, after which tPA and PAI-1 mRNA and total fibrinolytic activity were measured. RESULTS: Animals that underwent open adhesiolysis had 60 per cent fewer reformed adhesions than the laparoscopic adhesiolysis group (P < 0.001). There were no differences in tPA activity or tPA, PAI-1 and TNF-alpha mRNA between groups, but TGF-beta1 mRNA levels were significantly increased in the open group. Carbon dioxide insufflation did not affect peritoneal tPA activity. CONCLUSION: Open adhesiolysis may be more beneficial in minimizing adhesion reformation in the management of adhesion-related complications.

Plasma adiponectin levels in chronic kidney disease patients: relation with molecular inflammatory profile and metabolic status.

BACKGROUND AND AIM: Adiponectin (ADPN) exerts anti-inflammatory and cardio protective effects and is associated with decreased cardiovascular risk, however its role in patients with chronic kidney disease is unclear. METHODS AND RESULTS: We investigated the correlation between plasma ADPN levels, the progression of CVD and CKD and the inflammatory gene expression profile of peripheral blood mononuclear cells in patients from the NephroPLIC study (a prospective study aimed at addressing the progression of cardiovascular damage in relation to kidney dysfunction). Plasma ADPN levels were directly correlated with age, HDL-C and creatinine, and inversely with BMI, triglycerides and glomerular filtration rate (GFR). Multiple regression analysis identified plasma creatinine and HDL as the independent factors associated with ADPN plasma levels. In peripheral blood mononuclear cells (PBMC), the mRNA expression of MCP-1, CD40, Cox-2, TLR4, PAI-1, TNF alpha, resistin and RAGE was up-regulated in the group with higher GFR and higher ADPN plasma levels compared to that with low GFR and ADPN plasma levels. Patients with similar GFR values showed no differences in the gene expression profile of PBMC although ADPN levels were associated with decreased CRP and IL-6 plasma levels and decreased IMT and heart left ventricular mass. CONCLUSION: In CKD patients who are not in dialysis ADPN plasma levels are associated with a reduced renal excretory function, but correlate inversely with the determinants of the metabolic syndrome such as glucose, triglycerides and BMI, and directly with HDL. Furthermore, in patients with a similar degree of renal impairment, ADPN plasma levels are associated with a better cardiometabolic profile, despite no significant difference being observed in the gene expression pattern of PBMC.

Carbohydrate-naphthalene diimide conjugates as potential antiparasitic drugs: Synthesis, evaluation and structure-activity studies.

The neglected tropical diseases Human African Trypanosomiasis and leishmaniasis are caused by infection with trypanosomatid parasites Trypanosoma brucei and Leishmania spp, respectively. The genomes of these organisms contain multiple putative G-quadruplex (G4) forming sequences which have recently been proposed to mediate processes relevant for parasite survival. Therefore, G4 could be considered as potential targets for a novel approach towards the development of antiparasitic drugs. Recently, we have demonstrated that G4 ligands such as carbohydrate naphthalene diimide conjugates (carb-NDIs) possess notable antiparasitic activity. Herein, we have synthesized a new family of carb-NDIs, characterized by significant structural variability, and evaluated their anti-parasitic activity, with special focus on T. brucei. The interaction with relevant G4 sequences was evaluated in vitro through independent biophysical methods (FRET melting assays under competing conditions with double stranded DNA, circular dichroism and fluorescence titrations). Finally, flow cytometry and confocal microscopy experiments demonstrated that the conjugates exhibit excellent uptake into T. brucei parasites, localizing in the nuclei and kinetoplasts. Promising antiparasitic activity and selectivity against control mammalian cells, together with their peculiar mechanism of action, render the carb-NDI conjugates as suitable candidates for the development of an innovative treatment of trypanosomiasis.

A neurokinin 1 receptor antagonist decreases adhesion reformation after laparoscopic lysis of adhesions in a rat model of adhesion formation.

