Relationship between salivary haemoglobin and number of remaining teeth in older Koreans

Objective

We investigated the relationship between saliva and dental biofilm characteristics, oral hygiene behaviours and the number of remaining teeth in a sample of older Koreans.

Materials and methods

This cross‐sectional study included 133 participants, aged 65 years and older, recruited from senior welfare facilities in Incheon, South Korea. The outcome variable was the number of remaining teeth, and its associations with the independent variables of participants’ general characteristics, salivary haemoglobin level, dental biofilm acidogenicity, salivary flow rate and oral hygiene behaviours were assessed. For statistical analyses, chi‐squared test and step‐wise multiple linear regression were used.

Results

The multiple linear regression model, which included all related factors identified in the bivariate analyses, showed that older adults who had high salivary haemoglobin levels (P < .05), brushed their teeth using the horizontal scrub method (P< .001), and did not use an interproximal cleaning device (P < .01) were more likely to have fewer remaining teeth. However, dental biofilm acidogenicity was not associated with the number of remaining teeth.

Conclusion

The number of remaining teeth was associated with salivary haemoglobin level, appropriate toothbrushing technique and interdental cleaning. These findings suggest that the monitoring of salivary haemoglobin may contribute to the prevention of tooth loss caused by periodontal disease.     

The investigation of genetic polymorphisms in the carbonic anhydrase VI gene exon 2 and salivary parameters in type 2 diabetic patients and healthy adults

The aim of this study was to investigate carbonic anhydrase (CA) VI Exon 2 single nucleotide polymorphism (SNP) and its possible association with salivary parameters in type 2 diabetic patients compared to healthy adults. Caries status was measured by using the DMFT (number of decayed, missing, and filled teeth) index. Unstimulated whole saliva and blood samples were taken. SNPs of CA gene exon 2 were determined by PCR and DNA sequencing. Salivary CA activity and buffering capacity were determined by the method of Verpoorte and Ericson, respectively. Furthermore, salivary pH was measured with pH paper and salivary flow rate was calculated. Salivary buffering capacity and pH were significantly lower in diabetic patients than those of healthy subjects (P < 0.05). Salivary flow rate, CA activity and DMFT levels did not differ between groups (P > 0.05). Four SNPs were detected; their pubmed database number are rs2274327 (C/T), rs2274328 (A/C), rs2274329 (G/C) and rs2274330. While first three of those were responsible for amino acid changes, the last one was not. The frequencies of SNPs were not significant between groups (P > 0.05). Positive significant correlation was found between CA activity and the frequency of SNPs. There was no correlation between the SNPs frequencies and pH or buffering capacity. SNPs found in this study may be related to salivary CA activity in diabetics.     

Sitagliptin therapy enhances the number of circulating angiogenic cells and angiogenesis—evaluations in vitro and in the rat critical limb ischemia model

Background aimsWe tested the hypothesis that sitagliptin is capable of increasing blood flow in the rat critical limb ischemia (CLI) model by enhancement of angiogenesis.MethodsAdipose tissue from adult-male Fischer 344 rats (n = 6) were cultured in endothelial progenitor cell culture medium for 14 d with (25 μmol/L) or without sitagliptin. CLI was induced by ligation of the left femoral artery. Rats (n = 32) were equally separated into four groups: untreated controls (group 1), sitagliptin (4 mg/kg per day; group 2), CLI (group 3) and CLI with sitagliptin (group 4).ResultsIn vitro, 7 and 14 d after cell culture, endothelial progenitor cell biomarkers assessed by flow cytometry (Sca-1/CD31+, CXCR4+, c-kit+ and CD34+ cells) and Western blot (vascular endothelial growth factor, CXCR4 and stromal-derived factor [SDF]-1α) were remarkably higher in group 4 than in the other groups (all P < 0.01). In vivo, 2 and 14 d after the CLI procedure, circulating angiogenic cell (Sca-1/CD31+, Sca-1+ and CD31+) numbers were significantly higher in group 4 than in the other groups (all P < 0.001). Additionally, the messenger RNA and protein expression of angiogenic biomarkers (CXCR4, SDF-1α and vascular endothelial growth factor), immunofluorescent staining of angiogenic cells (CXCR4+, SDF-1α+, CD31+, von Willebrand factor + cells) and immunohistochemical staining of small vessel numbers in the ischemic area were significantly higher in group 4 than in the other groups (all P < 0.01). Furthermore, laser Doppler showed that the ratio of ischemic/normal blood flow was remarkably higher group 4 than in group 3 by days 14 and 28 after the CLI procedure (all P < 0.01).ConclusionsSitagliptin therapy enhances circulating angiogenic cell numbers, angiogenesis and blood flow in the CLI area.     

