Evaluation of Vitamin D-enriched Bone Graft in Surgically-induced Critical-sized Bone Defects: An Experimental Study.

BACKGROUND: Restoration of bone defects in the craniac vault may require the use of autografts, allografts, xenografts, or synthetic grafts. There are promising data that vitamin D may play a positive role in graft incorporation. The purpose of the present study is the evaluation of the impact of vitamin D addition to human-derived bone grafts in the healing of critical-sized bone defects in porcine skulls. MATERIALS AND METHODS: Four identical critical-sized defects were created in the calvaria of 8 adult Landrace Large White pigs. The first defect was left blank as control, the second defect was filled with human-derived bone graft, the third defect was filled with human-derived bone graft enriched with a low concentration of vitamin D (2 mg/mL), and the fourth defect was filled with human-derived bone graft enriched with a high concentration of vitamin D (10 mg/mL). The animals were sacrificed after 12 weeks. Harvested tissue specimens were qualitatively evaluated by histology. New bone formation (bone volume/tissue volume) was quantitatively measured by histomorphometry. RESULTS: Signs of bone formation were evident in all bone sockets. Mean values of the bone volume/tissue volume of the 4 defects were 10.91%, 11.05%, 10.40% and 10.87% respectively, at 12 weeks. In 5 animals, high concentration of vitamin D caused a significant improvement in bone formation in relation to controls. In 3 animals, a high concentration of vitamin D was associated with decreased bone formation compared with controls. No statistical difference was observed in the graft healing among the 4 graft sites ( P > 0.05). CONCLUSIONS: The results of this study have shown that the addition of vitamin D to human-derived bone grafts does not have a significant effect on bone formation and graft incorporation in critical-sized bone defects of the porcine calvaria. Further high-quality studies are needed to fully elucidate the role of vitamin D in bone formation and bone graft union.

Mechanisms and Therapeutic Approaches for Peritoneal Adhesions: A Comprehensive Review.

Peritoneal adhesions are responsible for several and sometimes severe clinical phenotypes remaining a major problem for many patients today. Adhesions are formed within the peritoneal cavity as a result of surgery, inflammation, or injury and can cause a range of clinical symptoms, including abdominal pain, small bowel obstruction, infertility, and other complications. The incidence of peritoneal adhesions remains high as it is estimated that more than 50% of patients who undergo abdominal surgery will develop adhesions. Although advancements in surgical techniques and perioperative management have been developed, the risk of adhesion formation cannot be eliminated, and thus, the development of effective prevention strategies and treatments remains a priority in the field of surgery. In this review, we summarize the cellular and molecular mechanisms involved in the peritoneal adhesions, but also the experimental therapy approaches that have been investigated toward a solution to their possible clinical phenotypes.

Platelet-Rich Plasma for Pleurodesis: An Experimental Study in Rabbits.

Background and Objectives: This study was designed to evaluate platelet-rich plasma (PRP) as a method of pleurodesis in a rabbit model. Pleurodesis with PRP was compared against the gold-standard use of talc. The secondary evaluation assessed the ideal time for achieving pleurodesis. Materials and Methods: 25 healthy New Zealand white rabbits were assigned to three groups, as follows: 12 animals in the first and second groups, as well as one animal with no intervention in the final group, which was used as a control. The talc pleurodesis group (baseline) underwent pleurodesis with sterile talc, which is the gold-standard sclerosing agent used for pleurodesis. The PRP group underwent pleurodesis using autologous PRP. The last group had one rabbit with no intervention. A total of 12 rabbits (n = 6 for the talc pleurodesis group and n = 6 for the PRP group) were sacrificed 3 days (72 h) after the intervention, and 12 rabbits (n = 6 for the talc pleurodesis group and n = 6 for the PRP group) were sacrificed 6 days (144 h) after the intervention. In both the talc and PRP group, FBC and CRP were measured before the intervention and in 3 or 6 days afterwards, respectively. The pleura and the lungs were evaluated histopathologically. Results: Macroscopically, there were no statistically significant differences between the two groups. In terms of microscopic findings, there were no statistically significant differences in inflammatory reactions provoked in the visceral and parietal pleura between the PRP and talc. In addition, with talc pleurodesis, a foreign-body reaction was observed in about 50% of the cases, which was not observed with PRP. In terms of inflammation between 3 and 6 days, there were no statistically significant differences with PRP, there was only a statistically significant difference between 3 and 6 days regarding the parietal pleura in the talc group. Conclusions: The instillation of autologous PRP in the pleural cavity shows promise in achieving pleurodesis. The efficacy of PRP as a pleurodesis agent should be examined further.