BACKGROUND: Up to 94% of patients experience fibrous adhesions after abdominal surgery, and a significant number of these patients require a second operation for open or laparoscopic lysis of adhesions (LOA). The authors have previously shown that inhibition of the binding of tachykinin ligands to the neurokinin 1 receptor (NK-1R) using the neurokinin 1 receptor antagonist (NK-1RA) CJ-12,255 decreases primary adhesion formation and upregulates the peritoneal fibrinolytic system in a rat model. Whereas most studies have focused on the prevention of primary adhesions, few have addressed adhesion reformation after LOA. This study aimed to determine the effects of NK-1RA administration on adhesion reformation and peritoneal fibrinolytic activity after laparoscopic LOA. METHODS: Adhesions were induced in 31 rats using our previously described ischemic button model. The rats underwent laparoscopy 7 days later, during which adhesions were scored and lysed followed by administration of the NK-1RA or saline. Then 7 days after LOA, 23 rats were killed and adhesions were scored. Eight rats also were killed 24 h after the LOA to obtain peritoneal tissue and fluid, which were analyzed for tissue plasminogen activator (tPA) mRNA expression and peritoneal fibrinolytic activity by reverse transcriptase-polymerase chain reaction (RT-PCR) and bioassay, respectively. RESULTS: At laparoscopy, 79% +/- 3% of the buttons formed adhesions. In the saline-administered control animals, 42% +/- 3.2% of the buttons reformed adhesions after LOA (p < 0.05), whereas in the animals that received the NK-1RA, 18.2% +/- 3.5% of the buttons reformed adhesions (p < 0.05). As compared with control animals, NK-1RA administration increased tPA mRNA levels by 38% and fibrinolytic activity sixfold (p < 0.05; 7.0 +/- 2.1 U/ml vs 1.2 +/- 0.54 U/ml). CONCLUSIONS: When administered during laparoscopic LOA, an NK-1RA significantly upregulates peritoneal fibrinolytic activity and decreases adhesion reformation.

Are work return and leaves of absence after acetabular fractures predictable? : A retrospective study of 108 patients.

BACKGROUND: To test if complexity of acetabular fractures, pre-trauma health status, time from trauma to definitive surgery, severity of injury or job characteristics influence work resumption, return to the same professional position and time out of work. MATERIALS AND METHODS: We performed a retrospective study on patients with surgically treated acetabular fractures. Medical records were reviewed to analyse demographics, follow-up, diagnosis (Letournel classification), type of surgical treatment, co-morbidities, time from trauma to definitive surgery, American Society of Anesthesiologists physical status classification (ASA) and associated injuries. Patients were interviewed about the amount of leaves of absence and whether they returned to the same professional position. RESULTS: The study included 108 patients whose mean age was 44 ± 11 years. Median time out of work was 180 days. Eleven patients lost their job and 23 patients returned to a different professional position. Univariable analysis showed: (a) the risk of losing the job was higher for patients who had been admitted to intensive care unit (ICU) (p = 0.018), (b) returning to the identical position was more likely in patients who were older (p = 0.006), sedentary workers (p = 0.003), and with shorter time from trauma to definitive surgery (p = 0.003). Multivariable linear regression showed that leaves of absence were longer in patients with higher ASA scores, who had been admitted to ICU, or were not sedentary workers. CONCLUSIONS: Work reintegration after acetabular fractures is a main issue for the patient and social systems: only 69 % of patients returned to their previously held professional position. Time out of work was not found to be related to fracture type but to pre-trauma health status, ICU admission and sedentary jobs. LEVEL OF EVIDENCE: III.

Estimation of HDL cholesteryl ester kinetic parameters in the cebus monkey, an animal species with high plasma cholesteryl ester transfer activity.

We studied the kinetic parameters of high density lipoprotein (HDL) cholesteryl esters in the cebus monkey, an animal species with high plasma cholesteryl ester transfer activity. HDL were radiolabeled with cholesteryl [1-14C]oleate and intravenously administered to 4 cebus monkeys. The calculated fractional catabolic rate (FCR) of the HDL cholesteryl esters was 0.081 +/- 0.002 (mean +/- SD) h-1 and the calculated residence time was 12.3 +/- 0.3 h. The production or disposal rate of plasma HDL cholesteryl esters was 34.3 +/- 4.5 mumol/h. The radiolabeled cholesteryl esters were rapidly transferred from the HDL to the very low and low density lipoproteins (VLDL + LDL) and the amount of tracer in the VLDL + LDL had already reached a maximum at 3.5 +/- 0.7 h after tracer administration. The estimated fraction of VLDL + LDL cholesteryl esters derived from the HDL was 0.77 +/- 0.06. We also used radiolabeled [1,2-3H(N)]cholesteryl palmityl ether to trace HDL cholesteryl esters, but the ether tracer was more slowly cleared from the plasma and less readily transferred between plasma lipoproteins than the ester tracer.

Effects of doxazosin, an alpha 1-adrenergic inhibitor, on plasma lipid and lipoprotein levels, low density lipoprotein metabolism and cholesterol absorption in cynomolgus monkeys.

