Evaluation of cardiovascular risk in patients with Parkinson disease under levodopa treatment

Background Levodopa is the indispensable choice of medial therapy in patients with Parkinson disease (PD). Since L-dopa treatment was shown to increase serum homocysteine levels, a well-known risk factor for cardiovascular disorders, the patients with PD under L-dopa treatment will be at increased risk for future cardiovascular events. The objective of this study is to evaluate cardiovascular risk in patients with PD under levodopa treatment. Methods The study population consisted of 65 patients with idiopathic PD under L-dopa treatment. The control group included 32 age and gender matched individuals who had no cognitive decline. Echocardiographic measurements, serum homocysteine levels and elastic parameters of the aorta were compared between the patients with PD and controls. Results As an expected feature of L-dopa therapy, the Parkinson group had significantly higher homocystein levels (15.1 ± 3.9 μmol/L vs. 11.5 ± 3.2 μmol/L, P = 0.02). Aortic distensibility was significantly lower in the patients with PD when compared to controls (4.8 ± 1.5 dyn/cm² vs. 6.2 ± 1.9 dyn/cm², P = 0.016). Additionally, the patients with PD had higher aortic strain and aortic stiffness index (13.4% ± 6.4% vs. 7.4% ± 3.6%, P < 0.001 and 7.3 ± 1.5 vs. 4.9 ± 1.9, P < 0.001, respectively). Furthermore, serum homocysteine levels were found to be positively correlated with aortic stiffness index and there was a negative correlation between aortic distensibility and levels of serum homocysteine (r = 0.674, P < 0.001; r = -0.602, P < 0.001, respectively). Conclusions The patients with PD under L-dopa treatment have increased aortic stiffness and impaired diastolic function compared to healthy individuals. Elevated serum homocysteine levels may be a possible pathophysiological mechanism.     

Association between serum homocysteine and arterial stiffness in elderly: a community-based study

Background Arterial stiffness and homocysteine are both powerful predictors of cardiovascular disease, especially in older popula tions. Previous studies have investigated the association of homocysteine with arterial stiffness in human subjects, while the relationship between homocysteine and arterial stiffness in the elderly is still indefinite. The current study examined the association of homocysteine with arterial stiffness in Chinese community-based elderly persons. Methods We related serum levels of homocysteine to two measures of arte- rial stiffness （carotid-femoral pulse wave velocity （PWV） and carotid-radial PWV） in 780 participants （46.3% men, mean age 71.9 years （ranging 65-96 years old）） from two communities of Beijing, China. Arterial stiffness were measured within two days of the time of bio- marker measurement. Results In multiple-adjusted models, homocysteine levels was strongly associated with the carotid-femoral PWV （standardized 13 = 0.13, P 〈 0.001）, even after adjustment for classical risk factors of cardiovascular disease. The association is also stronger when the carotid-femoral PWV is elevated above normal, whereas no significant association with homocysteine was observed for ca-rotid-radial PWV. Conclusions In Chinese elderly persons, serum homocysteine levels are associated with alterations of aortic stiffness.     

Serum uric acid as a prognostic marker in the setting of advanced vascular disease: a prospective study in the elderly

Background Many epidemiological studies analyze the relationship between hyperuricemia and cardiovascular outcomes. This observational prospective study investigates the association of serum uric acid (SUA) levels with adverse cardiovascular events and deaths in an elderly population affected by advanced atherosclerosis. Methods Two hundred and seventy six elderly patients affected by advanced atherosclerosis (217 males and 59 females; aged 71.2 ± 7.8 years) were included. All patients were assessed for history of cardiovascular disease, cancer, obesity and traditional risk factors. Patients were followed for approximately 31 ± 11 months. Major events were recorded during follow-up, defined as myocardial infarction, cerebral ischemia, myocardial and/or peripheral revascularization and death. Results Mean SUA level was 5.47 ± 1.43 mg/dL; then we further divided the population in two groups, according to the median value (5.36 mg/dL). During a median follow up of 31 months (5 to 49 months), 66 cardiovascular events, 9 fatal cardiovascular events and 14 cancer-related deaths have occurred. The patients with increased SUA level presented a higher significant incidence of total cardiovascular events (HR: 1.867, P = 0.014, 95%CI: 1.134–3.074). The same patients showed a significant increased risk of cancer-related death (HR: 4.335, P = 0.025, 95%CI: 1.204–15.606). Conclusions Increased SUA levels are independently and significantly associated with risk of cardiovascular events and cancer related death in a population of mainly elderly patients affected by peripheral vasculopathy.     

