Association of glycaemic index and glycaemic load with type 2 diabetes, cardiovascular disease, cancer, and all-cause mortality: a meta-analysis of mega cohorts of more than 100 000 participants.

BACKGROUND: There is debate over whether the glycaemic index of foods relates to chronic disease. We aimed to assess the associations between glycaemic index (GI) and glycaemic load (GL) and type 2 diabetes, cardiovascular disease, diabetes-related cancers, and all-cause mortality. METHODS: We did a meta-analysis of large cohorts (≥100 000 participants) identified from the Richard Doll Consortium. We searched the Cochrane Library, MEDLINE, PubMed, Embase, Web of Science, and Scopus for cohorts that prospectively examined associations between GI or GL and chronic disease outcomes published from database inception to Aug 4, 2023. Full-article review and extraction of summary estimates data were conducted by three independent reviewers. Primary outcomes were incident type 2 diabetes, total cardiovascular disease (including mortality), diabetes-related cancers (ie, bladder, breast, colorectal, endometrial, hepatic, pancreatic, and non-Hodgkin lymphoma), and all-cause mortality. We assessed comparisons between the lowest and highest quantiles of GI and GL, adjusting for dietary factors, and pooling their most adjusted relative risk (RR) estimates using a fixed-effects model. We also assessed associations between diets high in fibre and whole grains and the four main outcomes. The study protocol is registered with PROSPERO, CRD42023394689. FINDINGS: From ten prospective large cohorts (six from the USA, one from Europe, two from Asia, and one international), we identified a total of 48 studies reporting associations between GI or GL and the outcomes of interest: 34 (71%) on various cancers, nine (19%) on cardiovascular disease, five (10%) on type 2 diabetes, and three (6%) on all-cause mortality. Consumption of high GI foods was associated with an increased incidence of type 2 diabetes (RR 1·27 [95% CI 1·21-1·34]; p<0·0001), total cardiovascular disease (1·15 [1·11-1·19]; p<0·0001), diabetes-related cancer (1·05 [1·02-1·08]; p=0·0010), and all-cause mortality (1·08 [1·05-1·12]; p<0·0001). Similar associations were seen between high GL and diabetes (RR 1·15 [95% CI 1·09-1·21]; p<0·0001) and total cardiovascular disease (1·15 [1·10-1·20]; p<0·0001). Associations between diets high in fibre and whole grains and the four main outcomes were similar to those for low GI diets. INTERPRETATION: Dietary recommendations to reduce GI and GL could have effects on health outcomes that are similar to outcomes of recommendations to increase intake of fibre and whole grain. FUNDING: Banting and Best and the Karuna Foundation.

Glycemic Index Versus Wheat Fiber on Arterial Wall Damage in Diabetes: A Randomized Controlled Trial.

OBJECTIVE: High cereal fiber and low-glycemic index (GI) diets are associated with reduced cardiovascular disease (CVD) risk in cohort studies. Clinical trial evidence on event incidence is lacking. Therefore, to make trial outcomes more directly relevant to CVD, we compared the effect on carotid plaque development in diabetes of a low-GI diet versus a whole-grain wheat-fiber diet. RESEARCH DESIGN AND METHODS: The study randomized 169 men and women with well-controlled type 2 diabetes to counseling on a low GI-diet or whole-grain wheat-fiber diet for 3 years. Change in carotid vessel wall volume (VWV) (prespecified primary end point) was assessed by MRI as an indication of arterial damage. RESULTS: Of 169 randomized participants, 134 completed the study. No treatment differences were seen in VWV. However, on the whole-grain wheat-fiber diet, VWV increased significantly from baseline, 23 mm3 (95% CI 4, 41; P = 0.016), but not on the low-GI diet, 8 mm3 (95% CI -10, 26; P = 0.381). The low-GI diet resulted in preservation of renal function, as estimated glomerular filtration rate, compared with the reduction following the wheat-fiber diet. HbA1c was modestly reduced over the first 9 months in the intention-to-treat analysis and extended with greater compliance to 15 months in the per-protocol analysis. CONCLUSIONS: Since the low-GI diet was similar to the whole-grain wheat-fiber diet recommended for cardiovascular risk reduction, the low-GI diet may also be effective for CVD risk reduction.

Low-carbohydrate vegan diets in diabetes for weight loss and sustainability: a randomized controlled trial.