Viability and engraftment of hematopoietic progenitor cells after long-term cryopreservation: effect of diagnosis and percentage dimethyl sulfoxide concentration

Background aimsWe carried out a retrospective analysis of viability by diagnosis and dimethyl sulfoxide (DMSO) concentration in patients who had undergone autologous transplants using hematopoietic progenitor cells (HPC) after long-term storage (up to 17.8 years).MethodsViability was tested using flow cytometry for HPC that were harvested and preserved using a controlled rate freezer and 5% or 10% DMSO with human serum albumin, then stored in liquid nitrogen. Data from 262 samples were analyzed (249 myeloma patients and 13 other diagnoses): 100 consecutively thawed samples with a storage time of <1 year (all 10% DMSO), 50 consecutive samples stored for 1–4.9 years (10% DMSO), 50 samples stored for 5–9 years (5% DMSO) and all samples stored and used for transplant after >9 years (60 samples, 5% DMSO; two samples, 10% DMSO).ResultsNo statistically significant difference in viability between the 5% DMSO and 10% DMSO groups was observed (P = 0.08), so the 1–4.9 years and 5–9 years were combined and the three groups (<1 year, 1–9 years and >9 years) were compared using an anova test. There was no difference in viability based on cryostorage period (P = 0.23) or between myeloma and other diagnoses (P = 0.45). No difference was seen in time to White blood cell (WBC) engraftment (P = 0.10) or to platelet engraftment between groups (P = 0.52).ConclusionsThese data suggest that long-term storage in 5% DMSO and human serum albumin is safe.     

The effects of saliva collection,handling and storage on salivary testosterone measurement

Several endocrine parameters commonly measured in plasma, such as steroid hormones, can be measured in the oral fluid. However, there are several technical aspects of saliva sampling and processing that can potentially bias the validity of salivary testosterone measurement. The aim of this study was to evaluate the effects caused by repeated sampling; 5 min centrifugation (at 2000, 6000 or 10,000g); the stimulation of saliva flow by a cotton swab soaked in 2% citric acid touching the tongue; different storage times and conditions as well as the impact of blood contamination on salivary testosterone concentration measured using a commercially available ELISA kit. Fresh, unprocessed, unstimulated saliva samples served as a control. Salivary testosterone concentrations were influenced neither by repeated sampling nor by stimulation of salivary flow. Testosterone levels determined in samples stored in various laboratory conditions for time periods up to 1 month did not differ in comparison with controls. For both genders, salivary testosterone levels were substantially reduced after centrifugation (men F = 29.1; women F = 56.17, p < 0.0001). Blood contamination decreased salivary testosterone levels in a dose-dependent manner (men F = 6.54, p < 0.01, F = 5.01, p < 0.05). Salivary testosterone can be considered A robust and stable marker. However, saliva processing and blood leakage can introduce bias into measurements of salivary testoterone using ELISA. Our observations should be considered in studies focusing on salivary testosterone.     

Salivary DNA,lipid, and protein oxidation in nonsmokers with periodontal disease

Reactive oxygen species (ROS) are implicated in the destruction of the periodontium during periodontitis. The imbalance in oxidant activity may be a key factor.The aim of this paper is to determine whether periodontitis is associated with increased oxidative damage to DNA, lipids, and proteins and modification of total antioxidant capacity (TAC) in saliva. Saliva was collected from 58 periodontitis patients and 234 healthy controls, all nonsmokers. Periodontal disease status was characterized using the Community Periodontal Index of Treatment Needs (CPITN). Assays for 8-OHdG (ELISA), 8-epi-PGF2α (ELISA), and total protein carbonyls (ELISA), and oxy-blotting (Western)/mass spectrometry were performed to quantify oxidative damage to nucleic acids, lipids, total and individual proteins, respectively, in whole nonstimulated saliva. Salivary TAC was measured by inhibition of ABTS oxidation by metmyoglobin. We observed (i) significantly higher levels of 8-OHdG, 8-epi-PGF2α, and carbonylated proteins in saliva of periodontal patients as compared with controls (P = 0.0003, < 0.0001 and < 0.0001); (ii) 8-OHdG, 8-epi-PGF2α, and carbonylated proteins were independently negatively associated with CPITN (P = 0.004, 0.02, and < 0.0001); (iii) a positive correlation between salivary TAC and periodontal disease status in the study group (P < 0.0001); and (iv) specific oxidation of transferrin, human IgG1 heavy chain fragment, and salivary amylase in periodontitis. Periodontal disease is associated with increased oxidative modification of salivary DNA, lipids, and proteins. Augmented salivary total antioxidant capacity may represent an adaptive response to oxidative stress. Salivary amylase, transferrin, and human IgG1 heavy chain fragments are particularly prone to enhanced oxidation in periodontitis.     