Platelet-rich Plasma Gel versus Hyaluronic Acid on Prevention of Peritoneal Abdominal Adhesion Formation in Rats.

Background: Intra-abdominal adhesion formation is still unavoidable and a cause of significant morbidity in abdominal surgery. Platelet-rich plasma gel and hyaluronic acid have been studied for their protective of therapeutic effects on adhesions. The aim of the present study is to compare Platelet-rich plasma and hyaluronic acid in adhesion prevention. Material and method: Twenty-seven Sprague-Dawley rats were randomly allocated into three equal groups(n=9). Surgical trauma was used to induce adhesion formation. After trauma, 1 ml normal saline was instilled in the peritoneal cavity in control group (n=9), 1 ml liquid Hyaluronic acid (25 mg/ml) was instilled in group A (n= 9) and 1 ml of platelet-rich plasma was instilled in group B (n = 9). Four weeks after the laparotomy, a repetitive laparotomy was performed and adhesions were examined microscopically and macroscopically. Results: Platelet-rich plasma gel and hyaluronic acid both reduce the extent and grade of adhesions macroscopically. Interestingly, PRP turns out to be superior in the reduction of tenacity and adhesion area. Moreover, platelet-rich plasma ameliorates abdominal adhesion formation by reducing neutrophils, fibrosis, and inflammation. Conclusion: The results indicate that platelet-rich plasma gel surpasses hyaluronic acid in abdominal adhesion prevention.

Enrichment of bread with beta-glucans or resistant starch induces similar glucose, insulin and appetite hormone responses in healthy adults.

PURPOSE: ß-Glucans (ßG) and resistant starch (RS) are known for their effects on the improvement of glucose tolerance and enhancement of insulin sensitivity. Enrichment of bread with ßG or RS was performed to examine potential postprandial benefits regarding gastrointestinal hormone responses. METHODS: Ten healthy normoglycaemic adults participated in the study and were provided with either a glucose solution (reference food, GS) or bread enriched with ß-glucans (ßGB) (3.6 g/30 g available CHO) or bread enriched with resistant starch (RSB) (15% of total starch), with 1-week intervals in amounts that yielded 50 g of available carbohydrates. Venous blood samples were collected before consumption and at 15, 30, 45, 60, 90, 120 and 180 min postprandially. Glucose, insulin, ghrelin, glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) responses as well as glycaemic index (GI) and subjective appetite ratings were evaluated. RESULTS: Ingestion of ßGB and RSB elicited lower incremental area under the curve (iAUC) for glycaemic response compared to GS (P < 0.05). Both breads demonstrated a low GI (ßGB: 48, RSB: 40). There were no significant differences in insulin response, ghrelin, GLP-1 or PYY between the two breads. A significantly lower desire to eat and higher fullness were detected 15 min after ßGB and RSB consumption and until 180 min (P < 0.05 compared to GS). CONCLUSION: Enrichment of bread with either ßG or RS produced a low GI product but the two breads were not significantly different in relation to insulin, ghrelin, GLP-1 and PYY responses. The development of bread products which cause improved metabolic effects is of great importance for the promotion of public health.

gamma-H2AX: A potential biomarker in breast cancer.