BACKGROUND: Low-carbohydrate, high animal fat and protein diets have been promoted for weight loss and diabetes treatment. We therefore tested the effect of a low-carbohydrate vegan diet in diabetes as a potentially healthier and more ecologically sustainable low-carbohydrate option. OBJECTIVES: We sought to compare the effectiveness of a low-carbohydrate vegan diet with a moderate-carbohydrate vegetarian diet on weight loss and metabolic measures in diabetes. METHODS: One hundred and sixty-four male and female participants with type 2 diabetes were randomly assigned to advice on either a low-carbohydrate vegan diet, high in canola oil and plant proteins, or a vegetarian therapeutic diet, for 3 mo, with both diets recommended at 60% of calorie requirements. Body weight, fasting blood, blood pressure, and 7-d food records, to estimate potential greenhouse gas emissions, were obtained throughout the study with tests of cholesterol absorption undertaken at baseline and end of study on 50 participants. RESULTS: Both low-carbohydrate vegan and vegetarian diets similarly but markedly reduced body weight (-5.9 kg; 95% CI: -6.5, -5.28 kg; and -5.23 kg; 95% CI: -5.84, -4.62 kg), glycated hemoglobin (-0.99%; 95% CI: -1.07, -0.9%; and -0.88%; 95% CI: -0.97, -0.8%), systolic blood pressure (-4 mmHg; 95% CI: -7, -2 mmHg; and -6 mmHg; 95% CI: -8, -3 mmHg), and potential greenhouse gas emissions, but only for potential greenhouse gas emissions was there a significant treatment difference of -0.63 kgCO2/d (95% CI: -0.99, -0.27 kgCO2/d) favoring the low-carbohydrate vegan diet. CONCLUSIONS: Low-carbohydrate vegan and vegetarian diets reduced body weight, improved glycemic control and blood pressure, but the more plant-based diet had greater potential reduction in greenhouse gas emissions. TRIAL REGISTRATION NUMBER: clinicaltrials.gov identifier NCT02245399.

Systematic review and meta-analysis examining the relationship between postprandial hypotension, cardiovascular events, and all-cause mortality.

BACKGROUND: Postprandial hypotension (PPH) has been reported to be associated with syncope, falls, adverse cardiovascular outcomes, and increased all-cause mortality. It has been reported to have an incidence as high as 30% in the elderly and persons with diabetes. We therefore performed a meta-analysis to determine the relation of PPH with cardiovascular disease (CVD) events and all-cause mortality. OBJECTIVES: Our objective was to conduct a systematic review and meta-analysis of cohort and cross-sectional studies to determine the association of PPH with CVD and all-cause mortality. METHODS: We searched the databases MEDLINE, EMBASE, and Cochrane library up to 13 April 2022 for prospective cohort and cross-sectional studies that examined the association of PPH with CVD outcomes and all-cause mortality. Data were analyzed using the generic inverse variance method with a random-effects model. Grading of Recommendations, Assessment, Development, and Evaluation approach assessed the certainty of evidence. RESULTS: Seven studies that included 2389 participants met our inclusion criteria. PPH was associated with each outcome individually, including increased all-cause mortality, total CVD, CVD mortality, and stroke. CVD outcomes and all-cause mortality combined were also associated with PPH (RR: 1.52; 95% CI: 1.05, 2.18; P = 0.03; I2 = 77%). The certainty of evidence was graded as very low due to significant heterogeneity and the limited number of studies. CONCLUSIONS: This assessment indicates an association of PPH with CVD and all-cause mortality. Further studies are required to improve CVD and mortality estimates, but the potential seriousness of CVD and all-cause mortality as outcomes of PPH justifies more screening, diagnosis, and research.

Congestive heart failure model representing aortic banding induced hypertrophy: A study to analyse extent of pressure overload and alteration in myocardial structure and function.

Congestive Heart failure (CHF) is a severe pathology representing a major public health problem in industrialized nations which is increasing in prevalence and incidence. The aortic banding rat model provides steady progression of cardiac dysfunction under chronic pressure overload. Present study evaluated two abdominal aortic constriction techniques including constriction of aorta above renal arteries and between renal arteries. The extent of constriction was varied with 22 G and 24 G needles and the duration for evaluation of CHF was also varied by terminating the banded animals after 6 and 8 weeks of banding. Various hemodynamic, ECG and tissue parameters were evaluated after banding to see the progression of CHF. The findings revealed that the constriction of the aorta above both renal arteries with 24 G needle is a better technique amongst other tested banding techniques as the rate of progression of CHF was found to be maximum with it. On the basis of above study, it was concluded that, aortic banding above both renal arteries with 24 G needle is a better technique for induction of pressure overload and for further observation in transition of the cardiac compensatory to decompensatory phase, the duration of the model needs to be prolonged.