Prognostic implications of ENE and LODDS in relation to lymph node-positive colorectal cancer location

BackgroundExtranodal extension (ENE) and log odds of positive lymph nodes (LODDS) are associated with the aggressiveness of both colon and rectal cancers. The current study evaluated the clinicopathological significance and the prognostic impact of ENE and LODDS in the colon and rectal patients independently.MethodsThe clinical and histological records of 389 colorectal cancer (CRC) patients who underwent curative surgery were reviewed.ResultsFor the ENE system, 244 patients were in the ENE1 group and 145 in the ENE2 system. Compared with the ENE1 system, the patients included in the ENE2 system were prone to nerve invasion (P < 0.001) and vessel invasion (P < 0.001) with higher TNM (P = 0.009), higher T category (P = 0.003), higher N category (P < 0.001), advanced differentiation (P = 0.013), more number of positive lymph nodes (NPLN) (P < 0.001), more lymph node ratio (LNR) (P < 0.001), and a higher value of LODDS (P < 0.001). ENE was more frequent in patients with left and rectal than right cancer. For the LODDS system, 280 patients were in the LODDS1 group, and 109 in the LODDS2 group. Compared to the LODDS1 group, the patients included in the LODDS2 group were more prone to nerve invasion (P = 0.0351) and vessel invasion (P < 0.001) with a higher rate of N2 stage, less NDLN (P < 0.001), more NPLN (P < 0.001), more LNR (P < 0.001), and a higher value of ENE (P < 0.001). Based on the results in the univariable analysis, the N, NPLN, LNR, LODDS, and ENE were separately incorporated into five different Cox regression models combined with the same confounders. The multivariable Cox regression analysis demonstrated that all the five staging systems were independent prognostic factors for overall survival.ConclusionThe current study confirmed that the LODDS stage is an independent influence on the prognosis of both CRC and CC patients. ENE is an independent influencing factor on the prognosis of both CRC and CC patients, and the prognostic impact of extracapsular lymph node was observed in both CRC and CC. The frequency of ENE increases from the proximal (right) to the distal (left) colon as well as the rectum. Therefore, combining ENE and LODDS into the current TNM system to compensate for the inadequacy of pN staging needs further investigation.     

The effect of glucagon-like peptide-2 on arterial blood flow and cardiac parameters

BackgroundGlucagon-like peptide-2 (GLP-2) is known to increase mesenteric blood flow. The aim of the study was to evaluate the effect of GLP-2 on blood flow in different vascular sites, and dynamic changes in cardiac parameters.Methods10 healthy volunteers were given 450 nmol subcutaneous (SC) GLP-2 or isotonic saline (5 subjects) in a single blinded manner. During the following 90 min, blood flow in the superior mesenteric artery (SMA), celiac artery (CA), renal artery (RA), common carotid artery (CCA) was measured using Doppler ultrasound (US), and cardiovascular variables were measured by impedance cardiography and finger plethysmography. Plasma GLP-2 was measured at times 0, 30 and 60 min.ResultsCompared to the placebo group, GLP-2 elicited a 27% decrease in the resistance index (RI) and a 269.4% increase in Time Averaged Maximal Velocity (TAMV) in the SMA (P < 0.01). CA, RA and CCA: There were no significant changes in RI or TAMV in the GLP-2 or placebo group, and no change in CA diameter.Cardiac parameters: GLP-2 increased cardiac output (CO), stroke volume (SV) and heart rate (HR) compared to baseline (respectively: 15.3, 4.81 and 8.2% (P < 0.001, P < 0.01 and P < 0.01)). The CO, SV and HR changes were not significantly different from the placebo group.Mean plasma GLP-2 serum levels in the placebo group at times 0, 30 and 60 min were 22.8, 23.4 and 23.2 pmol/l. In the GLP-2 group 20.3, 1273 and 1725 pmol/l.ConclusionSC GLP-2 increased SMA blood flow, as previously shown, but elicited no changes in other vascular sites. CO and HR increased significantly, presumably due to the increased mesenteric blood flow.     