Histone H2AX undergoes phosphorylation as an answer to DNA double-strand breaks, which in turn are part of the oncogenic procedure. The detection of gamma-H2AX can potentially serve as a biomarker for transformation of normal tissue to premalignant and consequently to malignant tissues. The aim of this study was to evaluate the clinical significance of gamma-H2AX expression in breast cancer. Gamma-H2AX expression in tissues from 110 breast cancer patients was analyzed by immunohistochemistry and correlated with clinicopathological variables. Greater tumor size, higher grade, and the number of affected lymph nodes are significantly associated with greater values of gamma-H2AX. In addition, gamma-H2AX differs significantly among patients' International Federation of Gynecology and Obstetrics stage. Higher values of estrogen receptor and progesterone receptor are significantly associated with lower gamma-H2AX values. In conclusion, a positive association between gamma-H2AX expression and infaust histopathological parameters was observed.

Healing after Resection of Colonic Endometriosis and Growth Factor-enriched Agents: An Experimental Rat Model.

STUDY OBJECTIVE: To examine the potential beneficial effect of platelet-rich plasma (PRP) and fibrin sealant (TISSEEL; Baxter Healthcare Corporation, Deerfield, IL) on bowel wound healing after shaving of an experimentally induced endometriotic lesion. DESIGN: A single-blind, randomized study (Canadian Task Force classification I). SETTING: A certified animal research facility. ANIMALS: Thirty female Sprague-Dawley rats. INTERVENTIONS: Experimental colonic endometriosis was induced by transplanting endometrial tissue to all animals (first surgery). Thirty rats were then randomized to 1 of 3 groups according to treatment; PRP (group 1, n = 10), fibrin sealant (group 2, n = 10), or no agent (group 3, n = 10) was applied after shaving of the endometriotic nodule (second surgery). MEASUREMENTS AND MAIN RESULTS: Colonic endometriosis was successfully induced in all subjects. Four days after the second surgery, the animals were euthanized, and microscopic evaluation was performed. The pathologist was blinded to the treatment method. Histopathologic analysis revealed that compared with the control group, collagen disposition was found in a significantly higher expression in both the PRP and fibrin sealant groups (p = .011 and p = .011, respectively). Distortion of the integrity of the colon layers was statistically more pronounced in the control group compared with the fibrin sealant group (p = .033), whereas greater new blood vessel formation was observed in the fibrin sealant group compared with the control (p = .023). No histologic evidence of residual or recurrent disease was detected. CONCLUSION: Both PRP and fibrin sealant appear to be safe and associated with improved tissue healing during shaving for the excision of colonic endometriosis, attributed to the enhanced collagen disposition, neovascularization, and protection of the integrity of colon layers. Clinical trials are warranted to confirm the feasibility of PRP and fibrin sealant in the clinical setting.

Canagliflozin attenuates the progression of atherosclerosis and inflammation process in APOE knockout mice.

BACKGROUND: Sodium glucose co-transporter2 inhibitors reduce the incidence of cardiovascular events in patients with type 2 diabetes mellitus based on the results of recent cardiovascular outcome studies. Herein, we investigated the effects of long-term treatment with canagliflozin on biochemical and immunohistochemical markers related to atherosclerosis and atherosclerosis development in the aorta of apolipoprotein E knockout (Apo-E(-/-)) mice. METHODS: At the age of 5 weeks, mice were switched from normal to a high-fat diet. After 5 weeks, Apo-E(-/-) mice were divided into control-group (6 mice) treated with 0.5% hydroxypropyl methylcellulose and Cana-group (7 mice) treated with canagliflozin (10 mg/kg per day) per os. After 5 weeks of intervention, animals were sacrificed, and heart and aorta were removed. Sections stained with hematoxylin-eosin (H&E) were used for histomorphometry whereas Masson's stained tissues were used to quantify the collagen content. Immunohistochemistry to assess MCP-1, CD68, a-smooth muscle actin, MMP-2, MMP-9, TIMP-1 and TIMP-2 expression was carried out and q-PCR experiments were performed to quantify mRNA expression. RESULTS: Canagliflozin-group mice had lower total-cholesterol, triglycerides and glucose levels (P < 0.01), while heart rate was significantly lower (P < 0.05). Histomorphometry revealed that one in seven Cana-group mice versus four in six control mice developed atheromatosis, while aortic root plaque was significantly less, and collagen was 1.6 times more intense in canagliflozin-group suggesting increased plaque stability. Immunohistochemistry revealed that MCP-1 was significantly less expressed (P < 0.05) in the aortic root of canagliflozin-group while reduced expression of a-actin and CD68 was not reaching significance (P = 0.15). VCAM-1 and MCP-1 mRNA levels were lower (P = 0.02 and P = 0.07, respectively), while TIMP-1/MMP-2 ratio expression was higher in canagliflozin-group approaching statistical significance (P = 0.07). CONCLUSIONS: Canagliflozin attenuates the progression of atherosclerosis, reducing (1) hyperlipidemia and hyperglycemia, and (2) inflammatory process, by lowering the expression of inflammatory molecules such as MCP-1 and VCAM-1. Moreover, canagliflozin was found to increase the atherosclerotic plaque stability via increasing TIMP-1/MMP-2 ratio expression.

