Effects of Aloe Vera on healing of colonic anastomoses: experimental rat study / Efeitos da Aloe Vera na cicatrização de anastomoses colônicas: estudo experimental em ratos

ABSTRACT Background: Although herbal medicinal products are being used widely throughout the World, beneficial and harmful effects have not been well documented. Our aim was to evaluate the effects of Aloe Vera (AV) on colonic anastomosis healing. Material and methods: 112 albino Wistar rats were randomly assigned into five main groups: preoperative Aloe Vera Group (P), pre- and postoperative Aloe Vera Group (PP), Control Group (C), sham Aloe Vera Group (SA) and Sham Control Group (SC). Groups P, PP, and SA received 1.6 mL/kg per day Aloe Vera by orogastric feeding catheter for 1 month prior to the experiment. Groups P, PP, and C underwent anastomosis of the distal colon, and subgroups (n = 4) of each were sacrificed on postoperative day 3, 7, 14 and 21. Anastomotic bursting pressure, perianastomotic collagen content and histopathological changes were studied. Results: The SC Group had significantly higher ABP when compared with the SA Group (p = 0.0002), although hydroxyproline content showed no difference. When ABP was compared between anastomosis groups, it was found significantly lower in Aloe Vera groups on Day 3 (P3 vs. C3, p = 0.003 and PP3 vs. C3, p = 0.007). Hydroxyproline content was significantly lower in Group PP than Group C, also on Day 3 (p = 0.05). Significant difference was not detected after Day 3 in any of the study parameters. Conclusion: Aloe Vera decreased tissue collagen content in the early postoperative period. It is advisable to call into question the concomitant usage of conventional medicine and the herbal supplements for the surgeons in their clinical practice.

RESUMO Fundamentação: Embora os medicamentos à base de plantas sejam amplamente utilizados no mundo inteiro, seus efeitos (benéficos e prejudiciais) não estão bem documentados. Este estudo teve como objetivo avaliar os efeitos da Aloe vera (AV) na cicatrização de anastomoses colônicas. Material e métodos: 112 ratos Wistar albinos foram distribuídos aleatoriamente em cinco grupos principais: AV pré-operatório (P), AV pré e pós-operatório (PP), controle (C), sham AV (SA) e sham controle (SC). Os grupos P, PP e SA receberam AV em uma dose de 1,6 mL/kg por dia por sonda de alimentação orogástrica por 1 mês antes do experimento. Os grupos P, PP e C foram submetidos a anastomose do cólon distal. Subgrupos (n = 4) de cada grupo foram sacrificados no terceiro, sétimo, 14° e 21° dias pós-operatórios. Os seguintes parâmetros foram avaliados: pressão de ruptura anastomótica (PRA), conteúdo de colágeno perianastomótico e alterações histopatológicas. Resultados: O grupo SC apresentou PRA significativamente maior quando comparado ao grupo SA (p = 0,0002), embora o conteúdo de hidroxiprolina não tenha apresentado diferença. Ao comparar a PRA entre os grupos de anastomose, ela foi significativamente menor no terceiro dia nos grupos que usaram AV (P3 vs. C3, p = 0,003 e PP3 vs. C3, p = 0,007). No terceiro dia, o teor de hidroxiprolina foi significativamente menor no grupo PP do que no grupo C (p = 0,05). Após o terceiro dia, não se observou diferença significativa em nenhum dos parâmetros do estudo. Conclusão: O uso de AV diminuiu o conteúdo de colágeno tecidual no período pós-operatório imediato. É aconselhável questionar o uso concomitante da medicina convencional e suplementos fitoterápicos na prática clínica.

Role of new biomarkers for predicting renal scarring in vesicoureteral reflux: NGAL, KIM-1, and L-FABP.