Supplemental Vitamins and Minerals for Cardiovascular Disease Prevention and Treatment: JACC Focus Seminar.

This is an update of the previous 2018 systematic review and meta-analysis of vitamin and mineral supplementation on cardiovascular disease outcomes and all-cause mortality. New randomized controlled trials and meta-analyses were identified by searching the Cochrane library, Medline, and Embase, and data were analyzed using random effects models and classified by the Grading of Recommendations Assessment Development and Evaluation approach. This updated review shows similar findings to the previous report for preventive benefits from both folic acid and B vitamins for stroke and has been graded with moderate quality. No effect was seen for the commonly used multivitamins, vitamin D, calcium, and vitamin C, and an increased risk was seen with niacin (with statin) for all-cause mortality. Conclusive evidence for the benefit of supplements across different dietary backgrounds, when the nutrient is sufficient, has not been demonstrated.

Selenium, antioxidants, cardiovascular disease, and all-cause mortality: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Antioxidants have been promoted for cardiovascular disease (CVD) risk reduction and for the prevention of cancer. Our preliminary analysis suggested that only when selenium was present were antioxidant mixtures associated with reduced all-cause mortality. OBJECTIVE: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to determine the effect of selenium supplementation alone and of antioxidant mixtures with or without selenium on the risk of CVD, cancer, and mortality. METHODS: We identified studies using the Cochrane Library, Medline, and Embase for potential CVD outcomes, cancer, and all-cause mortality following selenium supplementation alone or after antioxidant supplement mixtures with and without selenium up to June 5, 2020. RCTs of ≥24 wk were included and data were analyzed using random-effects models and classified by the Grading of Recommendations, Assessment, Development, and Evaluation approach. RESULTS: The meta-analysis identified 9423 studies, of which 43 were used in the final analysis. Overall, no association of selenium alone or antioxidants was seen with CVD and all-cause mortality. However, a decreased risk with antioxidant mixtures was seen for CVD mortality when selenium was part of the mix (RR: 0.77; 95% CI: 0.62, 0.97; P = 0.02), with no association when selenium was absent. Similarly, when selenium was part of the antioxidant mixture, a decreased risk was seen for all-cause mortality (RR: 0.90; 95% CI: 0.82, 0.98; P = 0.02) as opposed to an increased risk when selenium was absent (RR: 1.09; 95% CI: 1.04, 1.13; P = 0.0002). CONCLUSION: The addition of selenium should be considered for supplements containing antioxidant mixtures if they are to be associated with CVD and all-cause mortality risk reduction. This trial was registered at https://www.crd.york.ac.uk/PROSPERO/ as CRD42019138268.

Supplemental Vitamins and Minerals for CVD Prevention and Treatment.

The authors identified individual randomized controlled trials from previous meta-analyses and additional searches, and then performed meta-analyses on cardiovascular disease outcomes and all-cause mortality. The authors assessed publications from 2012, both before and including the U.S. Preventive Service Task Force review. Their systematic reviews and meta-analyses showed generally moderate- or low-quality evidence for preventive benefits (folic acid for total cardiovascular disease, folic acid and B-vitamins for stroke), no effect (multivitamins, vitamins C, D, ß-carotene, calcium, and selenium), or increased risk (antioxidant mixtures and niacin [with a statin] for all-cause mortality). Conclusive evidence for the benefit of any supplement across all dietary backgrounds (including deficiency and sufficiency) was not demonstrated; therefore, any benefits seen must be balanced against possible risks.

Cross-sectional associations between dietary intake and carotid intima media thickness in type 2 diabetes: baseline data from a randomised trial.