Effect of Exercise on Blood Pressure in Type 2 Diabetes: A Randomized Controlled Trial

BACKGROUND

Increased blood pressure (BP) in type 2 diabetes (T2DM) markedly increases cardiovascular disease morbidity and mortality risk compared to having increased BP alone.

OBJECTIVE

To investigate whether exercise reduces suboptimal levels of untreated suboptimal BP or treated hypertension.

DESIGN

Prospective, randomized controlled trial for 6 months.

SETTING

Single center in Baltimore, MD, USA.

PATIENTS

140 participants with T2DM not requiring insulin and untreated SBP of 120–159 or DBP of 85–99 mmHg, or, if being treated for hypertension, any SBP <159 mmHg or DBP < 99 mmHg; 114 completed the study.

INTERVENTION

Supervised exercise, 3 times per week for 6 months compared with general advice about physical activity.

MEASUREMENTS

Resting SBP and DBP (primary outcome); diabetes status, arterial stiffness assessed as carotid-femoral pulse-wave velocity (PWV), body composition and fitness (secondary outcomes).

RESULTS

Overall baseline BP was 126.8 ± 13.5 / 71.7 ± 9.0 mmHg, with no group differences. At 6 months, BP was unchanged from baseline in either group, BP 125.8 ± 13.2 / 70.7 ± 8.8 mmHg in controls; and 126.0 ± 14.2 / 70.3 ± 9.0 mmHg in exercisers, despite attaining a training effects as evidenced by increased aerobic and strength fitness and lean mass and reduced fat mass (all p < 0.05), Overall baseline PWV was 959.9 ± 333.1 cm/s, with no group difference. At 6-months, PWV did not change and was not different between group; exercisers, 923.7 ± 319.8 cm/s, 905.5 ± 344.7, controls.

LIMITATIONS

A completion rate of 81 %.

CONCLUSIONS

Though exercisers improve fitness and body composition, there were no reductions in BP. The lack of change in arterial stiffness suggests a resistance to exercise-induced BP reduction in persons with T2DM.KEY WORDS: exercise training, diabetes, high blood pressure, randomized trial     

Tibolone inhibits aortic atherosclerotic lesionformation in oophorectomized cholesterol-fed rabbits

BACKGROUND:

Tibolone is a synthetic steroid effective for the treatment of climacteric symptoms and osteoporosis. Long term treatment with tibolone is associated with a significant decrease in cholesterol levels due to a parallel decrease in high-density lipoprotein. However, the effect of these changes on atherogenesis is not known.

OBJECTIVE:

To investigate the effect of tibolone therapy on aorta atherogenesis.

MATERIAL AND METHODS:

Thirty-two New Zealand white rabbits were fed cholesterol-rich feed and studied for four months. The rabbits underwent laparotomy and were randomly assigned to four groups. Twenty-four rabbits underwent bilateral ovariectomy; of these, eight received tibolone (group T), eight received estradiol valerate (group E), eight received placebo after sterilization (group C), and eight were sham operated (group S).

RESULTS:

After receiving the cholesterol-rich diet, total levels of cholesterol increased in group C from 3.17±0.72 mmol/L to 35.36±9.01 mmol/L, in group S from 2.88±0.9 mmol/L to 28.76±9.442 mmol/L, in group E from 1.69±0.44 mmol/L to 1.69±0.44 mmol/L and in group T from 2.03±0.22 mmol/L to 26.33±13.45 mmol/L (no significant differences were observed among the groups at the end of the study). At four months, the cholesterol- rich diet caused atherosclerotic lesions in both treated and untreated rabbits, affecting 30.47±12.2%, 24.51±16.1%, 17.91±10.19% and 10.21±6.8% of the aortic surface for groups C, S, E and T, respectively (P<0.01 for treated groups).