Controlling type-2 diabetes by inclusion of Cr-enriched yeast bread in the daily dietary pattern: a randomized clinical trial.

PURPOSE: Chromium (Cr)-enriched yeast supplementation to whole wheat bread (WWCrB) has been shown to ameliorate postprandial glycemic response in healthy subjects. The present study investigates the long-term benefit of WWCrB consumption for patients with type-2 diabetes mellitus (T2DM). METHODS: Thirty patients with T2DM were randomly assigned to a group receiving WWCrB or the plain whole wheat bread (WWB) group. Plasma glucose, insulin, glycosylated hemoglobin (HbA1c) and insulin resistance were determined, and oral glucose tolerance test (OGTT) was performed at the beginning and the end of the dietary intervention, which lasted for 12 weeks. Biochemical parameters related to the disease, markers of inflammation as well as body weight and energy balance were examined. RESULTS: At the end of the study, subjects of WWCrB group exerted lower levels of glucose, insulin and HbA1c and improved insulin resistance (P < 0.05 against before treatment). Area under the glucose curve attained during OGTT decreased after the intervention (28,117.5 ± 1266.4 vs. 31,588.5 ± 1187.5 mg min/dL before treatment, P < 0.05) with significantly lower values of glucose concentration at 0 and 60 min. A significant reduction in body weight and systolic blood pressure (SBP) was observed (P < 0.05 against before treatment). Markers of inflammation and lipid profiles were not affected by WWCrB consumption. CONCLUSIONS: Inclusion of WWCrB in the daily dietary pattern of diabetic patients resulted in improvement of glucose tolerance and insulin resistance, significant reduction in HbA1c, weight loss and lower SBP. Patients with inadequate glycemic control may benefit from the consumption of WWCrB.

Comparison of health-related quality of Life (HRQOL) among patients with pre-diabetes, diabetes and normal glucose tolerance, using the 15D-HRQOL questionnaire in Greece: the DEPLAN study.