OBJECTIVE: To assess associations between dietary intake and carotid intima media thickness (CIMT) by carotid ultrasound (CUS), a surrogate marker of cardiovascular disease (CVD) risk, in those with type 2 diabetes. DESIGN: Cross-sectional analysis of baseline data from 325 participants from three randomised controlled trials collected in the same way. SETTING: Risk Factor Modification Centre, St. Michael's Hospital, Toronto, Canada. PARTICIPANTS: 325 participants with type 2 diabetes, taking oral antidiabetic agents, with an HbA1c between 6.5% and 8.0% at screening, without a recent cardiovascular event. MAIN OUTCOME MEASURES: CIMT by CUS and associations with dietary intake from 7-day food records, as well as anthropometric measures and fasting serum samples. RESULTS: CIMT was significantly inversely associated with dietary pulse intake (ß=-0.019, p=0.009), available carbohydrate (ß=-0.004, p=0.008), glycaemic load (ß=-0.001, p=0.007) and starch (ß=-0.126, p=0.010), and directly associated with total (ß=0.004, p=0.028) and saturated (ß=0.012, p=0.006) fat intake in multivariate regression models adjusted for age, smoking, previous CVD event, blood pressure medication, antidiabetic medication and ultrasonographer. CONCLUSIONS: Lower CIMT was significantly associated with greater consumption of dietary pulses and carbohydrates and lower total and saturated fat intake, suggesting a potential role for diet in CVD risk management in type 2 diabetes. Randomised controlled trials are anticipated to explore these associations further. TRIAL REGISTRATION NUMBER: NCT01063374.

Low-glycaemic index diet to improve glycaemic control and cardiovascular disease in type 2 diabetes: design and methods for a randomised, controlled, clinical trial.

INTRODUCTION: Type 2 diabetes (T2DM) produces macrovascular and microvascular damage, significantly increasing the risk of cardiovascular disease (CVD), renal failure and blindness. As rates of T2DM rise, the need for effective dietary and other lifestyle changes to improve diabetes management become more urgent. Low-glycaemic index (GI) diets may improve glycaemic control in diabetes in the short term; however, there is a lack of evidence on the long-term adherence to low-GI diets, as well as on the association with surrogate markers of CVD beyond traditional risk factors. Recently, advances have been made in measures of subclinical arterial disease through the use of MRI, which, along with standard measures from carotid ultrasound (CUS) scanning, have been associated with CVD events. We therefore designed a randomised, controlled, clinical trial to assess whether low-GI dietary advice can significantly improve surrogate markers of CVD and long-term glycaemic control in T2DM. METHODS AND ANALYSIS: 169 otherwise healthy individuals with T2DM were recruited to receive intensive counselling on a low-GI or high-cereal fibre diet for 3 years. To assess macrovascular disease, MRI and CUS are used, and to assess microvascular disease, retinal photography and 24-hour urinary collections are taken at baseline and years 1 and 3. Risk factors for CVD are assessed every 3 months. ETHICS AND DISSEMINATION: The study protocol and consent form have been approved by the research ethics board of St. Michael's Hospital. If the study shows a benefit, these data will support the use of low-GI and/or high-fibre foods in the management of T2DM and its complications. TRIAL REGISTRATION NUMBER: NCT01063374; Pre-results.

Consumption of a dietary portfolio of cholesterol lowering foods improves blood lipids without affecting concentrations of fat soluble compounds.

BACKGROUND: Consumption of a cholesterol lowering dietary portfolio including plant sterols (PS), viscous fibre, soy proteins and nuts for 6 months improves blood lipid profile. Plant sterols reduce blood cholesterol by inhibiting intestinal cholesterol absorption and concerns have been raised whether PS consumption reduces fat soluble vitamin absorption. OBJECTIVE: The objective was to determine effects of consumption of a cholesterol lowering dietary portfolio on circulating concentrations of PS and fat soluble vitamins. METHODS: Using a parallel design study, 351 hyperlipidemic participants from 4 centres across Canada were randomized to 1 of 3 groups. Participants followed dietary advice with control or portfolio diet. Participants on routine and intensive portfolio involved 2 and 7 clinic visits, respectively, over 6 months. RESULTS: No changes in plasma concentrations of α and γ tocopherol, lutein, lycopene and retinol, but decreased ß-carotene concentrations were observed with intensive (week 12: p = 0.045; week 24: p = 0.039) and routine (week 12: p = 0.031; week 24: p = 0.078) portfolio groups compared to control. However, cholesterol adjusted ß-carotene and fat soluble compound concentrations were not different compared to control. Plasma PS concentrations were increased with intensive (campesterol:p = 0.012; ß-sitosterol:p = 0.035) and routine (campesterol: p = 0.034; ß-sitosterol: p = 0.080) portfolio groups compared to control. Plasma cholesterol-adjusted campesterol and ß-sitosterol concentrations were negatively correlated (p < 0.001) with total and LDL-C levels. CONCLUSION: Results demonstrate that consuming a portfolio diet reduces serum total and LDL-C levels while increasing PS values, without altering fat soluble compounds concentrations. The extent of increments of PS with the current study are not deleterious and also maintaining optimum levels of fat soluble vitamins are of paramount necessity to maintain overall metabolism and health. Results indicate portfolio diet as one of the best options for CVD risk reduction. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00438425.