CONCLUSION:

The principal result from this study was that treatment with tibolone in cholesterol-fed ovariectomized rabbits reduces aortic atherosclerotic lesion formation and that this reduction is not related to plasma lipid levels.     

Complex porcine model of atherosclerosis: Induction of early coronary lesions after long-term hyperlipidemia without sustained hyperglycemia

BACKGROUND:

The incidence of coronary artery disease (CAD) is still increasing in industrialized countries and it is even higher in diabetic patients. For experimental studies investigating the pathophysiology of CAD, the use of an animal model comparable with the pathological situation in patients is crucial.

OBJECTIVE:

To develop a model of advanced coronary atherosclerosis with induction of hyperlipidemia and hyperglycemia in domestic pigs.

METHODS:

Six pigs were fed a standard pig chow (controls), two were fed a 2% cholesterol and 17% coconut fat diet (Chol group), and two pigs received a 4% cholesterol and 17% coconut fat diet combined with streptozotocin (STZ) injections to induce diabetes (High Chol+STZ group). Serum lipid and plasma glucose values were analyzed, and histochemical staining for morphometric analysis and immunohistochemistry were performed.

RESULTS:

Pigs on the hyperlipidemic diet had elevated mean (± SD) serum lipid levels (total cholesterol 5.05±1.45 mmol/L [Chol] and 5.03±2.41 mmol/L [High Chol+STZ] versus 2.09±0.23 mmol/L [controls]). Histopathological evaluation revealed an initial stage of coronary atherosclerosis. None of the STZ-treated pigs showed a sustained elevation of plasma glucose (mean glucose before STZ injection was 5.11±0.94 mmol/L and thereafter was 6.03±2.39 mmol/L) or a decline in pancreatic beta cells.

CONCLUSIONS:

The current data suggest that the domestic porcine model is not suitable to create severe CAD using an atherogenic diet in combination with STZ injections for experimental interventional vascular research. This may be due to different STZ sensitivities among species. However, hyperlipidemia induced early pathological lesions in coronary arteries resembling initial stages of atherosclerosis without severe luminal narrowing.     

Clinical diagnosis of pandemic A(H1N1) 2009 influenza in children with negative rapid influenza diagnostic test by lymphopenia and lower C‐reactive protein levels

Background

The sensitivity of rapid influenza diagnostic test (RIDT) of children with influenza-like illness (ILI) remains low.

Objective

We compare the parameters between pandemic A(H1N1) 2009 influenza with negative RIDT and ILI not H1N1 for improving the low sensitivity of RIDT for children with ILI.

Methods

In a cohort of consecutive laboratory-confirmed H1N1 influenza, we identified 150 H1N1 children with positive RIDT, 152 H1N1 children with negative RIDT, and 75 children with ILI not H1N1. Viral load in throat, complete blood count (CBC), and C-reactive protein (CRP) levels between H1N1 children with negative RIDT and children with ILI not H1N1 were assessed.

Results

The diagnostic sensitivity of the RIDT was 45·5%. An analysis of CBC and CRP levels indicated that H1N1 children with negative RIDT had lower total leukocyte, neutrophil, lymphocyte, and basophil counts, and serum CRP levels (P < 0·01). Lymphocyte counts less than 1500 cells/mm³ and CRP levels <15 mg/l, determined by a receiver operating characteristic curve, showed a diagnostic sensitivity of 52·5% and 80·7%, respectively. Combining the lymphocyte counts and CRP levels provided a diagnostic sensitivity of 91·5%. Moreover, H1N1 children with negative RIDT had a lower viral load than those with positive RIDT (3·33 versus 4·48 log₁₀ copies/ml, P < 0·001); the viral load was negatively correlated to the lymphocyte count (P < 0·001).

Conclusions

A combination of a low lymphocyte count and a low CRP level could, in the early disease phase, provide a useful screening for H1N1 children with false-negative RIDT, potentially facilitating differential diagnoses.     

Outcome of blood pressure and renal function in patients with renal artery stenosis after stenting

OBJECTIVE

To study the response of systolic and diastolic blood pressure (BP) and renal function after renal artery stenting at three months, six months, one year and last follow-up.

METHODS

Patients with significant renal artery stenosis who underwent angioplasty with stenting from January 1999 to September 2006 were analyzed. The BP and serum creatinine levels were recorded at baseline, three months, six months, one year and at last follow-up. Generalized estimating equations were applied to analyze the changes in blood pressure and serum creatinine over time.