BACKGROUND: Diabetes mellitus is usually preceded by a pre-diabetic stage before the clinical presentation of the disease, the influence of which on persons' quality of life is not adequately elucidated. The purpose of this study was to compare the Health-Related Quality of Life (HRQOL) of persons with pre-diabetes with that of diabetes or normal glucose tolerance (NGT), using the validated HRQOL-15D questionnaire. METHODS: The HRQOL-15D scores of 172 people with pre-diabetes (108 with Impaired Fasting Glucose [IFG], 64 with Impaired Glucose Tolerance [IGT], aged 58.3 ± 10.3 years) and 198 with NGT (aged 54.4 ± 10.1 years) from the Greek part of the DEPLAN study (Diabetes in Europe - Prevention using Lifestyle, Physical Activity and Nutritional Intervention), were compared to 100 diabetes patients' scores (aged 60.9 ± 12.5 years, diabetes duration 17.0 ± 10.0 years, HbA1c 7.2 ± 1.2%), derived from the outpatient Diabetes Clinic of a University Hospital. RESULTS: The diabetes patients' HRQOL-15D score (0.8605) was significantly lower than the pre-diabetes' (0.9008) and the controls' (0.9092) (p < 0.001). There were no differences in the total score between the controls and the group with pre-diabetes. However, examination of individual parameters of the score showed that people with IGT had lower scores compared to the control group, as related to the parameters of "mobility" and "psychological distress". No differences were found in any component of the HRQOL-15D score between the control group and the IFG group, nor between the two groups with pre-diabetes (IFG vs. IGT). CONCLUSIONS: Persons with pre-diabetes had a similar HRQOL score with healthy individuals, and a higher score than persons with diabetes. Specific components of the score, however, were lower in the IGT group compared to the controls. These findings help clarify the issue of HRQOL of persons with pre-diabetes and its possible impact on prevention.

gamma-H2AX: Can it be established as a classical cancer prognostic factor?

Double-strand breaks are among the first procedures taking place in cancer formation and progression as a result of endogenic and exogenic factors. The histone variant H2AX undergoes phosphorylation at serine 139 due to double-strand breaks, and the gamma-H2AX is formatted as a result of genomic instability. The detection of gamma-H2AX can potentially serve as a biomarker for transformation of normal tissue to premalignant and consequently to malignant tissues. gamma-H2AX has already been investigated in a variety of cancer types, including breast, lung, colon, cervix, and ovary cancers. The prognostic value of gamma-H2AX is indicated in certain cancer types, such as breast or endometrial cancer, but further investigation is needed to establish gamma-H2AX as a prognostic marker. This review outlines the role of gamma-H2AX in cell cycle, and its formation as a result of DNA damage. We investigate the role of gamma-H2AX formation in several cancer types and its correlation with other prognostic factors, and we try to find out whether it fulfills the requirements for its establishment as a classical cancer prognostic factor.

Cr-enriched yeast: beyond fibers for the management of postprandial glycemic response to bread.

PURPOSE: Efforts regarding the amelioration of postprandial glycemic response to bread are mainly focused in the addition of soluble dietary fibers. The current study presents another approach which is based on the supplementation of flour with Cr-enriched yeast. Cr is known for its beneficial effects on improvement of glucose tolerance and enhancement of insulin sensitivity. METHODS: Twelve normoglycemic subjects were provided with white bread (WB, reference food) or whole wheat bread with Cr-enriched yeast (WWCrB, rich in insoluble fibers) or white wheat bread with Cr-enriched yeast (WCrB, poor in fibers) or whole wheat-rye-barley bread enriched with oat beta glucans (BGB, rich in soluble fibers) with 1-week intervals in amounts that yielded 50 g of available carbohydrates. Postprandial glucose, insulin and ghrelin responses as well as glycemic index (GI) were evaluated. RESULTS: Ingestion of WWCrB, WCrB and BGB elicited lower incremental area under the curve (iAUC) for 120-min glycemic response compared to WB (1033.02 ± 282.32, 701.69 ± 330.86 and 748.95 ± 185.42 vs 2070.87 ± 518.44 mg/dL min, respectively, P < 0.05 for WCrB and BGB). The GI was calculated as 62.35 ± 11.78 for WWCrB, 34.22 ± 11.93 for WCrB and 37.90 ± 5.00 for BGB (P < 0.05 vs WB, GI = 100). iAUC for 120-min insulin response to BGB was significantly lower than WB (2780.04 ± 303.26 vs 3915.53 ± 490.57 µU/mL min, P < 0.05), while ghrelin remained suppressed for almost 120 min after the consumption of WWCrB and BGB. CONCLUSIONS: Supplementation of flour with Cr-enriched yeast induces milder postprandial glycemic response to bread without the necessity of high fiber amounts, providing with another strategy for the management of glycemic control.