BACKGROUND: Reflux nephropathy is the most serious complication of vesicoureteral reflux (VUR). The aim of this study was to assess the role of urinary levels of neutrophil-gelatinase-associated lipocalin (NGAL),kidney injury molecule-1 (KIM-1), and liver-type fatty-acid-binding protein (L-FABP) in the early diagnosis of reflux nephropathy in patients with VUR. METHODS: This study assessed 123 patients with primary VUR and 30 healthy children as a control group. The children were divided into five groups: Group A, patients with VUR and renal parenchymal scarring (RPS); Group B, patients with VUR and without RPS; Group C, patients with RPS and resolved VUR; Group D, patients with resolved VUR and without RPS; Group E, healthy reference group. RESULTS: Median urinary NGAL (uNGAL)/Creatinine (Cr) was significantly higher in patients with than those without RPS and the control group (p = 0.0001). Median uKIM-1/Cr was similar in all groups (p = 0.417). Median uL-FABP/Cr was significantly higher in patients with RPS than in the reference group (p < 0.05). CONCLUSIONS: Urinary NGAL levels may be used as a noninvasive diagnostic marker for predicting renal scarring in reflux nephropathy.

Urinary NGAL, KIM-1 and L-FABP concentrations in antenatal hydronephrosis.

INTRODUCTION: The clinical tests currently in use for obstructive nephropathy (such as renal ultrasonography, differential radionuclide renal scans and urinary creatinine concentration data) are not efficient predictors of the subsequent clinical course. Novel and simple biomarkers are required which, if proven, could be clinically beneficial in determining if a patient is eligible for surgery or reno-protective therapy. More recently, the interest of clinicians has focused on the potential of urinary neutrophil gelatinase-associated lipocalin (uNGAL), urinary kidney injury molecule-1 (uKIM-1) and urinary liver-type fatty acid-binding proteins (uL-FABP) as biomarkers for renal function in children with hydronephrosis (HN). OBJECTIVE: The purpose of this study was to investigate possible clinical applications of uNGAL, uKIM-1 and uL-FABP as beneficial non-invasive biomarkers to determine whether or not surgical intervention is required in children with HN. STUDY DESIGN: Renal ultrasonography and radionuclide renal scans were used as diagnostic tools to detect HN. Patients were divided into two groups based on the antero-posterior diameter of their renal pelvis and the presence of dysfunction. Group 1 included 26 children with severe HN (with dysfunction), and group 2 consisted of 36 children with mild HN (without dysfunction). Urine samples were collected from 62 children with HN and 20 healthy children. RESULTS: Hydronephrosis was more common in males than in females, with a male to female ratio of 9:1 in the study sample. The incidence of left kidney involvement (32 patients) was slightly higher than right kidney involvement (28 patients). Compared with controls and group 2, the ratio of uNGAL to creatinine was significantly higher in group 1 (p < 0.05). The biomarker uNGAL/Cr exhibited fairly good diagnostic accuracy, with an area under the curve of 0.68 [95% confidence interval 0.6-0.7] and an optimal cut-off value of 0.16 ng/mg Cr (sensitivity 58%, specificity 75%) (p < 0.05). There was a positive correlation between the uNGAL/Cr ratio and the uKIM-1/Cr ratio (r = 0.582, p < 0.05) and uL-FABP/Cr ratio (r = 0675, p < 0.05) in group 1. DISCUSSION: The results clearly demonstrated that children with hydronephrosis and dysfunction had significantly increased uNGAL, and uNGAL/Cr concentrations. However, uKIM-1, uKIM-1/Cr, uL-FABP and uL-FABP/Cr concentrations were not significantly different when compared with controls. These results support the use of uNGAL concentrations as an early marker for renal dysfunction in HN. CONCLUSIONS: The study clearly demonstrated that pediatric patients with hydronephrosis and dysfunction had significantly higher uNGAL to creatinine concentrations as compared with controls.

Investigation of the Plasma Nitrite Levels and Oxidant-Antioxidant Status in Obstructive Sleep Apnea Syndrome.