RESULTS

There were 32 patients – 21 Chinese, six Malay and five Indian. The male to female ratio was 1.3:1. The mean age (± SD) was 69.4±8.8 years. The mean follow-up time was 1.8±1.6 years (range 0.5 to six years). When compared with the baseline BP, there was significant improvement at three months, six months, one year and at last follow-up. In the diabetes mellitus (DM) group, there was deterioration in serum creatinine. In the non-DM group, there was stabilization of serum creatinine with improvement at one year.

CONCLUSION

Significant improvement in BP occurs in renal artery stenosis patients after stenting. In patients without DM, renal function remains stable or improves. However, in DM patients, especially those with proteinuria, there is deterioration in renal function.     

Effects of three and eight weeks oral administration of bis(maltolato)oxovanadium(IV) on plasma homocysteine and cysteine levels in streptozotocin-induced diabetic rats

BACKGROUND:

Diabetes mellitus is one of the leading causes of illness and death in North America. Cardiovascular diseases are a common secondary complication in the diabetic population. One of the important risk factors identified for the development of cardiovascular disease is an elevation in the sulfur amino acid, homocysteine. Although the exact mechanism(s) that underlie the relationship between elevated plasma homocysteine levels and cardiovascular disease remain unclear, it has been suggested that endothelial dysfunction produced by modestly elevated blood homocysteine concentrations may account for an increased risk of both arterial and venous occlusive disease.

OBJECTIVES:

The present study examined the effects of three- and eight-weeks bis(maltolato)oxovanadium(IV) (BMOV) treatment on plasma concentrations of homocysteine and cysteine in both control and streptozotocin (STZ) diabetic rats.

METHODS:

Diabetes was induced in male Wistar rats by a single intravenous injection of STZ (60 mg/kg) in normal saline. Control animals received normal saline only. Animals were further randomized into treated and untreated groups. Treated animals received BMOV orally, dissolved in tap water, while untreated animals only received tap water. Three or eight weeks postinduction of diabetes, blood samples were obtained by cardiac puncture from the animals. Plasma harvested from each blood sample was used to determine glucose, insulin, homocysteine and cysteine concentrations.

RESULTS:

There was a significant decrease in plasma homocysteine levels in the diabetic (three- and eight-week study) groups compared with their respective controls (three-week study: diabetic group 3.1±0.7 μmol/L and control group 6.1±0.7 μmol/L; eight-week study: diabetic group 4.3±0.5 μmol/L and control group 6.9±1.0 μmol/L). Plasma cysteine levels were significantly decreased in the diabetic and diabetic treated groups (eight-week study) compared with their respective control groups (diabetic group 90.2±32.3 μmol/L and control group 177.9±36.7 μmol/L). BMOV treatment restored plasma homocysteine concentrations in diabetic animals to concentrations found in nondiabetic animals.

CONCLUSIONS:

Taken together, these findings suggest that STZ-induced diabetes may result in decreased plasma homocysteine and cysteine levels and that BMOV treatment may increase plasma homocysteine concentrations to nondiabetic concentrations. These results may provide further insight on how this insulin-enhancing/mimetic agent modifies plasma homocysteine metabolism.     

Clinic accessibility and clinic‐level predictors of the geographic variation in 2009 pandemic influenza vaccine coverage in Montreal,Canada

Background

Nineteen mass vaccination clinics were established in Montreal, Canada, as part of the 2009 influenza A/H1N1p vaccination campaign. Although approximately 50% of the population was vaccinated, there was a considerable variation in clinic performance and community vaccine coverage.

Objective

To identify community- and clinic-level predictors of vaccine uptake, while accounting for the accessibility of clinics from the community of residence.

Methods

All records of influenza A/H1N1p vaccinations administered in Montreal were obtained from a vaccine registry. Multivariable regression models, specifically Bayesian gravity models, were used to assess the relationship between vaccination rates and clinic accessibility, clinic-level factors, and community-level factors.