The mechanism(s) by which doxazosin, an alpha 1 inhibitor, regulates plasma low density lipoprotein cholesterol (LDL-C) and apolipoprotein B (apo B) levels were investigated in 'normocholesterolemic' (average total cholesterol (TC) of 218 mg/dl) and 'hypercholesterolemic' (average TC of 350 mg/dl) cynomolgus monkeys. Twelve weeks of doxazosin treatment (1 mg/kg per day) significantly reduced plasma TC and LDL-C levels in both groups while high density lipoprotein cholesterol and apolipoprotein A-I concentrations rose. Despite these changes in plasma lipids, LDL and HDL lipid composition was not affected by doxazosin. The reduction in LDL-C and apo B in the doxazosin-treated 'hypercholesterolemic' group was associated with a significant increase in both receptor-dependent and -independent LDL apo B fractional catabolic rates. Similar associations were noted in the 'normocholesterolemic' group. LDL apo B production or transport rate was not affected by doxazosin. Cholesterol absorption was also significantly reduced by doxazosin which may also contribute to lowering plasma LDL-C levels. These studies suggest that doxazosin treatment can produce beneficial changes in the plasma lipid profile over a wide rage of plasma cholesterol levels by up-regulating LDL fractional clearance.

The effects of doxazosin on platelet aggregation, platelet adhesion and blood coagulation in cynomolgus monkeys.

The effect of doxazosin, a selective alpha-1 adrenergic inhibitor, on hemostasis was investigated in 9 cynomolgus monkeys. During 12 weeks of doxazosin treatment (1 mg/kg per day), serum lipids, lipoprotein cholesterols, blood coagulation, platelet aggregation and template bleeding times were measured and compared with predrug values. In addition, platelet adhesion to cultured human umbilical vein endothelial cells (HUVEC) in the presence or absence of doxazosin was evaluated. Platelet aggregation was also determined in monkeys following chronic oral exposure to aspirin (162 mg/day). Doxazosin administration was associated with significant reductions in serum total cholesterol (TC) (-16%) and low density lipoprotein cholesterol (LDL-C) (-23%), while high density lipoprotein cholesterol (HDL-C) levels increased 66%. Doxazosin did not alter any parameters of blood coagulation measured; however, bleeding times were increased significantly (33%) in doxazosin-treated animals. Although collagen-stimulated platelet aggregation was not influenced by either chronic doxazosin or aspirin treatment, the maximal extent of ADP-stimulated platelet aggregation was significantly reduced (-26% and -18%, respectively) compared with the control monkeys. Platelets from untreated control animals displayed reductions in the extent of ADP-stimulated aggregation of 13% and 23%, respectively, when incubated in vitro with 200 and 300 micrograms/ml of doxazosin. Additionally, the decrease in aggregation response of platelets obtained from doxazosin-treated monkeys was accompanied by a rapid reversal of platelet aggregation. Adhesion to HUVEC by platelets isolated from doxazosin-treated animals was significantly decreased; however, adhesion was not altered when platelets from untreated control animals were incubated with HUVEC in the presence of doxazosin. Thus, the ex vivo and in vitro studies reported in this communication suggest that doxazosin administration to nonhuman primates is associated with beneficial alterations in plasma lipids, platelet aggregation, bleeding times and platelet adhesion to endothelial cells, parameters which are thought to influence risk of cardiovascular disease in both animals and humans.

Diets enriched in unsaturated fatty acids enhance apolipoprotein A-I catabolism but do not affect either its production or hepatic mRNA abundance in cynomolgus monkeys.

To determine the mechanisms whereby dietary fatty acids influence high density lipoprotein (HDL) cholesterol and apolipoprotein (apo) A-I concentrations, ten cynomolgus monkeys were fed each of three experimental diets enriched in saturated (SAT), monounsaturated (MONO), or polyunsaturated (POLY) fatty acids in a crossover design consisting of three 13-week periods, with each animal serving as its own control. Each diet contained 30% of energy as fat with 0.22 mg cholesterol/kcal and differed solely by the isocaloric substitution of fatty acids as 18% of total energy calories. The replacement of dietary saturated fatty acids with either monounsaturated or polyunsaturated fatty acids, respectively, resulted in significant reductions of plasma total cholesterol (-17%; -30%), HDL cholesterol (-32%; -41%), and apo A-I (-37%; -44%) concentrations, while no significant differences were noted in plasma lipid or apo A-I concentrations when the MONO and POLY phases were compared. Although the MONO and POLY diets were similar in their effects on plasma lipids and apolipoproteins, the HDL of monkeys fed the POLY diet, as compared with either the SAT or the MONO diets, contained more cholesteryl ester and phospholipid but less total protein, resulting in a significantly lower total lipid to protein constituent ratio. Metabolic experiments revealed that the significantly lower plasma apo A-I concentrations observed during both the MONO and POLY phases relative to SAT were directly attributable to enhanced HDL apo A-I catabolism. Conversely, neither HDL apo A-I production rates nor hepatic apo A-I mRNA concentrations were significantly affected by dietary fatty acid perturbation in this study. Taken together, these data indicate that fractional catabolic rate is the predominant mechanism by which dietary fatty acids differentially modulate circulating concentrations of HDL apo A-I in this species when all other dietary variables are held constant.