INTRODUCTION: Obstructive sleep apnea (OSA) is one of the most prevalent sleep disorders. In the present study, we assessed the nitrite level, which is an indirect indicator of nitric oxide (NO), total oxidant status (TOS), total antioxidant status (TAS) and oxidative stress index (OSI), which may be associated with endotel dysfunction. We investigated the difference between the groups and the relationship among the severity of comorbid conditions. METHODS: This study was conducted in 39 OSA patients confirmed by polysomnography and 40 healthy subjects (controls). The OSA group consisted of 10 women and 29 men and the control group consisted of 20 women and 20 men. Polysomnographic revealed mild OSA in two, moderate in 7 and severe in 30 cases. We measured plasma TAS, TOS and nitrite levels from venous blood. The OSI value was obtained by dividing the TOS and TAS values. Values were compared with the control group and between patient groups. RESULTS: A high body mass index (BMI), cardiovasculer diseases (CVD) and the use of medication for co-morbid diseases were more prevalent in the OSA group (p=.001, p=.029 and p=.006, respectively). The median plasma TOS level and OSI in the obstructive sleep apnea syndrome (OUA) group were significantly higher than those in the control group (p=.001 and p=.001, respectively). The plasma median nitrite level and TAS did not show any significant difference between the OSA and the control groups. None of the parameters revealed a significant difference between severe and moderate OSA cases. CONCLUSION: Our findings in the present study revealed that the oxidant-antioxidant balance shifted toward the oxidant side in OSA cases; however, the NO level did not change. These findings together may point out that some molecules other than NO may have a role in the pathophysiology of endothelial dysfunction and also in the disturbed oxidant-antioxidant balance in OSA.

Nitric oxide in gingival crevicular fluid and nitric oxide synthase expression in the gingiva of patients with sickle cell disease.

OBJECTIVE: This study aimed to biochemically measure the production of nitric oxide in gingival crevicular fluid and immunohistochemically measure the expression of inducible nitric oxide synthase in the gingiva of patients with sickle cell disease. Additionally, we aimed to obtain insight into the immunopathology of sickle cell disease by comparing inducible nitric oxide synthase levels in patients with sickle cell disease and controls using gingiva and gingival crevicular fluid. METHODS: The study included 20 sickle cell disease patients and 20 healthy controls. Immunohistochemical analysis was used to measure inducible nitric oxide synthase expression in gingiva and nitric oxide levels in gingival crevicular fluid were spectrophotometrically measured. RESULTS: Nitric oxide levels in the patients and controls did not differ significantly (21.2±4.5 and 23.1±2.3 µM L-1, respectively, p>0.05). There weren't any statistically significant differences in infiltrated inflammatory cells, density of inflammatory cells that stained with inducible nitric oxide synthase, or nitric oxide expression in gingiva between the patient and control groups (p>0.05). CONCLUSION: To the best of our knowledge this is the first study to examine the expression of inducible nitric oxide synthase in the gingiva and gingival crevicular fluid in patients with sickle cell disease. Using the gingiva and gingival crevicular fluid we were unable to observe sickle cell disease-associated inducible nitric oxide synthase expression and a difference in nitric oxide levels.

Carotid artery thickness in children and young adults with end stage renal disease.

Atherosclerosis is a major cause of morbidity and mortality for ESRD patients and we have little knowledge about the presence and risk factors of atherosclerosis in children with CRF. The measurement of carotid artery intima-media thickness (cIMT) using high-resolution ultrasonography is suggested as an excellent marker of subclinical atherosclerosis. In this study, we aimed to investigate the presence of atherosclerosis and to determine the relationship between atherosclerosis and some risk factors in children and young adults with ESRD. Thirty-four patients with ESRD and 20 controls were included in this study. The measurement of cIMT was performed by using a linear B-mode 7.5-MHz ultrasound transducer. We determined anemia, abnormal calcium/phosphate metabolism, hyperhomocysteinemia, hypertriglyceridemia and increased lipoprotein (a) levels in the ESRD group. The cIMT in the ESRD group was higher than in the control group (P<0.05). SBP, DBP, MAP, LVMI and LVH prevalence were statistically higher in the ESRD group (P<0.05). There were significant positive correlations between cIMT and LVMI, MBP, whereas a significant negative correlation was determined between cIMT and PTH in the ESRD group (P<0.05). When a multiple linear regression analysis was performed with cIMT as a dependent variable and LVMI, MBP, PTH, as independent variables, a significant positive correlation was determined between cIMT and LVMI (P<0.05). In conclusion, we think that arteriopathy occurs in children with ESRD. Left ventricular hypertrophy and hypertension may associate with vascular changes in children and young adults with ESRD. Further investigations are necessary to explain association of LVMI index with cIMT.

Peritoneal clearance of biochemical markers of bone turnover in children with end stage renal failure on peritoneal dialysis.