Results

Relative risks compare the vaccination rates at the variable''s upper quartile to the lower quartile. All else being equal, clinics in areas with high violent crime rates, high residential density, and high levels of material deprivation tended to perform poorly (adjusted relative risk [ARR]: 0·917, 95% CI [credible interval]: 0·915, 0·918; ARR: 0·663, 95% CI: 0·660, 0·666, ARR: 0·649, 95% CI: 0·645, 0·654, respectively). Even after controlling for accessibility and clinic-level predictors, communities with a greater proportion of new immigrants and families living below the poverty level tended to have lower rates (ARR: 0·936, 95% CI: 0·913, 0·959; ARR: 0·918, 95% CI: 0·893, 0·946, respectively), while communities with a higher proportion speaking English or French tended to have higher rates (ARR: 1·034, 95% CI: 1·012, 1·059).

Conclusion

In planning future mass vaccination campaigns, the gravity model could be used to compare expected vaccine uptake for different clinic location strategies.     

Comparison of the effects of different magnesium administration times on infarct size

BACKGROUND:

The protection of high magnesium on infarct size remains controversial.

OBJECTIVE:

To examine the effects of magnesium administered before ischemia or early in reperfusion on infarct size in a rat model of global ischemia

METHODS:

Isolated rat hearts were submitted to 40 min of normothermic global ischemia and 2 h of reperfusion. After 20 min of stabilization, four protocols were performed: ischemic control (IC) hearts; 15 mM of magnesium chloride administered 15 min before ischemia (MgI); 15 mM of magnesium chloride administered during the first 15 min of reperfusion (MgR); or 15 mM magnesium plus 5 mM calcium (Mg+Ca) before ischemia. Infarct size was measured by triphenyltetrazolium staining. Contractile function was assessed by left ventricular developed pressure and the maximal velocity of rise of left ventricular presssure.

RESULTS:

The infarct size in IC hearts was 44±5%. In MgI and MgR hearts, the infarct diminished to 4.5±1.5% and 18±4%, respectively. In Mg+Ca hearts, the protection was also obtained (19±3%). Myocardial function also improved significantly by magnesium treatment. At the end of reperfusion, left ventricular developed pressure and maximal velocity of rise of left ventricular pressure values were 23±6% and 22±3% in MgI; and 10±3% and 9±2.6% in MgR versus 2±0.7% and 2.3±0.8% in IC hearts, respectively.

CONCLUSION:

The treatment with magnesium either before ischemia or early in reperfusion has an infarct size limiting effect in a model of global ischemia. This protective effect is partially due to its calcium antagonistic action.     

Prenatal influenza exposure and cardiovascular events in adulthood

Objectives

This study examined the association between prenatal exposure to pandemic influenza and cardiovascular events in adulthood.

Design

Using Danish surveillance data to identify months when influenza activity was highest during three previous pandemics (1918, 1957, and 1968), persons were defined as exposed/unexposed based on whether they were in utero during peak months of one of the pandemics. Episodes of acute myocardial infarction (MI) and stroke were identified in the Danish National Registry of Patients covering all Danish hospitals since 1977.

Setting/Sample

Information from Danish national registries on all persons with a Civil Personal Registry number and birthdates in 1915 through 1922, 1954 through 1960, and 1966 through 1972 was collected.

Main outcome measures

Crude incidence rate ratios (IRRs) were calculated per pandemic. Generalized linear models were fit to estimate IRRs adjusted for sex.

Results

For acute MI, sex-adjusted IRRs for persons in utero during peaks of the 1918, 1957, and 1968 pandemics, compared with those born afterward, were 1·02 (95% confidence interval (CI): 0·99, 1·05), 0·96 (95% CI: 0·87, 1·05), and 1·18 (95% CI: 0·96, 1·45), respectively. For stroke, the corresponding IRRs were 0·99 (95% CI: 0·97, 1·02), 0·99 (95% CI: 0·92, 1·05), and 0·85 (95% CI: 0·77, 0·94), respectively.

Conclusions

There was generally no evidence of an association between prenatal influenza exposure and acute MI or stroke in adulthood. However, survivor bias and left truncation of outcomes for the 1918 pandemic are possible, and the current young ages of persons included in the analyses for the 1957 and 1968 pandemics may warrant later re-evaluation.     