Effect of lowering the glycemic load with canola oil on glycemic control and cardiovascular risk factors: a randomized controlled trial.

OBJECTIVE: Despite their independent cardiovascular disease (CVD) advantages, effects of α-linolenic acid (ALA), monounsaturated fatty acid (MUFA), and low-glycemic-load (GL) diets have not been assessed in combination. We therefore determined the combined effect of ALA, MUFA, and low GL on glycemic control and CVD risk factors in type 2 diabetes. RESEARCH DESIGN AND METHODS: The study was a parallel design, randomized trial wherein each 3-month treatment was conducted in a Canadian academic center between March 2011 and September 2012 and involved 141 participants with type 2 diabetes (HbA1c 6.5%-8.5% [48-69 mmol/mol]) treated with oral antihyperglycemic agents. Participants were provided with dietary advice on either a low-GL diet with ALA and MUFA given as a canola oil-enriched bread supplement (31 g canola oil per 2,000 kcal) (test) or a whole-grain diet with a whole-wheat bread supplement (control). The primary outcome was HbA1c change. Secondary outcomes included calculated Framingham CVD risk score and reactive hyperemia index (RHI) ratio. RESULTS: Seventy-nine percent of the test group and 90% of the control group completed the trial. The test diet reduction in HbA1c units of -0.47% (-5.15 mmol/mol) (95% CI -0.54% to -0.40% [-5.92 to -4.38 mmol/mol]) was greater than that for the control diet (-0.31% [-3.44 mmol/mol] [95% CI -0.38% to -0.25% (-4.17 to -2.71 mmol/mol)], P = 0.002), with the greatest benefit observed in those with higher systolic blood pressure (SBP). Greater reductions were seen in CVD risk score for the test diet, whereas the RHI ratio increased for the control diet. CONCLUSIONS: A canola oil-enriched low-GL diet improved glycemic control in type 2 diabetes, particularly in participants with raised SBP, whereas whole grains improved vascular reactivity.

The human respiratory syncytial virus matrix protein is required for maturation of viral filaments.

An experimental system was developed to generate infectious human respiratory syncytial virus (HRSV) lacking matrix (M) protein expression (M-null virus) from cDNA. The role of the M protein in virus assembly was then examined by infecting HEp-2 and Vero cells with the M-null virus and assessing the impact on infectious virus production and viral protein trafficking. In the absence of M, the production of infectious progeny was strongly impaired. Immunofluorescence (IF) microscopy analysis using antibodies against the nucleoprotein (N), attachment protein (G), and fusion protein (F) failed to detect the characteristic virus-induced cell surface filaments, which are believed to represent infectious virions. In addition, a large proportion of the N protein was detected in viral replication factories termed inclusion bodies (IBs). High-resolution analysis of the surface of M-null virus-infected cells by field emission scanning electron microscopy (SEM) revealed the presence of large areas with densely packed, uniformly short filaments. Although unusually short, these filaments were otherwise similar to those induced by an M-containing control virus, including the presence of the viral G and F proteins. The abundance of the short, stunted filaments in the absence of M indicates that M is not required for the initial stages of filament formation but plays an important role in the maturation or elongation of these structures. In addition, the absence of mature viral filaments and the simultaneous increase in the level of the N protein within IBs suggest that the M protein is involved in the transport of viral ribonucleoprotein (RNP) complexes from cytoplasmic IBs to sites of budding.

Effect of a dietary portfolio of cholesterol-lowering foods given at 2 levels of intensity of dietary advice on serum lipids in hyperlipidemia: a randomized controlled trial.

