Aloe vera affects changes induced in pulmonary tissue of mice caused by cigarette smoke inhalation

This study was undertaken to determine the influence of Aloe vera (AV) on changes induced in pulmonary tissue of cigarette smoke (CS) inhaling mice. CS inhalation for 4 weeks caused pulmonary damage as evident by histoarchitectural alterations and enhanced serum and tissue lactate dehydrogenase (LDH) activities. CS inhalation also led to increased mucin production as revealed by mucicarmine and Alcian Blue‐Periodic Acid Schiff (AB‐PAS) staining. Studies on bronchoalveolar lavage fluid (balf) of CS exposed animals revealed structural changes in phospholipids and increase in surface tension when compared with control counterparts. These changes were accompanied by enhanced nitric oxide (NO) levels, citrulline levels, peroxidative damage, and differential modulation of antioxidant defense system. AV administration (seven weeks, 500 mg/kg b.w. daily) to CS inhaling mice led to modulation of CS induced pulmonary changes as revealed by lesser degree of histoarchitectural alterations, lesser mucin production, decreased NO levels, citrulline levels, peroxidative damage, and serum LDH activity. AV treatment to CS inhaling mice was associated with varying response to antioxidant defense system, however balf of CS + AV treated animals did not exhibit appreciable changes when compared with that of CS exposed animals. These observations suggest that AV has the potential to modulate CS induced changes in the pulmonary tissue which could have implications in management of CS associated pulmonary diseases, however, further investigations are required to explore its complete mechanism of action. © 2014 Wiley Periodicals, Inc. Environ Toxicol 30: 999–1013, 2015.     

Leptin and total cholesterol are predictors of weight gain in pre-pubertal children

OBJECTIVE: The aim of this study was to identify specifically which biochemical indices predict excessive weight gain over time in a cohort of pre-pubertal children. SUBJECTS: Fifty nine healthy pre-pubertal children (age: 6.3-9.8y). MEASUREMENTS: Children were defined anthropometrically and biochemically at baseline. Height and weight measurements were then repeated after six (n=52) and 12 months (n=37). RESULTS: Weight change after six months (defined by a change in body mass index (BMI) z-score from baseline) demonstrated no correlation with fasting plasma levels of leptin, insulin, insulin:glucose (IG) ratio, cholesterol, triglyceride or high density lipoprotein (HDL) cholesterol. However, after 12 months there was a significant negative correlation between BMI z-score change and initial plasma leptin (r=-0.35, P=0.048) and this relationship strengthened when adjusted for body fat (from bio-electrical impedance; r=-0.46, P=0.009). In addition, there was a significant positive relationship between plasma total cholesterol and BMI z score change (r=0.38, P=0.03) and this relationship remained unchanged when adjusted for body fat. No relationship was observed between weight change after 12 months and plasma levels of insulin, IG ratio, HDL cholesterol or triglyceride. CONCLUSION: Plasma leptin and total cholesterol were found to be predictive of weight gain over 12 months in a cohort of pre-pubertal children. These two potential predictors can be readily measured in clinical practice and these findings may represent a method of defining the 'at risk of obesity' state in childhood.     

Correlation of Ki-67, p53, and Adnab-9 immunohistochemical staining and ploidy with clinical and histopathologic features of severely dysplastic colorectal adenomas

Variations of Ki-67, p53, and Adnab-9 monoclonal antibody reactions in colonic adenomas may be associated with colonic cancer risk. We studied the predictive value of these markers for adverse behavior in severely dysplastic colorectal adenomas, such as an associated carcinoma, multiplicity of adenomas, and subsequent development of adenomas. For this purpose we compared the clinical, gross, and histologic characteristics of highly dysplastic index polyps in 42 patients with Ki 67, p53, and Adnab-9 immunostaining and other molecular markers. Polyps were removed endoscopically, and severely dysplastic polyps were stained immunohistochemically with Ki-67, Adnab-9, and p53 protein by the avidin biotin conjugate (ABC) technique. Quantitative DNA (QDNA) was analyzed by computer-assisted image analysis. Ki-67 immunohistochemistry showed reversal of normal distribution of nuclear staining from the normal basal position to the upper third of the colonic crypts. This abnormality of immunostaining in dysplastic adenomas was the earliest detected by the panel we used. A statistically significant correlation was seen between invasiveness of carcinoma in the index polyp and polyp size (P = 0.003), sessile morphology (P = 0.037), and villous or tubulovillous histology (P = 0.019). In the index adenoma, p53 positivity was correlated with multiplicity at initial examination (P = 0.053), villous histology (P = 0.053), invasiveness of carcinoma (P < 0.003), and recurrence of colorectal adenomas (P = 0.025). Although p53 positivity and aneuploidy were correlated with invasiveness of carcinoma in the index polyp (P = 0.025), Adnab-9 positivity was not. However, Adnab-9 positivity in the index polyp was associated with multiplicity of adenomas (P = 0.04) as well as recurrence of adenomas (P < 0.024). In conclusion, in addition to the morphologic and histologic markers already known, Ki-67, Adnab-9 antibody, and p53 protein may be prognostic indicators useful in follow-up of patients with severely dysplastic colorectal adenomas. Adnab-9 antibody may identify a field defect in above-average-risk adenoma-bearing patients.     