Plasma homocysteine levels are independently associated with alterations of large artery stiffness in men but not in women

Objectives To investigate the associations of the plasma homocysteine (HCY) levels with the alterations in arterial stiffness in a community-based cohort. The gender differences in these associations were examined. Methods We evaluated the relationship between plasma HCY levels to three measures of vascular function [carotid-femoral pulse wave velocity (CF-PWV), carotid-ankle PWV (CA-PWV) and heart rate corrected augmentation index (AI)] in 1680 participants (mean age: 61.5 years; 709 men, 971 women) from communities of Beijing, China. Results In univariate analysis, plasma HCY levels was positively related to the CF-PWV (r = 0.211, P < 0.0001) and CA-PWV (r = 0.148, P < 0.0001), whereas inversely associated with AI (r = ?0.052, P = 0.016). In multiple linear regression models adjusting for covariants, plasma HCY remained positively related to the CF-PWV (standardized β = 0.065, P = 0.007) in total cases. When the groups of men and women were examined separately, plasma HCY remained positively associated with the CF-PWV (standardized β = 0.082, P = 0.023) in men, whereas the relations between HCY and any of the arterial stiffness indices were not further present in women. Conclusions In Chinese population, plasma HCY levels are independently associated with alterations of large artery stiffness in men but not in women.     

Sex differences in resource use after on-pump and off-pump coronary artery bypass surgery: A propensity score-matched cohort

BACKGROUND:

Previous studies have demonstrated that off-pump coronary artery bypass surgery (OPCAB) is associated with less use of hospital resources compared with on-pump coronary artery bypass surgery (ONCAB).

OBJECTIVE:

To determine whether there is a sex effect between the two procedures regarding resource utilization.

METHODS:

Between 1996 and 2004, 13,522 patients (10,637 men and 2885 women) underwent coronary artery bypass grafting surgery at the Toronto General Hospital (Toronto, Ontario). Among the men, 10,121 patients underwent ONCAB and 516 underwent OPCAB. The female population consisted of 2723 ONCAB and 162 OPCAB patients. Both groups were matched to standard preoperative risk factors. A propensity score macro-matched 471 OPCAB men to 471 ONCAB men, and 148 OPCAB women to 148 ONCAB women.

RESULTS:

The mean (± SD) postoperative length of stay (7.5±6.5 days versus 6.4±5.5 days; P<0.0001) was significantly higher in ONCAB compared with OPCAB in the male population. The mean length of stay in the intensive care unit and the mean ventilation time was similar between the groups. However, in the female population, there were no differences in mean posoperative length of stay (8±5.9 days versus 8±6 days; P=0.4), mean length of stay in the intensive care unit (43±38 h versus 53±81 h; P=0.4) or mean ventilation time (9.8±9.7 h versus 11±13 h; P=0.8).

CONCLUSION:

These results suggest that the benefits of OPCAB in terms of hospital resource use are influenced by sex. The potential beneficial effects are not demonstrated in the female population.     

Serum erythropoietin level and mortality in kidney transplant recipients

Summary

Background and objectives

Posttransplant anemia is frequently reported in kidney transplant recipients and is associated with worsened patient survival. Similar to high erythropoiesis-stimulating agent requirements, resistance to endogenous erythropoietin may be associated with worse clinical outcomes in patients with ESRD. We examined the association between serum erythropoietin levels and mortality among kidney transplant recipients.

Design, setting, participants, & measurements

We collected sociodemographic, clinical, medical, and transplant history and laboratory data at baseline in 886 prevalent kidney transplant recipients (mean age 51 ± 13 [SD] years, 60% men, 21% diabetics). A solid-phase chemiluminescent immunometric assay was used to measure serum erythropoietin. Cox proportional hazards regression was used to model the association between baseline serum erythropoietin levels and all-cause mortality risk.

Results

During the median 39-month follow-up, 99 subjects died. The median serum erythropoietin level was 10.85 U/L and hemoglobin was 137 ± 16 g/L. Mortality rates were significantly higher in patients with higher erythropoietin levels (crude mortality rates in the highest to lowest erythropoietin tertiles were 51.7, 35.5, and 24.0 per 1000 patient-years, respectively [P = 0.008]). In unadjusted and also in adjusted Cox models each SD higher serum erythropoietin level significantly predicted all-cause mortality: HR_{1SD increase} 1.22 and 1.28, respectively. In adjusted Cox models each SD higher serum erythropoietin/blood hemoglobin ratio also significantly predicted all-cause mortality: HR_{1SD increase} 1.32. Serum erythropoietin predicted mortality in all analyzed subgroups.