Salivary Nickel and Chromium Levels in Orthodontic Patients with and Without Periodontitis: a Preliminary Historical Cohort Study

Many periodontal patients may need orthodontic treatment. Alterations in oral environment particularly the reduction of pH in periodontal patients could affect metal ion release from orthodontic appliances. However, there is no study on metal ion release in periodontal patients. The aim of this preliminary study was to comparatively evaluate, for the first time, salivary levels of nickel and chromium in periodontal patients (versus healthy controls) under orthodontic treatment for 2 months. In this in vivo study, 40 subjects were evaluated. Patient selection and standardization of orthodontic treatment protocols were prospectively designed and performed. Two groups of n = 20 each (control: healthy orthodontic patients, cohort: orthodontic patients with periodontitis) underwent similar protocols of fixed orthodontic treatment for 2 months. After 2 months, salivary nickel and chromium concentrations of the case and cohort groups were measured using inductively coupled plasma mass spectrometry (ICP-MS). The values were compared between the two groups using t test. There were 10 men and 10 women in each group. The mean age of patients was 34.6 ± 3.6 years old. The salivary level of nickel was 338.2 ± 235.5 ng/ml and 182.8 ± 116.5 ng/ml in the cohort and control groups, respectively (P = 0.0118). The salivary level of chromium was 7.4 ± 3.15 ng/ml in the cohort and 6.35 ± 2.39 ng/ml in the control group (P = 0.2214). Salivary level of nickel might be considerably higher in periodontal patients undergoing 2 months of orthodontic treatment compared to orthodontic patients with healthy gingivae.

     

Salivary detection of periodontopathic bacteria and periodontal health status in dental students

ObjectiveSaliva may become a potential source of contamination through vertical and horizontal transmissions as well as cross-infections. This study aims to use saliva as a screening tool to detect putative periodontal pathogens in a young population with fairly good oral hygiene.Materials and methodsStimulated saliva samples were obtained from 134 dental students (20.5 ± 1 years, range 18–22 years). Among those, 77 subjects also completed a periodontal examination including attachment loss, modified dental, gingival and plaque indices (AL, mDI, GI and PI). The test bacteria were identified using a 16S rRNA-based PCR detection method.ResultsOne or more of the test bacteria was found in 67% of the subjects. Prevotella nigrescens was detected as single bacterium in 16% of the subjects followed by Treponema denticola (4%), Porphyromonas gingivalis (2%), Aggregatibacter (formerly Actinobacillus) actinomycetemcomitans (1%) and Tannerella forsythia (1%). Two or more pathogens were detected in 42% of the subjects. Clinical examination revealed health with no attachment loss (AL) in 84% of the students. In no AL group, 38% of the students were pathogen free while this was 25% for students in localized AL group (p > 0.05). There was a statistically significant association between the detection of salivary periodontal pathogen in general and higher PI (p = 0.018) and GI (p = 0.043).ConclusionWithin the limits of this study, it is possible to detect all six periodontal pathogens in the saliva of dental students. Although a correlation can be observed between the presence of salivary periodontal pathogen and clinical signs of inflammation such as plaque accumulation and gingival bleeding, detection of specific bacteria in saliva is not related to the presence of localized AL based on the presented study population.     

Myoepithelial carcinoma of major salivary glands: Analysis of population-based clinicopathologic and prognostic features

BackgroundThis study aimed to investigate the effect of demographic characteristics and disease stage on the survival outcomes of patients with myoepithelial carcinoma (MECA) of the salivary glands, and to assess the role of radiotherapy in these patients.MethodsThe Epidemiology, Surveillance and End Results database was queried from 2000 to 2018 to identify patients with MECA. Data pertaining to the tumor stage, size, histological grade, and demographic characteristics were analyzed. The relationship between clinicopathological features and overall survival (OS) was assessed using statistical analyses.ResultsIn total, 290 patients (137 men and 153 women) were identified. The parotid gland was the most common tumor location (76.6% patients). Approximately half of the patients had locally advanced tumors, and 14.5 and 6.6% had lymph node and distant organ involvement, respectively. The median OS was 142 months, while the survival rates at 120 months and 180 months were 53% and 39%, respectively. In the cohort, 160 patients (55.2%) underwent surgery alone, while 130 patients (44.8%) underwent surgery combined with radiotherapy. Multivariate Cox analysis revealed that histopathological grade, stage, T3 stage (hazard ratio [HR]: 2.47, P = 0.039), T4 stage (HR: 3.33, P = 0.011), N2 stage (HR: 6.59, P = 0.002), and M1 stage (HR: 2.72, 95%confidence interval [CI]: 1.03–7.19; P = 0.044) were associated with poor prognosis. Radiotherapy (HR: 0.58, P = 0.042) was a favorable factor for OS, and it reduced the mortality risk by 42%.ConclusionsHistological grade, stage, and radiotherapy are independent risk factors for OS. The decision to administer chemotherapy for MECA should be made with caution. Adjuvant radiotherapy is recommended in high-risk patients.     