Unidirectional transfer in vivo of high-density lipoprotein cholesteryl esters to lower-density lipoproteins in the pig, an animal species without plasma cholesteryl ester transfer activity.

The metabolism of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesteryl esters (CE) was studied in the pig, an animal species without plasma cholesteryl ester transfer activity (CETA). In the first series of experiments, LDL and HDL from normocholesterolemic pigs were radiolabeled with cholesteryl (1-14C)oleate and intravenously administered to two groups of four normocholesterolemic pigs. Radioactive tracer in LDL remained associated with the LDL fraction, and there was no transfer of LDL-CE to HDL. The transport rate (which represents the production and disposal rate) of LDL-CE in normocholesterolemic pigs was 39 mumol CE/h/L. However, radiolabeled HDL-CE were transferred to LDL (25%), and 36% of the LDL-CE mass was derived from the HDL. The transport rate of HDL-CE was 54 mumol CE/h/L, and the flux of HDL-CE to LDL was 14 mumol CE/h/L. There was no accumulation of radiolabeled HDL-CE in very-low-density lipoprotein (VLDL), which suggests that there was no transfer to VLDL. However, this does not rule out the possibility that either the very low levels of VLDL-CE (< 0.09 mmol/L) or the rapid turnover rate of the VLDL pool might have prevented the accumulation of substantial amounts of tracer in VLDL. Therefore, in a second set of experiments, the kinetics of HDL-CE were studied in high-fat-and high-cholesterol-fed pigs with elevated VLDL-CE concentrations (1.92 mmol/L). Hypercholesterolemia was associated with increased transport rates of LDL-CE (165 mumol/h/L) and HDL-CE (78 mumol/h/L) and with an increased flux of HDL-CE to LDL (78 mumol/h/L).(ABSTRACT TRUNCATED AT 250 WORDS)

Role of transforming growth factor beta-1 in peritonitis-induced adhesions.

Peritonitis is a major cause of intra-abdominal adhesion formation. The overexpression of transforming growth factor beta-1 (TGF-Beta1), a potent mitogen, chemoattractant, and stimulant for collagen synthesis by fibroblasts, has been linked to tissue fibrosis at various sites throughout the body including peritoneal adhesion formation. Hence we hypothesized that the mechanism(s) involved in peritonitis-induced adhesion formation may be mediated through the upregulation of TGF-Beta1 expression. Peritonitis was induced in rats by cecal ligation and puncture, while a control group underwent sham operation. Adhesions were scored and harvested from both groups at 0, 6 and 12 hours and at 1, 2, 4, 7, and 28 days. Tissue expression of TGF-Beta1 mRNA was determined by quantitative reverse transcription-polymerase chain reaction and TGF-Beta1 protein was localized by immunohistochemical analysis. Serum and peritoneal fluid TGF-Beta1 concentrations were quantified by enzyme-linked immunosorbent assay. Compared with sham operation, peritonitis was associated with a significantly greater incidence of abdominal adhesions and a significant increase in the levels of TGF-Beta1 mRNA expression at days 2, 4, and 7. Immunostaining intensity of TGF-Beta1 in adhesions from the peritonitis group also steadily rose through day 7. In peritoneal fluid, the ratio of active:total TGF-Beta1 was significantly increased in the peritonitis group on days 1, 2, and 4 compared with the sham group. These results suggest that peritonitis is associated with the upregulation of TGF-Beta1, a mechanism that may exacerbate adhesion formation.

Role of a hyaluronate-based membrane in the prevention of peritonitis-induced adhesions.