Conclusions

In this sample of prevalent kidney transplant recipients, higher serum erythropoietin levels were associated with increased mortality.     

Imbalanced globin chain synthesis determines erythroid cell pathology in thalassemic mice

Background

β-thalassemia occurs from the imbalanced globin chain synthesis due to the absence or inadequate β-globin chain production. The excessive unbound α-globin chains precipitate in erythroid precursors and mature red blood cells leading to ineffective erythropoiesis and hemolysis.

Design and Methods

In vitro globin chain synthesis in reticulocytes from different types of thalassemic mice was performed. The effect of imbalanced globin chain synthesis was assessed from changes of red blood cell properties including increased numbers of red blood cells vesicles and apoptotic red blood cells, increased reactive oxygen species and decreased red blood cell survival.

Results

The α/β-globin chain ratio in β^IVSII-654-thalassemic mice, 1.26±0.03, was significantly higher than that of wild type mice, 0.96±0.05. The thalassemic mice show abnormal hematologic data and defective red blood cell properties. These values were improved significantly in doubly heterozygous thalassemic mice harboring 4 copies of human β^E-globin transgene, with a more balanced globin chain synthesis, 0.92±0.05. Moreover, transgenic mice harboring 8 extra copies of the human β^E-globin transgene showed inversely imbalanced α/β-globin synthesis ratio, 0.83±0.01, that resulted in a mild β-thalassemia phenotype due to the excessive β-globin chains. The degree of ineffective erythropoiesis also correlated with the degree of imbalanced globin chain synthesis. Bone marrow and splenic erythroid precursor cells of β^IVSII-654-thalassemic mice showed increased phosphatidylserine exposure in basophilic and polychromatophilic stages, which was restored to the normal level in doubly heterozygous mice.

Conclusions

Imbalanced α/β-globin chain as a consequence of either reduction or enhancement of β-globin chain synthesis can cause abnormal red blood cell properties in mouse models.     

Reduction of postprandial glycemic excursions in patients with type 1 diabetes: a novel human insulin formulation versus a rapid-acting insulin analog and regular human insulin

Background:

Evaluation of postprandial glycemic excursions in patients with type 1 diabetes with three prandial insulins: VIAject™ (Linjeta™), an ultra-fast insulin (UFI); insulin lispro (LIS); and regular human insulin (RHI).

Methods:

After stabilization of preprandial glycemia, 18 patients received a subcutaneous injection with an individualized insulin dose prior to a meal.

Results:

Injection of UFI resulted in a more rapid insulin absorption than with either LIS or RHI (time to half-maximal insulin levels: 13.1 ± 5.2 vs 25.4 ± 7.6 and 38.4 ± 19.5 min; p = .001 vs LIS and p < .001 vs RHI, LIS vs. RHI p < .001). Maximal postprandial glycemia was lower with UFI (0–180 min; 157 ± 30 mg/dl; p = .002 vs RHI) and LIS (170 ± 42 mg/dl; p = .668 vs RHI) than after RHI (191 ± 46 mg/dl; RHI vs LIS p = .008). The difference between maximum and minimum glycemia was smaller with UFI (70 ± 17 mg/dl) than with either RHI (91 ± 33 mg/dl; p = .007 vs UFI) or LIS (89 ± 18 mg/dl; p = .011 vs UFI). Also, the area under the blood glucose profile was lower with UFI than with RHI (0–180 min; 21.8 ± 5.8 vs 28.4 ± 7.6 g·min/dl; p < .001).

Conclusions:

The rapid absorption of UFI results in a reduction of postprandial glycemic excursions.     

Oxidative injury as contributory factor for red cells storage lesion during twenty eight days of storage

Background

Storage of red blood cells at 4 °C is associated with deleterious metabolic and biochemical changes, collectively referred to as “storage lesions”. Lipid peroxidation of the red cell membrane leading to lysis contributes to these storage lesions. The aim of the present study was to investigate oxidative injury to red cells during storage for 28 days and its correlation with markers of red cell membrane damage.