CONTEXT: Combining foods with recognized cholesterol-lowering properties (dietary portfolio) has proven highly effective in lowering serum cholesterol under metabolically controlled conditions. OBJECTIVE: To assess the effect of a dietary portfolio administered at 2 levels of intensity on percentage change in low-density lipoprotein cholesterol (LDL-C) among participants following self-selected diets. DESIGN, SETTING, AND PARTICIPANTS: A parallel-design study of 351 participants with hyperlipidemia from 4 participating academic centers across Canada (Quebec City, Toronto, Winnipeg, and Vancouver) randomized between June 25, 2007, and February 19, 2009, to 1 of 3 treatments lasting 6 months. INTERVENTION: Participants received dietary advice for 6 months on either a low-saturated fat therapeutic diet (control) or a dietary portfolio, for which counseling was delivered at different frequencies, that emphasized dietary incorporation of plant sterols, soy protein, viscous fibers, and nuts. Routine dietary portfolio involved 2 clinic visits over 6 months and intensive dietary portfolio involved 7 clinic visits over 6 months. MAIN OUTCOME MEASURES: Percentage change in serum LDL-C. RESULTS: In the modified intention-to-treat analysis of 345 participants, the overall attrition rate was not significantly different between treatments (18% for intensive dietary portfolio, 23% for routine dietary portfolio, and 26% for control; Fisher exact test, P = .33). The LDL-C reductions from an overall mean of 171 mg/dL (95% confidence interval [CI], 168-174 mg/dL) were -13.8% (95% CI, -17.2% to -10.3%; P < .001) or -26 mg/dL (95% CI, -31 to -21 mg/dL; P < .001) for the intensive dietary portfolio; -13.1% (95% CI, -16.7% to -9.5%; P < .001) or -24 mg/dL (95% CI, -30 to -19 mg/dL; P < .001) for the routine dietary portfolio; and -3.0% (95% CI, -6.1% to 0.1%; P = .06) or -8 mg/dL (95% CI, -13 to -3 mg/dL; P = .002) for the control diet. Percentage LDL-C reductions for each dietary portfolio were significantly more than the control diet (P < .001, respectively). The 2 dietary portfolio interventions did not differ significantly (P = .66). Among participants randomized to one of the dietary portfolio interventions, percentage reduction in LDL-C on the dietary portfolio was associated with dietary adherence (r = -0.34, n = 157, P < .001). CONCLUSION: Use of a dietary portfolio compared with the low-saturated fat dietary advice resulted in greater LDL-C lowering during 6 months of follow-up. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00438425.

Formulation and Evaluation of Propranolol Hydrochloride-Loaded Carbopol-934P/Ethyl Cellulose Mucoadhesive Microspheres.

The purpose of this research was to formulate and systemically evaluate in-vitro and in-vivo performances of mucoadhesive propranolol hydrochloride microspheres for its potential use in the treatment of hypertension, myocardial infraction and cardiac arrhythmias. Propranolol hydrochloride mucoadhesive microspheres, containing carbopol-934P as mucoadhesive polymer and ethyl cellulose as carrier polymer, were prepared by an emulsion-solvent evaporation technique. Results of preliminary trials indicated that the quantity of emulsifying agent, time for stirring, drug-to-polymers ratio, and speed of rotation affected various characteristics of microspheres. Microspheres were discrete, spherical, free-flowing and showed a good percentage of drug entrapment efficiency. An in-vitro mucoadhesive test showed that propranolol hydrochloride mucoadhesive microspheres adhered more strongly to the gastric mucous layer and could be retained in the gastrointestinal tract for an extended period of time. A 3(2) full factorial design was employed to study the effect of independent variables, drug-to-polymer-to-polymer ratio (propranolol hydrochloride-ethyl cellulose-carbopol-934P) (X 1), and stirring speed (X 2) on dependent variables, i.e. percentage of mucoadhesion, drug entrapment efficiency, particle size and t80. The best batch exhibited a high drug entrapment efficiency of 54 %; 82% mucoadhesion after 1 h and particle size of 110 µm. A sustained pattern of drug release was obtained for more than 12 h. The drug-to-polymer-to-polymer ratio had a more significant effect on the dependent variables. The morphological characteristics of the mucoadhesive microspheres were studied under a scanning electron microscope. In-vivo evaluation studies on propranolol hydrochloride mucoadhesive microspheres and propranolol hydrochloride powder were performed on normal healthy rabbits. The results showed a sustained anti-hypertensive effect over a longer period of time in case of mucoadhesive microspheres, compared to the powder. In conclusion, the prolonged gastrointestinal residence time and slow release of propranolol hydrochloride resulting from the mucoadhesive microspheres, could contribute to the provision of a sustained anti-hypertensive effect.