Adhesions remain a significant postoperative complication of abdominal surgery; however, recent evidence suggests that physical barriers may reduce their incidence. Although these adhesion prevention barriers are efficacious when used under aseptic conditions, little is known about their use in the presence of peritonitis, which is associated with an increased incidence of abdominal adhesions. A sodium hyaluronate and carboxymethylcellulose bioresorbable membrane (HA membrane) has been shown recently to reduce postoperative adhesions in several animal models and in two clinical trials. To investigate the efficacy of HA membrane in the presence of peritonitis, generalized peritonitis was induced in rats by either cecal ligation and puncture (CLP) or cecal ligation (CL) alone. The ceca were resected after 12 hours, and animals were randomly assigned to receive or not receive HA membrane applied to the cecum. At day 7, abdominal adhesions and abscesses were scored. In the presence of peritonitis, HA membrane did not significantly reduce the number or tenacity of adhesions. A trend toward increased abscess formation was associated with HA membrane in the CL group. Although HA membrane has been shown to reduce the incidence and severity of abdominal adhesions under aseptic conditions, this study demonstrates that it is not efficacious in preventing abdominal adhesions in the presence of peritonitis. The association between HA membrane and abscess formation in the presence of experimental peritonitis requires further investigation.

Ileal pouch salvage following failed ileal pouch- anal anastomosis.

Attempts have been made to salvage failed ileal pouch-anal anastomoses (IPAA) performed for ulcerative colitis or familial polyposis coli. These can be categorized as total reconstruction of the IPAA, partial transabdominal approach, and partial transperineal approach. The aims of our study were to determine the overall success of pouch salvage; to examine the demographics, indications, and outcomes for each approach; and to assess anorectal physiology and patient satisfaction in those with successful salvage operations. We reviewed data, including results of anorectal manometry, from 29 patients undergoing salvage procedures for failed IPAA. Seventeen salvage attempts were successful, 11 attempts failed, and one patient was lost to follow-up. Success rates were 100% in the total reconstruction group, 25% in the partial transabdominal group, and 55% in the transperineal group. In those undergoing total reconstruction of the IPAA (n = 9), functional outcome, as measured by incontinence, improved with 50% reporting incontinence preoperatively compared to 0% postoperatively (P = 0.055). Mean 24-hour stool frequency and nighttime stool frequency declined. All patients reported satisfaction with their outcomes. Sixty percent of patients who underwent ileal pouch salvage following IPAA have been successful in avoiding permanent ileostomy. These results suggest that a continued effort to salvage failed IPAA, including the use of total reconstruction, is a viable alternative to permanent ileostomy.

The effect of exercise on plasma lipids and LDL subclass metabolism in miniature swine.

The effects of exercise on plasma lipids and lipoproteins, high density lipoprotein (HDL) subclass cholesterol levels, and low density lipoprotein (LDL) subclass composition and metabolism were studied in Yucatan miniature swine following 2 yr of training. The exercise protocol produced significant training effects. Post-heparin lipolytic activity was also significantly increased. Although plasma cholesterol and triglycerides did not differ significantly (P = 0.08) between the exercised and control groups, multivariate analysis indicated a strong association between lipoprotein lipase (LPL) and HDL2-C (P less than 0.0001). Although HDL-C levels rose only slightly (P less than 0.09) with exercise, a significant shift was noted in the distribution of cholesterol from the HDL3 to the HDL2 fractions, perhaps mediated by the substantial increase in LPL activity. Exercise had little effect on the chemical composition of the major lipoprotein classes; however, the triglyceride content of the lighter LDL1 subclass was significantly reduced. In the more dense LDL2 subclass, exercise resulted in a significant decrease in triglycerides concomitant with a significant increase in free cholesterol levels. In contrast with the small reductions in fractional catabolic rates (FCR) in either subclass, production rates of the exercised group were reduced, which accounted for the reduction in LDL subclass pool size. These data indicate that exercise produces subtle but significant changes in lipoprotein metabolism that have been previously associated with reduced risk of atherosclerosis.

Stemmed versus stemless total shoulder arthroplasty: a preliminary report and short-term results.

BACKGROUND: Although several studies have been performed on the use of various devices in total shoulder arthroplasty (TSA), no data are available in order to establish whether to prefer stemmed or stemless humeral components. Thus, the purpose of our study was to evaluate the short-term functional outcome in a cohort of subjects treated with TSA randomized to treatment with stemmed or stemless prosthesis. METHODS: In this prospective longitudinal study, we randomized to treatment with stemmed (group 1) or with stemless (group 2) humeral component in nineteen subjects (2 M and 17 F) diagnosed with humeral primary osteoarthritis with indication to TSA. We evaluated the range of movement of all the participants and the functional outcome using Constant score and simple shoulder test (SST) before and after 2 years from surgery. RESULTS: No differences were detected after 2 years from surgery in the two groups in terms of functional scores and range of motion (p > 0.05). CONCLUSION: Stemmed and stemless prostheses are comparable in terms of functional outcome. These data might be useful for the surgeon in order to choose more tissues-paring methodologies and less invasive procedures, such as stemless humeral implants.