Renal osteodystrophy is one of the important complications in children with end stage renal disease. Non-invasive tools for evaluation of bone metabolism have been proposed in recent years. The aim of this study was to investigate the markers of metabolic bone disease and peritoneal clearance of these markers in children treated with continuous ambulatory peritoneal dialysis (CAPD). In this study, serum osteocalcin (OC) levels were found significantly higher in patients (107.98 +/- 99.99 ng/ml) than in the healthy control group (41.94 +/- 12.94 ng/ml; p<0.05). Mean peritoneal clearance (Clp) of OC was 0.87 +/- 0.91 ml/min. There was no correlation between serum OC and Clp-osteocalcin. There was a positive correlation between serum phosphorus (P) and OC (r=0.394, p=0.031), alkaline phosphatase (ALP) and OC (r=0.520, p=0.003), and parathyroid hormone (PTH) and OC (r=0.441, p=0.017), whereas no correlation was found between OC and calcium (Ca) and OC and magnesium (Mg). There was also a significant correlation between serum ALP and PTH (r=0.714, p=0.0001). A positive correlation was found between serum PTH and Clp of PTH (r=0.471, p=0.009). In conclusion, Clp-osteocalcin is of no interest as a non-invasive marker of metabolic bone disease in children treated with CAPD. But significant correlation between serum OC and PTH, P, and ALP shows that serum OC could be used as a valuable non-invasive biochemical marker of metabolic bone disease.

Effects of a static magnetic field on wound healing: results in experimental rat colon anastomoses.

BACKGROUND: Research has shown that pulsed electromagnetic fields (EMFs) promote wound healing in experimental colonic anastomosis; however, the effects of static EMFs in this setting have not been investigated to date. METHODS: Fifty male Wistar rats were used. Ten served as controls for mechanical strength testing, and the other 40 underwent descending colon resection and anastomosis. Twenty of these 40 animals (M group) had NeFeB magnets placed in contact with the anastomosis site (magnetic field strength at the site 390 to 420 G). The other 20 animals (sham [S] group) had non-magnetized NeFeB bars of the same dimensions and weight implanted. Half of the animals in each group were killed and assessed for healing parameters on postoperative day 3 (M3 and S3 groups) and the other half on postoperative day 7 (M7 and S7 groups). Four types of assessment were done: gross healing, mechanical strength, hydroxyproline deposition, and histopathology. RESULTS: There were no differences between the M and S animals with respect to gross healing parameters. The mechanical strength was also not different between groups (23.8 +/- 12.7 and 24.7 +/- 9.6 mm Hg for M3 and S3, respectively; P = .863 and 91.3 +/- 65.4 and 94.8 +/- 55.9 mm Hg for M7 and S7, respectively; P = .902). Similarly, hydroxyproline deposition was not different between groups on postoperative day 3 or day 7. On postoperative day 3, the M group had significantly higher scores than the S group for fibroblast infiltration (2.4 +/- 0.7 vs 1.4 +/- 0.7, respectively; P = .008) and capillary formation (2.5 +/- 0.7 vs 0.9 +/- 0.4, respectively; P <.001). However, these effects were reversed and did not endure by day 7. CONCLUSIONS: The study results suggest that static EMF has no effect on experimental colonic wound healing in the rat.

Helicobacter pylori eradication lowers serum homocysteine level in patients without gastric atrophy.

AIM: To determine whether Helicobacter pylori (H pylori)infection caused hyperhomocysteinemia by altering serum vitamin B(12), serum folate and erythrocyte folate levels and whether eradication of this organism decreased serum homocysteine level. METHODS: The study involved 73 dyspeptic H pylori-positive patients, none of them had gastric mucosal atrophy based on rapid urease test and histology. Out of 73 patients, 41 (56.2%) showed a successful eradication of H pylori 4 wk after the end of treatment. In these 41 patients, fasting serum vitamin B(12), folate and homocysteine levels, and erythrocyte folate levels before and 4 wk after H pylori eradication therapy were compared. RESULTS: The group with a successful eradication of H pylori had significantly higher serum vitamin B(12) and erythrocyte folate levels in the post-treatment period compared to those in pre-treatment period (210+/-97 pg/mL vs 237+/-94 pg/mL, P<0.001 and 442+/-212 ng/mL vs 539+/-304 ng/mL, P = 0.024, respectively), but showed no significant change in serum folate levels (5.6+/-2.6 ng/mL vs 6.0+/-2.4 ng/mL, P = 0.341). Also, the serum homocysteine levels in this group were significantly lower after therapy (13.1+/-5.2 micromol/L vs 11.9+/-6.2 micromol /L, P = 0.002). Regression analysis showed that serum homocysteine level was positively correlated with age (P = 0.01) and negatively with serum folate level before therapy (P = 0.003). CONCLUSION: Eradication of H pylori decreases serum homocysteine even in patients who do not exhibit gastric mucosal atrophy. It appears that the level of homocysteine in serum is related to a complex interaction among serum vitamin B(12), serum folate and erythrocyte folate levels.