Levosimendan Improves Neurological Outcome in a Swine Model of Asphyxial Cardiac Arrest.

BACKGROUND: In asphyxial cardiac arrest, the severe hypoxic stress complicates the resuscitation efforts and results in poor neurological outcomes. Our aim was to assess the effects of levosimendan on a swine model of asphyxial cardiac arrest. METHODS: Asphyxial cardiac arrest was induced in 20 Landrace/Large White piglets, which were subsequently left untreated for four minutes. The animals were randomised to receive adrenaline alone (n=10, Group A) and adrenaline plus levosimendan (n=10, Group B). All animals were resuscitated according to the 2010 European Resuscitation Council guidelines. Haemodynamic variables were measured before arrest, during arrest and resuscitation, and during the first 30 minutes after return of spontaneous circulation (ROSC), while survival and neurologic alertness score were measured 24 hours later. RESULTS: Return of spontaneous circulation was achieved in six animals (60%) from Group A and nine animals (90%) from Group B (p=0.303). During the first minute of cardiopulmonary resuscitation, coronary perfusion pressure was significantly higher in Group B (p=0.046), but there was no significant difference at subsequent time points until ROSC. Although six animals (60%) from each group survived after 24 hours (p=1.000), neurologic examination was significantly better in the animals of Group B (p<0.01). CONCLUSIONS: The addition of levosimendan to adrenaline improved coronary perfusion pressure immediately after the onset of cardiopulmonary resuscitation and resulted in better 24-hour neurological outcome.

Autologous transplantation of adipose-derived stem cells enhances skin graft survival and wound healing in diabetic rats.

BACKGROUND: Diabetes can lead to impaired wound healing and skin grafts used surgically for diabetic wounds are often complicated with necrosis, although different therapies have been proposed. Adipose-derived stem cells (ASCs) participate in tissue repair processes and may have a role during impaired wound healing. In this study, autologous transplantation of ASCs was used to determine if it increases angiogenesis and skin graft survival and enhances wound healing in diabetic rats. METHODS: Adipose-derived stem cells were successfully isolated and cultured. A full-thickness skin graft model was used to determine the effects of locally administered ASCs in 10 rats rendered diabetic (group 1), whereas 10 others served as controls (group 2). Histological examination of skin grafts followed after 1 week. Additionally, immunohistochemical staining intensity of vascular endothelial growth factor (VEGF) and transforming growth factor ß3 (TGF-ß3) was assessed in all grafts. RESULTS: The gross and histological results showed significantly increased survival, angiogenesis, and epithelialization. Mean area of graft necrosis was significantly less in group 1 than in group 2 (7.49% vs 39.67%, P < 0.001). Statistically significant increase of capillary density, collagen intensity, VEGF, and TGF-ß3 expression was noted in group 1 compared with group 2. CONCLUSIONS: These findings suggest that autologous ASC transplantation can enhance skin graft survival in diabetic rats through differentiation, vasculogenesis, and secretion of growth factors such as VEGF and TGF-ß3. This might represent a novel therapeutic approach in skin graft surgery for diabetic wounds.

Effects of Incretin Pathway Elements on Bone Properties.

Introduction The effects of incretin-based drugs, such as receptor agonists of glucagon-like peptide-1 and inhibitors of dipeptidyl peptidase-4, on bone metabolism are not completely clear yet. The aim of this study is to compare the effects of glucagon-like peptide-1 and inhibitors of dipeptidyl peptidase-4 on the bone to see how different elements of the incretin pathway affect bone quality in terms of biomechanical properties, bone turnover, and mineral properties. Materials and methods Forty 10-week-old Wistar rats were divided into four groups: a control group, a control diabetic group, a diabetic group treated with sitagliptin, and a diabetic group treated with exenatide. Type 2 diabetes was simulated by dietary manipulation in addition to low-dose streptozotocin, and then two different incretin-based drugs were administered. The rats were sacrificed after five weeks of therapeutic treatment. Their serum was analyzed with the enzyme-linked immunosorbent assay (ELISA) method for basic bone turnover markers, and their right femur was subjected to a three-point bending test. Finally, Hematoxylin & Eosin staining, in addition to Raman spectroscopy, were employed to access the collagen and mineral properties of the bone. Results Both incretin-based drugs reduced osteoclast function; however, they were not able to restore osteoblastic function to normal. The net effect on bone strength was surprising: bone elasticity was restored by the antidiabetic treatment, but bone strength deteriorated. Exenatide had a slightly more pronounced effect, which, although not significant, points to the direction that dipeptidyl peptidase-4 (DPP4) may be a linking factor between reduced osteoclastic function and reduced bone formation, as suggested by the literature. Conclusion DPP4 receptors seem to be one of the links between reduced osteoclast function and reduced bone remodeling, so DPP4 inhibition can be more detrimental to the bone than glucagon-like peptide-1 (GLP-1) receptor agonists.