Use of a novel vitamin D bioavailability test demonstrates that vitamin D absorption is decreased in patients with quiescent Crohn's disease.

BACKGROUND: Vitamin D deficiency is a common problem in patients with Crohn's disease (CD). The aim of this study was to determine the ability of normal subjects and patients with quiescent CD to absorb vitamin D(2) using a novel vitamin D bioavailability test. In addition, we evaluated whether the location of disease or previous surgery had any influence on the bioavailability of vitamin D(2) in CD patients. METHODS: Ten normal subjects (50% female) and 37 CD patients with quiescent disease (51% female) were included in this study. Subjects who recently received any vitamin D(2) were excluded. The vitamin D bioavailability test was performed in all subjects. After a baseline blood draw, all subjects were then given a single 50,000 IU oral dose of vitamin D(2) in a capsule formulation and had their blood drawn 12 hours later to determine serum vitamin D(2), which reflected their vitamin D(2) absorption capacity. RESULTS: Forty-two percent and 29% of CD patients were found to be either vitamin D-deficient (25-hydroxyvitamin D [25(OH)D] ≤20 ng/mL] or insufficient [25(OH)D 21-29 ng/mL], respectively. Twelve hours after ingesting 50,000 IU vitamin D(2) , vitamin D(2) levels rose from a baseline of 0.7 ± 0.7 ng/mL (mean ± SEM) to 49.8 ± 3.0 ng/mL in normal subjects. In CD patients, baseline vitamin D(2) levels rose from 0 ng/mL to 34.8 ± 2.8 ng/mL. CD patients had on average a 30% decrease in their ability to absorb vitamin D(2) (P = 0.01). Moreover, we found a wide variability of vitamin D(2) bioavailability in CD patients. Analysis of variance (ANOVA) revealed no statistical difference of vitamin D(2) bioavailability between patients in the CD subgroup stratified by the location of disease, the type of surgery, and receiving or not receiving surgery. CONCLUSIONS: More than 70% of the patients with quiescent CD were vitamin D-deficient or insufficient. The ability to absorb vitamin D(2) in CD patients is unpredictable and the only way to determine this is to perform a vitamin D bioavailability test. Use of this test may guide clinicians in administering the appropriate therapeutic dose of vitamin D for treating vitamin D deficiency in patients with CD.

LDL receptor activity is down-regulated similarly by a cholesterol-containing diet high in palmitic acid or high in lauric and myristic acids in cynomolgus monkeys.

To determine the mechanisms whereby diets differing widely in fatty acid composition affect plasma LDL cholesterol and apolipoprotein B concentrations, LDL kinetics and receptor- and nonreceptor-mediated LDL catabolism were investigated in 27 cynomolgus monkeys fed diets containing 0.05 mg cholesterol/kJ and 40% fat energy as corn oil alone (unsaturated fat diet rich in oleic and linoleic acids), nonhydrogenated coconut oil alone (saturated fat diet, rich in lauric and myristic acids) or an oil blend (rich in palmitic acid). Consumption of the oil blend and saturated fat diets significantly elevated total cholesterol, LDL cholesterol and apolipoprotein B concentrations relative to the unsaturated fat diet and the saturated fat diet significantly increased plasma total cholesterol and LDL cholesterol compared with the oil blend diet. However, despite the greater increases in plasma total cholesterol, LDL cholesterol and apolipoprotein B in the saturated fat vs. the oil blend dietary group, the receptor-mediated LDL fractional catabolic rate was comparable in the oil blend and saturated fat diet groups. In addition, consumption of the oil blend or saturated fat diet increased the production rate of LDL apolipoprotein B and nonreceptor-mediated LDL apolipoprotein B transport (disposal) relative to the unsaturated fat diet. Our data, therefore, suggest that consumption of the oil blend or saturated fat diet elevated plasma total cholesterol and LDL cholesterol relative to the unsaturated fat diet, and the oil blend diet abundant in palmitic acid seems to have down-regulated the LDL receptor as much as a more saturated fat diet abundant in lauric and myristic acids.