Glycosaminoglycans in childhood urinary tract infections.

It has been suggested that urinary glycosaminoglycans (GAGs) form a natural defense mechanism against urinary tract infections (UTIs). This study investigated whether urinary GAGs play a role in pediatric UTIs, and whether urinary GAG level can be used to differentiate upper UTI from lower UTI. Forty-one children with UTIs (33 girls and eight boys; mean age 5.4+/-3.7 years) and 46 age- and sex-matched healthy children (35 girls and 11 boys; mean age 6.6+/-3.9 years) were included in the study. Urinary GAG levels were measured at the onset of acute infection and after a 10-day course of antibiotic treatment. Group GAG findings were compared, and comparisons were also made with the patients divided according to sex and according to UTI type (upper versus lower). The mean urinary GAG level in the patient group at the onset of acute infection (pretreatment) was significantly higher than the mean level in the control group (132.2+/-104.8 mg/g vs 42.2+/-27.1 mg/g creatinine, respectively; P <0.01). In the patient group, the mean urinary GAG level after antimicrobial therapy was significantly lower than the pretreatment level (75.9+/-52.1 mg/g vs 132.2+/-104.8 mg/g creatinine, respectively; P <0.01). However, the mean post-treatment level was still higher than the mean level in the controls ( P <0.05). There was no significant difference in urinary GAG levels when patients were categorized as upper versus lower UTI ( P >0.05). The study results suggest that GAGs play an important role in the pathogenesis of UTIs in children, and that measurement of urinary GAGs may be a valuable noninvasive method for evaluating UTIs in this patient group. However, this assay cannot be used to differentiate upper UTI from lower UTI in children.

Glycosaminoglycan excretion in children with nephrotic syndrome.

Although most childhood nephrotic syndromes respond to steroid treatment, steroid resistant nephrotic syndrome (SRNS) is also common and is particularly difficult to treat. This study investigated the role of glycosaminoglycans (GAG) in the pathogenesis and clinical course of nephrotic syndrome in children. Thirty-four children (21 males and 13 females, mean age 3.7+/-1.6 years) with steroid-sensitive nephrotic syndrome and 20 children with steroid-resistant nephrotic syndrome (12 males and 8 females, mean age 10.9+/-3.8 years; of the twenty, four had primary SRNS (FSGS) and the others had secondary SRNS) were included the study. Mean urine levels of GAG relative to creatinine (U(GAG)/U(Cr)) in patients with SRNS (n=20, 113.01+/-78.46 mg g(-1) Cr) and in patients experiencing the nephrotic period of steroid-sensitive nephrotic syndrome (n=34, 132.15+/-101.55 mg g(-1) Cr) were both significantly higher than mean U(GAG)/U(Cr) for control subjects (n=30, 51.83+/-47.66 mg g(-1) Cr) (P<0.01 for both). Patients excreted significantly more GAG during the nephrotic period of steroid-sensitive nephrotic syndrome than during remission (132.15+/-101.55 vs 39.11+/-42.73 mg g(-1) Cr, respectively; P<0.01). There was, however, no significant difference between U(GAG)/U(Cr) for patients with steroid-resistant nephrotic syndrome and U(GAG)/U(Cr) in the nephrotic period of steroid-sensitive nephrotic syndrome. Urine GAG excretion correlated significantly with the severity of proteinuria. The results suggest that GAG play a significant role in the pathogenesis of nephrotic syndrome but that GAG excretion is not a marker for response to steroid treatment in pediatric patients with this condition.