The Role of MicroRNA-126 in Atherosclerotic Cardiovascular Diseases.

Atherosclerotic cardiovascular diseases remain the leading cause of morbidity and mortality worldwide despite all efforts made towards their management. Other than targeting the traditional risk factors for their development, scientific interest has been shifted towards epigenetic regulation, with microRNAs (miRs) being at the forefront. MiR-126, in particular, has been extensively studied in the context of cardiovascular diseases. Downregulated expression of this miR has been associated with highly prevalent cardiovascular risk factors such as arterial hypertension and diabetes mellitus. At the same time, its diagnostic and prognostic capability concerning coronary artery disease is still under investigation, with up-to-date data pointing towards a dysregulated expression in a stable disease state and acute myocardial infarction. Moreover, a lower expression of miR-126 may indicate a higher disease complexity, as well as an increased risk for future major adverse cardiac and cerebrovascular events. Ultimately, overexpression of miR-126 may emerge as a novel therapeutic target in atherosclerotic cardiovascular diseases due to its potential in promoting therapeutic angiogenesis and anti-inflammatory effects. However, the existing challenges in miR therapeutics need to be resolved before translation to clinical practice.

Long-Term Effect of Diet Consistency on Mandibular Growth within Three Generations: A Longitudinal Cephalometric Study in Rats.

BACKGROUND: This study investigated the effect of diet consistency on mandibular growth of Wistar rats through three generations. METHODS: A total breeding sample of 60 female and 8 male Wistar rats were used in this study. Measurements took place only on female animals. Twenty female Wistar rats at 30 days old and four male rats at 30 days old comprised the primary breeding sample of the first generation, and from these animals two different generations were reproduced. Lateral cephalometric X-rays were taken from all female rats at the age of 100 days. A total of 7 craniofacial landmarks were selected for the linear measurements, and 12 curves and 90 landmarks were selected for geometric morphometric analysis of the lateral X-rays. Bonferroni test and a permutation test were performed for the statistical analysis. RESULTS: Means of measurements of all soft diet groups compared to hard diet groups were significantly smaller. According to linear measurements, there was a significant difference only between the first-generation soft diet with the third-generation soft diet group. According to geometric morphometric analysis, the statistical differences appeared on the condylar process and the angle of the mandible. CONCLUSIONS: The soft diet could be responsible for less mandibular growth, and this information might be passing through generations.

Cardiotrophin-1 in Asymptomatic Hypertensive Patients With Mild Diastolic Dysfunction: Potential Prognostic Value in Early Stages of Hypertensive Heart Disease.