Effect of Vagotomy on Serum Gastrin in Patients with Duodenal Ulceration

The concept of increased vagal activity in patients with duodenal ulceration was investigated by observing the effect of medical and surgical vagotomy on the secretion of gastrin. Using a radioimmunoassay technique fasting serum levels of gastrin were determined in 41 normal subjects, 40 patients with duodenal ulceration and 16 patients following vagotomy. The effect of atropine on gastrin secretion was observed in a further 2 patients with duodenal ulceration. The patients with duodenal ulceration were found to have elevated serum levels of gastrin. The 8 patients with “complete” vagotomy had significantly lower serum levels of gastrin than the patients with duodenal ulceration, the patients with an “incomplete” vagotomy or the normal subjects. Post-vagotomy hypergastrinaemia was associated with a recurrence of ulceration. The abolition, by medical or surgical vagotomy, of the hypergastrinaemia associated with duodenal ulceration is consistent with the hypothesis of an increased vagal tone in this disease. These studies also suggest that gastrin estimations may be useful in predicting the presence of inadequate vagotomies.     

Genetic activation of pyruvate dehydrogenase alters oxidative substrate selection to induce skeletal muscle insulin resistance

The pyruvate dehydrogenase complex (PDH) has been hypothesized to link lipid exposure to skeletal muscle insulin resistance through a glucose-fatty acid cycle in which increased fatty acid oxidation increases acetyl-CoA concentrations, thereby inactivating PDH and decreasing glucose oxidation. However, whether fatty acids induce insulin resistance by decreasing PDH flux remains unknown. To genetically examine this hypothesis we assessed relative rates of pyruvate dehydrogenase flux/mitochondrial oxidative flux and insulin-stimulated rates of muscle glucose metabolism in awake mice lacking pyruvate dehydrogenase kinase 2 and 4 [double knockout (DKO)], which results in constitutively activated PDH. Surprisingly, increased glucose oxidation in DKO muscle was accompanied by reduced insulin-stimulated muscle glucose uptake. Preferential myocellular glucose utilization in DKO mice decreased fatty acid oxidation, resulting in increased reesterification of acyl-CoAs into diacylglycerol and triacylglycerol, with subsequent activation of PKC-θ and inhibition of insulin signaling in muscle. In contrast, other putative mediators of muscle insulin resistance, including muscle acylcarnitines, ceramides, reactive oxygen species production, and oxidative stress markers, were not increased. These findings demonstrate that modulation of oxidative substrate selection to increase muscle glucose utilization surprisingly results in muscle insulin resistance, offering genetic evidence against the glucose-fatty acid cycle hypothesis of muscle insulin resistance.Lipid-induced muscle insulin resistance plays a major role in the pathogenesis of type 2 diabetes (T2D), but the cellular mechanisms remain unknown (1, 2). More than 50 y ago Randle et al. (3) postulated the glucose-fatty acid cycle to explain the impairment of insulin-stimulated glucose disposal by fatty acids in muscle. In this model, fat oxidation increases mitochondrial acetyl-CoA/CoA and NADH/NAD⁺ ratios. Acetyl-CoA and NADH allosterically inhibit pyruvate dehydrogenase complex (PDH), the mitochondrial enzyme that links glycolysis to the TCA cycle by converting pyruvate to acetyl-CoA. Additionally, fatty acid-derived acetyl-CoA produces citrate, which inhibits phosphofructokinase. This in turn increases glucose-6-phosphate (G6P), a potent allosteric inhibitor of hexokinase. By these mechanisms, increased fatty acid oxidation was hypothesized to reduce glycolytic flux and prevent further muscle glucose uptake. However, in vivo studies of human skeletal muscle metabolism have challenged the Randle hypothesis. Five hours of a lipid infusion, combined with heparin to activate lipoprotein lipase, raised plasma fatty acids and induced muscle insulin resistance in healthy individuals, yet intramyocellular G6P and glucose concentrations were reduced compared with control glycerol infusion studies, implicating defects in insulin-stimulated glucose transport activity (4, 5). An alternative hypothesis to explain the muscle insulin resistance associated with lipid exposure posits that accumulation of bioactive lipid intermediates initiates signaling cascades that impair insulin action. Lipid species implicated include diacylglycerols (DAGs) (6–10), ceramides (11, 12), and long-chain acyl-CoAs (13). DAG activation of PKC-θ in skeletal muscle has been shown to impair canonical insulin signaling at the level of insulin receptor substrate-1 (IRS-1) tyrosine phosphorylation through increased IRS-1 serine phosphorylation at the 1101 position (2, 6, 7, 14).More recently, incomplete fat oxidation and subsequent accumulation of mitochondrially derived acylcarnitines has been proposed to contribute to lipid-induced muscle insulin resistance (15–17). According to this model, insulin resistance stems from increased fat oxidation, leading to increased conversion of acyl-CoA to medium- and long-chain acylcarnitines, which may mediate insulin resistance via unknown mechanisms. In contrast, short-chain acylcarnitines have been suggested to promote metabolic flexibility. The shortest acylcarnitine, acetylcarnitine, is synthesized from acetyl-CoA and carnitine by carnitine acetyltransferase (CrAT), a mitochondrial matrix enzyme, and is responsible for buffering the mitochondrial acetyl-CoA pool and mitigating acetyl-CoA inhibition of PDH (18). Consistent with the notion that CrAT regulates substrate selection by modulating PDH flux, mice with muscle-specific deletion of CrAT exhibited reduced PDH activity during the fed-to-fasted transition, resulting in glucose intolerance and metabolic inflexibility, a term coined by Kelley and Mandarino (19) to explain the impairment in the ability to adjust fuel oxidation to fuel availability.Although these studies emphasize the importance of PDH in the promotion of metabolic inflexibility, the role of PDH and mitochondrial oxidative substrate selection in the regulation of basal and insulin-stimulated muscle glucose metabolism has not been directly assessed in vivo. To examine this question, we sought to determine whether modulation of oxidative substrate selection in a genetic mouse model with constitutively active PDH activity would affect insulin sensitivity in skeletal muscle.     