The effect of tissue adhesive, octyl-cyanoacrylate, on the healing of experimental high-risk and normal colonic anastomoses.

BACKGROUND: Tissue adhesives may be advantageous over sutures in colonic anastomoses because they do not result in potentially dangerous tight tissue approximation. METHODS: Ninety male Wistar-albino rats were used in the study. Excluding the 10 animals that constituted the control, the rest of the animals were divided in two groups: normal (N) and high-risk (HR). Only resection and anastomosis were done on half of the animals in each group. Octyl-cyanoacrylate was applied on the anastomosis of the other half of the groups. Anastomotic assessment was done at the third and seventh postoperative days. Gross anastomotic healing, mechanical strength, hydroxyproline deposition, and histopathological healing indices were used for the assessment. RESULTS: There was no difference in the third day and the seventh day groups regarding the gross healing parameters and hydroxyproline concentration. Similarly there was no difference between the third day groups in terms of mechanical healing (P = 0.669). However, the mechanical strength of the anastomosis assessed the seventh postoperative day was lower in groups in which octyl-cyanoacrylate was applied (P <0.001). Furthermore, inflammatory reaction, presence of necrosis, peritonitis, and exudate was pronounced in groups in which octyl-cyanoacrylate was applied. CONCLUSIONS: Application of octyl-cyanoacrylate to both normal and high-risk colonic anastomosis does not provide any benefit over conventional suturing at the early phase of the healing. However, octyl-cyanoacrylate seems to be detrimental at the late phase of the healing probably due to the ongoing intense inflammatory reaction.

Association between postprandial hyperinsulinemia and coronary artery disease among non-diabetic women: a case control study.

BACKGROUND: We planned a case-control study to assess the relation of fasting glucose, fasting insulin, postprandial glucose and postprandial insulin levels with coronary artery disease in nondiabetic women. METHODS: Among 968 consecutive nondiabetic women screened, 104 with coronary artery disease (mean age 60, 4+/-9) made up the study cohort (group I). One-hundred and four age-matched, nondiabetic women without coronary artery disease who had a similar lipid and blood pressure profile (group II), and 52 healthy, age-matched women served as controls (group III, real control group). Demographics, waist circumference, lipids, fasting glucose postprandial glucose, fasting and postprandial insulin levels were compared among the groups. A separate subgroup analysis were performed in patients with metabolic syndrome. RESULTS: No differences were identified in terms of prevalences of risk factors between group I and group II. Women with coronary artery disease had higher postprandial insulin level than the women in group II and group III. In reverse stepwise logistic regression analysis postprandial hyperinsulinemia was found to be the single independent determinant for coronary artery disease for the entire study group as well as for women with metabolic syndrome. CONCLUSION: Our data demonstrate that postprandial hyperinsulinemia is independently associated with coronary artery disease, irrespective of fasting glucose, postprandial glucose, and fasting insulin levels in nondiabetic women with clusterings of factors of metabolic syndrome.

The effects of gemfibrozil on hyperlipidemia in children with persistent nephrotic syndrome.

Persistent nephrotic syndrome is frequently accompanied by severe hyperlipidemia, and this may pose a substantial risk for cardiovascular disease. Lipid-lowering drugs are prescribed by many nephrologists for adult patients but rarely for nephrotic children. The present investigation was designed to evaluate the safety and efficacy of gemfibrozil in nephrotic children. Eight girls and four boys aged from 5 to 17 years were enrolled in this study. They were all steroid and immunosuppressive resistant patients with nephrotic range proteinuria. Placebo was administered to five patients and gemfibrozil was administered to seven patients for four months. Blood samples were taken for the determination of cholesterol, triglyceride, low-density lipoprotein (LDL), high-density lipoprotein (HDL), BUN, serum creatinine (Scr), ALT, AST, CPK, apolipoprotein A (apo A), apoliporotein B (apo B), and serum albumin levels during the initial and subsequent examinations. At the end of the fourth month, gemfibrozil reduced total cholesterol by 34%, LDL by 30%, apo B by 21% and triglycerides by 53% (p < 0.05). HDL cholesterol and apo A levels were not significantly altered. Renal function and urine protein excretion were not affected by gemfibrozil. In this study gemfibrozil therapy had no side effects and had favorable effects on the lipoprotein profile of nephrotic patients.