BACKGROUND: Regardless of the advancements in modern technology and treatment options, heart failure (HF) exhibits impervious mortality and morbidity rates. Arterial hypertension poses one of the greatest risks for developing HF, yet the exact pathophysiological path and changes that lead from isolated hypertension to HF are still unclear. Cardiotrophin-1 (CT-1) serves as a promising prognostic biomarker for the onset of HF in hypertensive patients. The aim of this study was to investigate whether CT-1 levels are elevated in a selected group of asymptomatic hypertensive patients. METHODS: In a selected cohort of 40 asymptomatic patients with early diastolic dysfunction (grade I), without any signs of increased filling pressures in the left ventricle, as well as 20 healthy individuals, the levels of CT-1 brain natriuretic peptide (BNP) along with various echocardiographic parameters were evaluated. RESULTS: The mean age of the hypertensive patients was 56 ± 5 years and 52± 3.5 years for the normotensive controls. The hypertensive group exhibited higher levels of CT-1, which was not affected by left ventricular hypertrophy. Notably, in patients with normal E/E' < 8 (n = 30), CT-1 levels were 1165 ± 471 pg/ml compared to 2069 ± 576 pg/ml in patients with marginal E/E' > 8 and <14 (n = 10), p = 0.001. CONCLUSIONS: Our study demonstrated elevated CT-1 levels in a cohort of asymptomatic hypertensive patients, exhibiting mild diastolic dysfunction. These findings are suggestive of the potentially prognostic value of this particular biomarker in the early stages of hypertensive heart disease.

Effects of Diet Consistency on Rat Maxillary and Mandibular Growth within Three Generations-A Longitudinal CBCT Study.

BACKGROUND: In this study, wistar rats were used to examine the impact of diet consistency on maxillary and mandibular growth over three generations. METHODS: In this investigation, a breeding sample of 60 female and 8 male wistar rats was used. Measuring was only performed on female animals. The first generation's primary breeding sample consisted of 20 female wistar rats that were 30 days old and 4 male rats that were also 30 days old; two subsequent generations were created from these animals. At the age of 100 days, CBCTs were collected of all male rats. Twenty-eight craniofacial landmarks were selected for the linear measurements on stl format extracted from the DICOM files. A Bonferroni test was performed for the statistical analysis. RESULTS: Means of measurements of all soft diet groups compared to corresponding measurements of the hard diet groups were significantly different. According to linear measurements, there was statistical difference on the maxillary measurements between the soft diet groups of the first and third generation, while the rest did not appear to have any statistical difference. There was significant difference for the mandibular dimensions only when the first generation soft diet group was compared with the third generation soft diet group. CONCLUSIONS: Food consistency has a significant impact on the growth and development of the maxilla and mandible. Soft diet habits may result in retrognathic mandible, and narrower maxilla.

Propofol prevents lung injury following intestinal ischemia-reperfusion.

BACKGROUND: The antioxidant properties of propofol have been shown to improve ischemia/reperfusion injury. We investigated whether anesthesia with propofol can ameliorate remote lung injury induced by intestinal ischemia-reperfusion (IIR). MATERIALS AND METHODS: Thirty male Wistar rats were randomly allocated in three groups (n = 10 each): animals in group Sham were anesthetized with ketamine and xylazine and then laparotomy and sham IIR followed. Animals in group IIR received ketamine and xylazine and were then subjected to clamping of the superior mesenteric artery for 45 min and reperfusion for 4 h. Group IIR+P received anesthesia with propofol and then IIR was induced, as in group IIR. Blood samples for blood gases and malondialdehyde measurements were drawn at the end of reperfusion. Bronchoalveolar lavage fluid (BALF) was obtained to measure cell counts, total protein, and phospholipids levels. RESULTS: Induction of IIR resulted in deteriorated oxygenation, acidemia, and inflammatory cells sequestration, along with increased BALF protein content and increased proportions of small surfactant aggregates. Anesthesia with propofol alleviated intestinal injury and efficiently prevented lipid oxidation. In group IIR+P inflammatory cell infiltration and pulmonary histologic changes were significantly limited. The increase in BALF total protein and the changes in surfactant aggregates were prevented, leading to normal systemic oxygenation. CONCLUSION: Using propofol to induce and maintain anesthesia efficiently prevented IIR-induced lung injury. Systemic antioxidant protection, improvement of intestinal injury, inhibition of the inflammatory response, and preservation of the alveolar-capillary permeability seem to be crucial mediating mechanisms for this simple and clinically relevant intervention.