Hyperlipidemia,tissue factor,coagulation, and simvastatin

Hyperlipidemia affects millions of people worldwide and is a major risk factor for cardiovascular disease. People with hyperlipidemia have elevated levels of serum cholesterol and an increased risk of thrombosis. Studies have suggested that oxidized lipoproteins, such as oxidized low-density lipoprotein (oxLDL), contribute to the development of a pro-thrombotic state. In this review, we discuss our recent studies demonstrating a role for hematopoietic cell-derived tissue factor (TF) expression in the activation of coagulation and increased thrombosis associated with hyperlipidemia. In addition, we investigated the effect of simvastatin on TF expression and coagulation. We found that simvastatin reduced leukocyte TF expression, TF⁺ microparticles, and coagulation. These results and earlier studies suggest that the anti-coagulant activity of statins is due, in part, to their ability to reduce monocyte TF expression in patients with cardiovascular disease.     

Marginal bone loss adjacent to conventional and immediate loaded two implants supporting a ball-retained mandibular overdenture: a 3-year randomized clinical trial

Objectives: The aim of this study was to evaluate and compare marginal bone loss and clinical outcomes of conventionally and immediately loaded two implants supporting a ball‐retained mandibular overdenture. Materials and methods: Thirty six completely edentulous patients (22 males and 14 females) were randomly assigned into two groups. Each patient received two implants in the canine area of the mandible after a minimal flap reflection. Implants were loaded by mandibular overdentures either 3 months (conventional loading group) or the same day (immediate loading group) after implant placement. Ball attachments were used to retain all overdentures to the implants. Vertical and horizontal alveolar bone losses were evaluated in both groups 1 and 3 years after implant placement using multislice computed tomography, which allow evaluation of peri‐implant buccal and lingual alveolar bone. Plaque scores, gingival scores, probing depths and periotest values (PTVs) were evaluated at 4 months (baseline), 1 and 3 years after implant placement. Clinical and radiographic evaluations were performed at distal, labial, mesial and lingual peri‐implant sites. Results: After 3 years of follow‐up period, the immediate loading group recorded significant vertical bone loss at distal and labial sites than the conventional loading group and no significant differences in horizontal bone loss between groups were observed. Probing depth at distal and labial sites in the immediate loading group were higher than the conventional loading group, while plaque scores, gingival scores and PTVs showed no significant differences between the two groups. A low level of positive correlation between plaque scores, gingival scores, probing depths and vertical bone loss was noted. Conclusion: Immediately loaded two implants supporting a ball‐retained mandibular overdenture are associated with more marginal bone resorption and increased probing depths when compared with conventionally loaded implants after 3 years. The bone resorption and probing depths at distal and labial sites are significantly higher than those at mesial and lingual sites. Clinical outcomes do not differ significantly between loading protocols. To cite this article :
Elsyad MA, Al‐Mahdy YF, Fouad MM. Marginal bone loss adjacent to conventional and immediate loaded two implants supporting a ball‐retained mandibular overdenture: a 3‐year randomized clinical trial.
Clin. Oral Impl. Res. 23 , 23, 2012 496‐503.
doi: 10.1111/j.1600‐0501.2011.02173.x