Diagnostic performance of salivary cortisol and serum osteocalcin measurements in patients with overt and subclinical Cushing's syndrome

ObjectiveThe cut-off value for salivary cortisol measurement for the diagnosis of Cushing's syndrome (CS) may depend both on the severity of the disease and the composition of control group. Therefore, we examined the utility of midnight salivary cortisol measurements in patients who were evaluated for signs and symptoms of CS or because they had adrenal incidentalomas. Because serum osteocalcin (OC) is considered as a sensitive marker of hypercortisolism, we also investigated whether OC could have a role in the diagnosis of CS.Patients and methodsEach of the 151 patients was included into one of the following groups: (A) overt CS (n = 23), (B) subclinical CS (n = 18), (C) inactive adrenal adenomas (n = 40), (D) patients without HPA disturbances (n = 70). Patients (C + D) were used as controls. Serum, salivary and urinary cortisol, and OC were measured by electrochemiluminescence immunoassay.ResultsGroup A had suppressed OC as compared to both group B and group (C + D). Serum and salivary cortisol concentrations showed strong negative correlations with OC in patients with overt CS. The areas under the curves of salivary and serum cortisol at 24:00 h (0.9790 and 0.9940, respectively) serum cortisol after low dose dexamethasone test (0.9930) and OC (0.9220) obtained from ROC aanalysis for the diagnosis of overt CS were not statistically different.ConclusionThis study confirms the usefulness of midnight salivary cortisol measurements in the diagnosis of overt CS in the everyday endocrinological praxis. Our results suggest that OC may have a role in the diagnosis of overt CS.     

Bone marrow-derived mesenchymal stromal cells improve vascular regeneration and reduce leukocyte-endothelium activation in critical ischemic murine skin in a dose-dependent manner

Background aimsStem cells participate in vascular regeneration following critical ischemia. However, their angiogenic and remodeling properties, as well as their role in ischemia-related endothelial leukocyte activation, need to be further elucidated. Herein, we investigated the effect of bone marrow–derived mesenchymal stromal cells (BM-MSCs) in a critically ischemic murine skin flap model.MethodsGroups received either 1 × 10⁵, 5 × 10⁵, or 1 × 10⁶ BM-MSCs or cell-free conditioned medium (CM). Controls received sodium chloride. Intravital fluorescence microscopy was performed for morphological and quantitative assessment of micro-hemodynamic parameters over 12 days.ResultsTortuosity and diameter of conduit-arterioles were pronounced in the MSC groups (P < 0.01), whereas vasodilation was shifted to the end arteriolar level in the CM group (P < 0.01). These effects were accompanied by angiopoietin-2 expression. Functional capillary density and red blood cell velocity were enhanced in all treatment groups (P < 0.01). Although a significant reduction of rolling and sticking leukocytes was observed in the MSC groups with a reduction of diameter in postcapillary venules (P < 0.01), animals receiving CM exhibited a leukocyte-endothelium interaction similar to controls. This correlated with leukocyte common antigen expression in tissue sections (P < 0.01) and p38 mitogen-activated protein kinase expression from tissue samples. Cytokine analysis from BM-MSC culture medium revealed a 50% reduction of pro-inflammatory cytokines (interleukin [IL]-1β, IL-6, IL-12, tumor necrosis factor-α, interferon-γ) and chemokines (keratinocyte chemoattractant, granulocyte colony-stimulating factor) under hypoxic conditions.DiscussionWe demonstrated positive effects of BM-MSCs on vascular regeneration and modulation of endothelial leukocyte adhesion in critical ischemic skin. The improvements after MSC application were dose-dependent and superior to the use of CM alone.     

Role of monocyte chemoattractant protein-1 (MCP-1) as an immune-diagnostic biomarker in the pathogenesis of chronic periodontal disease