Key developmental transitions in human germinal center B cells are revealed by differential CD45RB expression.

We previously reported that RO(+) expression correlated with increased mutation, activation, and selection among human germinal center (GC) B cells. Here, we subdivided human tonsillar B cells, including IgD(-)CD38(+) GC B cells, into different fractions based on RB expression. Although each subset contained RB(+) cells, when used as an intrasubset marker, differential RB expression effectively discriminated between phenotypically distinct cells. For example, RB(+) GC B cells were enriched for activated cells with lower AID expression. RB inversely correlated with mutation frequency, demonstrating a key difference between RB- and RO-expressing GC B cells. Reduced RB expression during the transition from pre-GC (IgM(+)IgD(+)CD38(+)CD27(-)) to GCB cells was followed by a dramatic increase during the GC-to-plasmablast (IgD(-)CD38(++)CD27(+)) and memory (IgD(-)CD38(-)CD27(+)) transition. Interestingly, RB(+) GC B cells showed increased signs of terminal differentiation toward CD27(+) post-GC early plasmablast (increased CD38 and RO) or early memory (decreased CD38 and RO) B cells. We propose that as in T cells, differential RB expression directly correlates with development- and function-based transitions in tonsillar B cells. Application of this RB:RO system should advance our understanding of normal B-cell development and facilitate the isolation of more discrete B-cell populations with potentially different propensities in disease pathogenesis.

The effect of strawberries in a cholesterol-lowering dietary portfolio.

Effective diets reduce blood lipids and oxidative damage, both of which have been linked to the complications of diabetes and coronary heart disease. Our objective was to assess the effect of adding strawberries, as a source of antioxidants, to improve the antioxidant effect of a cholesterol-lowering diet (dietary portfolio). To this end, 28 hyperlipidemic subjects who had followed the dietary portfolio consisting of soy, viscous fiber, plant sterol, and nuts for a mean of 2.5 years were randomized to receive supplements of strawberries (454 g/d, 112 kcal) or additional oat bran bread (65 g/d, 112 kcal, approximately 2 g beta-glucan) (control) in a randomized 1-month crossover study with a 2-week washout. Strawberry supplementation resulted in a greater reduction in oxidative damage to low-density lipoprotein (LDL) measured as thiobarbituric acid-reactive substances in the LDL fraction (P = .014). At the end of the strawberry period, reductions in LDL cholesterol and in the ratio of total to high-density lipoprotein cholesterol were maintained close to 1-year values at -13.4% +/- 2.1% and -15.2% +/- 1.7%, respectively (P < .001), and were similar to the post-oat bran bread values. Strawberries also improved the palatability of the diet. We conclude that strawberry supplementation reduced oxidative damage to LDL while maintaining reductions in blood lipids and enhancing diet palatability. Added fruit may improve the overall utility of diets designed to lower coronary heart disease risk.

CD45RO enriches for activated, highly mutated human germinal center B cells.

To date, there is no consensus regarding the influence of different CD45 isoforms during peripheral B-cell development. Examining correlations between surface CD45RO expression and various physiologic processes ongoing during the germinal center (GC) reaction, we hypothesized that GC B cells, like T cells, that up-regulate surface RO should progressively acquire phenotypes commonly associated with activated, differentiating lymphocytes. GC B cells (IgD(-)CD38(+)) were subdivided into 3 surface CD45RO fractions: RO(-), RO(+/-), and RO(+). We show here that the average number of mutations per IgV(H) transcript increased in direct correlation with surface RO levels. Conjunctional use of RO and CD69 further delineated low/moderately and highly mutated fractions. Activation-induced cytidine deaminase (AID) mRNA was slightly reduced among RO(+) GC B cells, suggesting that higher mutation averages are unlikely due to elevated somatic mutation activity. Instead, RO(+) GC B cells were negative for Annexin V, comprised mostly (93%) of CD77(-) centrocytes, and were enriched for CD69(+) cells. Collectively, RO(+) GC B cells occupy what seems to be a specialized niche comprised mostly of centrocytes that may be in transition between activation states. These findings are among the first to sort GC B cells into populations enriched for live mutated cells solely using a single extracellular marker.