Materials and methods

Samples from 30 units of red blood cells stored at 4 °C for 28 days were withdrawn aseptically on day 0, day 14 and day 28 of storage. Markers of membrane damage including plasma haemoglobin, plasma potassium and lactate dehydrogenase (LDH) concentrations and markers of oxidative injury such as malondialdehyde (MDA) levels, haemoglobin oxidation and osmotic fragility were studied in all samples.

Results

Statistically significant (p<0.001) increases in the mean values of plasma haemoglobin, plasma potassium, LDH and markers of oxidative injury such as MDA and haemoglobin oxidation were observed over the storage period of 28 days. Direct correlations of MDA and haemoglobin oxidation with membrane damage, as reflected by plasma haemoglobin concentration, were observed.

Conclusion

Oxidative injury to red blood cells during storage leads to membrane damage and lysis. The role of antioxidants in the prevention of this deleterious effect of storage warrants investigation.     

Comparison of oxygenation in peripheral muscle during submaximal aerobic exercise, in persons with COPD and healthy, matched-control persons

Objective

The purpose of this study was to compare peripheral muscle oxygenation in persons with chronic obstructive pulmonary disease (COPD) to healthy control persons, during submaximal exercise.

Methods

Eight persons with COPD (forced expiratory volume in one second [FEV₁] = 1.00 ± 0.27 L) and eight healthy control persons (FEV₁ = 1.88 ± 0.55L) performed a submaximal graded exercise test (GXT), and completed 4 min of constant load exercise (CON) at 50% of peak GXT. Measurements included oxygen uptake, heart rate, arterial oxygen saturation and peripheral muscle oxygenation (%StO₂) at rest, during exercise, and recovery.

Results

Significantly greater workloads were attained for controls compared with COPD for peak GXT and CON. No significant differences in %StO₂ were observed between groups at: rest (GXT: 29.5 ± 22.8 vs 30.4 ± 17.3%; CON: 33.3 ± 15.4 vs 35.1 ± 17.2%); peak GXT (29.4 ± 19.4 vs 26.5 ± 15.9%); 4 min of CON (25.9 ± 13.5 vs 34.5 ± 21.8%); and recovery (GXT: 46.6 ± 29.1 vs 44.3 ± 21.7%; CON: 40.9 ± 21.5 vs 44.5 ± 23.2%).

Conclusion

These results suggest that peripheral skeletal muscle oxygenation is not compromised in COPD during submaximal exercise, and limitations in exercise capacity are most likely a result of muscle disuse and poor lung function.     

Glomerular hyperfiltration and renal progression in children with autosomal dominant polycystic kidney disease

Summary

Background and objectives

The purpose of this study was to determine whether glomerular hyperfiltration (GH) occurring early in autosomal dominant polycystic kidney disease (ADPKD) is indicative of more rapid disease progression in children.

Design, setting, participants, & measurements

One hundred eighty children with ADPKD (ages 4 to 18 years) with normal renal function were examined by renal ultrasound. Renal volume was calculated using a standard formula for a modified ellipsoid. Creatinine clearance was calculated from serum creatinine and 24-hour urine creatinine. GH was defined as creatinine clearance ≥140 ml/min per 1.73 m².

Results

Thirty-two children had GH (mean age 11.4 ± 3.6 years) and 148 had normal renal function (mean age 10.8 ± 3.9 years). Patients with GH at baseline demonstrated an increased rate of total renal volume growth (β: rate of change = +19.3 ± 10.8 cm³/year) over 5 years compared with those without GH at baseline (β = −4.3 ± 7.7 cm³/year), P = 0.008. Those with GH at baseline experienced a faster decline in creatinine clearance in subsequent years (β = −5.0 ± 0.8 ml/min per 1.73 m² per year) compared with those without GH at baseline (β = +1.0 ± 0.4 ml/min per 1.73 m² per year), P < 0.0001.

Conclusions

This study revealed that occurrence of GH in ADPKD children is associated with a significantly faster decline in renal function and higher rate of kidney enlargement over time. GH combined with the increased renal volume may therefore be used as an early marker for a more severe progression of ADPKD in children.