ObjectiveMonocyte chemoattractant protein-1 (MCP-1) is an important chemokine responsible for the initiation, regulation and mobilization of monocytes to the active sites of severe periodontal inflammation. The present study aims at evaluating the levels of MCP-1 in GCF, saliva and serum and to analyze the changes following phase I periodontal therapy. Assessment of possible correlations between levels of MCP-1 in the three biological fluids was also done.MethodsFifteen healthy and 30 patients of severe chronic periodontitis (diseased) participated in the study. Patients of the diseased group underwent scaling/root planing. Evaluation of PI, GI, PD, CAL and collection of samples of GCF, serum and saliva was done at baseline and 6 weeks following periodontal therapy. MCP-1 levels were quantified in all samples using ELISA.ResultsCompared to healthy controls, MCP-1 levels were statistically significantly higher in GCF (p < 0.001), saliva (p = 0.002) and serum (p < 0.001) in subjects with chronic periodontitis. Levels of MCP-1 in all the three fluids decreased significantly in patients after periodontal therapy (p < 0.001). There was a significant positive correlation between MCP-1 levels in GCF, saliva and serum in patients of chronic periodontitis both pre (r > 0.9) and post-treatment (r > 0.6).ConclusionsThe results suggest that levels of MCP-1 in GCF and saliva can be reliable indicators of severity of periodontal destruction and their serum levels reflect the systemic impact of this local inflammatory disease thereby strengthening the reciprocal oro-systemic association.     

Upregulation of NKG2D ligands in acute lymphoblastic leukemia and non-Hodgkin lymphoma cells by romidepsin and enhanced in vitro and in vivo natural killer cell cytotoxicity

Background aimsThere is a critical need to prevent and/or treat hematological relapse after allogeneic hematopoietic stem cell transplantation. The activating NKG2D receptor expressed on natural killer (NK) cells, when engaged by its corresponding ligands (MIC A/B), activates NK cells to become cytotoxic against malignant cells.MethodsWe incubated acute lymphoblastic leukemia and non-Hodgkin lymphoma cells for 24 h with 10 ng/mL of romidepsin. Flow cytometry was performed to demonstrate changes in surface expression of NKG2D ligands MIC A/B. In vitro and in vivo cytotoxicity was measured by means of modified Europium assay, and non-obese diabetic/severe combined immunodeficiency mice were xenografted with RS 4:11 cells.ResultsWe demonstrated an approximately 50, 200, 1300 and 180-fold increase in the number of cells positive for the surface expression of MIC A/B in RS 4:11 (P < 0.001), REH (P < 0.001), Ramos (P < 0.001) and Jurkat cells (P < 0.001), respectively. We further demonstrated a significant increase in NK cell–mediated in vitro cytotoxicity against RS 4:11 (P < 0.004), Ramos (P < 0.05), Jurkat (P < 0.001) and REH cells (P < 0.01), respectively. Romidepsin-mediated NK cytotoxicity was blocked by pre-incubating NK cells with anti-NKG2D-Fc in RS 4:11 (P < 0.03) and Ramos cells (P < 0.01), respectively. Finally, non-obese diabetic/severe combined immunodeficiency mice xenografted with RS 4:11 cells had a significant increase in survival (P < 0.02) in mice treated with romidepsin and interleukin-2–activated NK cells compared with each of these other treatment groups.ConclusionsRomidepsin significantly enhanced in vitro and in vivo NK cell cytotoxicity mediated in part by increased MIC A/B expression on malignant cells. This translational approach of the use of romidepsin and interleukin-2–activated NK cells should be considered in patients with relapsed/refractory leukemia or lymphoma.     

Hyaluronate decorated polyethylene glycol linked poly(lactide-co-glycolide) nanoparticles encapsulating MUC-1 peptide augmented mucosal immune response in Balb/c mice through inhalation route

Background and objectivesNSCLC (Non-Small Cell Lung Cancer) clutches highest mortality rate in man and women globally. The present study was conducted to target MUC-1 peptide (M-1) into antigen presenting cells by cargo the peptide into hyaluronic acid decorated polyethylene glycol linked poly (D, l-lactide-co-glycolide) nanoparticles (M-1-PL-co-GA-PEG-sHA-NPs) for generating mucosal immunity through inhalation (i.h.) route.Methodology and resultsThe mean particle size and surface charge of M-1-PL-co-GA-PEG-sHA-NPs was measured to be 136.2 ± 18.38-nm and ? 28.34 ± 6.77-mV, respectively, prepared by non-aggregated emulsion-diffusion evaporation method. The 28.42% percentage release of M-1 peptide from M-1-PL-co-GA-PEG-NPs was observed to be at 2 h and 95.29% at 8 h while the percentage release of M-1 peptide from M-1-PL-co-GA-PEG-sHA-NPs was observed to be 26.02% at 4 h and 97.95% at 24 h that proved the prolonged release of antigen. M-1-PL-co-GA-PEG-sHA-NPs demonstrated higher (P < 0.05) cellular uptake of 86.2% in RAW 264.7 cells in comparison to 27.6% of M-1-PL-co-GA-PEG-NPs. In addition, M-1-PL-co-GA-PEG-sHA-NPs induced remarkably (P < 0.05) elevated release of 80.6-pg/ml of TNF-α in comparison to 5-pg/ml by culture medium and 57.9-pg/ml of TNF-α by M-1-PL-co-GA-PEG-NPs. Similarly, M-1-PL-co-GA-PEG-sHA-NPs persuade remarkably (P < 0.05) elevated release of 225-pg/ml of IL-1β in comparison to 47-pg/ml by culture medium and 161.9-pg/ml of IL-1β by M-1-PL-co-GA-PEG-NPs. M-1-PL-co-GA-PEG-sHA-NPs might have been endocytosed through receptor mediated pathway owing to presence of sHA. Mice immunized through i.h. route with M-1-PL-co-GA-PEG-sHA-NPs induced strong (P < 0.05) IgA antibody titre as compared to M-1-PL-co-GA-PEG-NPs and M-1 peptide in dose-dosage regimen.ConclusionM-1-PL-co-GA-PEG-sHA-NPs nanovaccine warrants further analysis in xenograft model of NSCLC to showcase its antitumor capability.     

Initial Combination Therapy with Metformin and Colesevelam for Achievement of Glycemic and Lipid Goals Min Early Type 2 Diabetes

ObjectiveTo evaluate the efficacy and safety of initial combination therapy with metformin plus colesevelam in patients with early type 2 diabetes.MethodsIn this 16-week, randomized, double-blind, placebo-controlled study, adults with type 2 diabetes (hemoglobin A1c [A1C] values of 6.5% to 10.0%) and hypercholesterolemia (low-density lipoprotein cholesterol [LDL-C] levels ≥ 100 mg/dL) were randomly assigned (1:1) to colesevelam (3.75 g/d) or placebo in combination with open-label metformin (850 mg/d; uptitrated at week 2 to 1, 700 mg/d). The primary efficacy evaluation was change in A1C from baseline to study end (week 16 with last observation carried forward).ResultsIn total, 286 patients were randomized: metformin/colesevelam (n = 145) or metformin/placebo (n = 141). Mean A1C was reduced by 1.1% with metformin/ colesevelam (from 7.8% at baseline to 6.6% at study end) and by 0.8% with metformin/placebo (from 7.5% to 6.7%), resulting in a treatment difference of -0.3% at study end (P = .0035). In addition, metformin/colesevelam significantly reduced LDL-C (-16.3%), total cholesterol (-6.1%), non-high-density lipoprotein cholesterol (-8.3%), apolipoprotein B (-8.0%), and high-sensitivity C-reactive protein (-17%) and increased apolipoprotein A-I (+ 4.4%) and triglycerides (+ 18.6%) versus metformin/placebo (P < .01 for all). The proportions of patients who achieved recommended goals with metformin/colesevelam versus metformin/placebo, respectively, were as follows: A1C < 7.0% (67% versus 56% [P = .0092]), LDL-C < 100 mg/dL (48% versus 18% [P < .0001]), and composite A1C < 7.0% + LDL-C < 100 mg/dL (40% versus 12% [P < .0001]). Safety and tolerability were similar between the treatment groups.ConclusionMetformin plus colesevelam may be a valid option for initial therapy to achieve glycemic and lipid goals safely in early type 2 diabetes. (Endocr Pract. 2010;16:629-640)     

Improved Glycemic Control with Insulin Glargine Versus Pioglitazone as Add-On Therapy to Sulfonylurea or Metformin in Patients with Uncontrolled Type 2 Diabetes Mellitus

ObjectiveTo compare glycemic control with add-on insulin glargine versus pioglitazone treatment in patients with type 2 diabetes.MethodsThis 48-week, multicenter, parallel-group, open-label study randomized 389 adults with poorly controlled type 2 diabetes (glycated hemoglobin A1c [A1C], 8.0% to 12.0%), despite ≥ 3 months of sulfonylurea or metformin monotherapy, to receive add-on therapy with insulin glargine or pioglitazone. Outcomes included A1C change from baseline to end point (primary), percentage of patients achieving A1C levels ≤ 7.0%, and changes from baseline in fasting plasma glucose, body mass index, weight, and serum lipids. The safety analysis included incidence of adverse events and rates of hypoglycemia.ResultsAt end point, insulin glargine yielded a significantly greater reduction in A1C in comparison with pioglitazone (-2.48% versus -1.86%, respectively; 95% confidence interval, -0.93 to -0.31; P = .0001, 48-week modified intent-to-treat population). Insulin glargine also yielded significantly greater reductions in fasting plasma glucose at all time points (end point difference, -34.9 mg/ dL; 95% confidence interval, -47.6 to -22.2; P < .0001). In comparison with pioglitazone, insulin glargine resulted in a lower overall incidence of possibly related treatmentemergent adverse events (12.0% versus 20.7%) and fewer study discontinuations (2.2% versus 9.1%), but a higher rate (per patient-year) of confirmed clinically relevant hypoglycemic episodes (blood glucose < 70 mg/dL and all severe hypoglycemia) (4.97 versus 1.04; P <.0001) and severe hypoglycemia (0.07 versus 0.01; P = .0309). Weight and body mass index changes were similar between the 2 treatment groups.ConclusionThe addition of insulin glargine early in the diabetes treatment paradigm in patients for whom sulfonylurea or metformin monotherapy had failed resulted in significantly greater improvements in glycemic control in comparison with the addition of pioglitazone. Although severe hypoglycemia was more frequent in patients with insulin glargine therapy, hypoglycemic events occurred in < 5% of patients in the insulin glargine treatment group. (Endocr Pract. 2010;16:588-599)     

Glucagon-like peptide-2 mobilization of intestinal lipid does not require canonical enterocyte chylomicron synthetic machinery

Background & aimsDietary triglycerides (TG) retained in the intestine after a meal can be mobilized many hours later by glucagon-like peptide-2 (GLP-2) in humans and animal models, despite the well-documented absence of expression of the GLP-2 receptor on enterocytes. In this study, we examined the site of GLP-2 action to mobilize intestinal lipids and enhance chylomicron production.MethodsIn mesenteric lymph duct-cannulated rats, we assessed GLP-2-stimulated lymph flow rate, TG concentration, TG output, and apoB48 abundance 5 h after an intraduodenal lipid bolus, in the presence of a validated GLP-2 antagonist or vehicle. Additionally, the same GLP-2-stimulated parameters were examined in the presence or absence of cis-Golgi disruption by Brefeldin A (BFA).ResultsCompared to placebo, GLP-2 administration increased lymph flow by 2.8-fold (P < 0.001), cumulative lymph volume by 2.69-fold (P < 0.001) and total TG output 2-fold (P = 0.015). GLP-2 receptor antagonism markedly diminished GLP-2's ability to stimulate lymph flow, cumulative lymph volume and total TG output, demonstrating the dependence of GLP-2 stimulation of lymph flow and TG output on its receptor activation. In contrast, disruption of the cis-Golgi apparatus with Brefeldin A did not diminish the GLP-2-response of lymph flow i.e., increased lymph flow by 2.7-fold (P = 0.001), lymph volume by 2.9-fold (P = 0.001), and total TG output i.e., increased by 2.5-fold (P = 0.003).ConclusionsGLP-2 mobilizes enteral lipid at a site distal to the Golgi, acting via its receptor. Since GLP-2 receptors are not expressed on enterocytes, GLP-2 likely mobilizes intestinal lipid residing extracellularly, either in the lamina propria or in the lymphatics.     

Effect of latanoprost on intraocular pressure,visual acuity and C-reactive protein

ObjectiveTo investigate the effect of latanoprost on intraocular pressure (IOP), visual acuity and C-reactive protein (CRP) in patients with primary open-angle glaucoma (POAG).MethodsA total of 163 POAG patients (266 eyes) admitted to our hospital from February 2015 to July 2017 were selected and divided into observation group (81 cases, 132 eyes, latanoprost eye drops) and control group (82 cases, 134 eyes, timolol maleate eye drops) according to different treatment plans. The clinical efficacy of the two groups after treatment was evaluated. The IOP, visual acuity and CRP level were compared between the two groups before and after treatment. Then the adverse reactions of the two groups were observed and recorded.ResultsAfter treatment, the total effective rate was 92.59% (75 cases) in the observation group and was 80.49% (66 cases) in the control group, with statistic difference between groups (P < 0.05); The IOP, visual acuity and CRP level between the two groups before treatment showed no statistic difference, the mentioned three indexes of the two groups were significantly improved after treatment, and statistic difference was found before and after treatment (P < 0.05); Moreover, the above three indicators had statistically significant differences between groups after treatment (P < 0.05); The difference of intraocular pressure and visual acuity between the two groups before and after treatment were statistically different (P < 0.05); After treatment, the incidence of adverse reactions in the observation group such as allergy, vomiting, breathlessness and tachycardia were not significantly different from those in the control group (P > 0.05).ConclusionLatanoprost can improve IOP, visual acuity, and CRP levels. It improves eye hemodynamics, and has significant efficacy in treating primary open-angle glaucoma. Also, it has good security.