Effects of Kaurenoic Acid and Arginine on Random Skin Flap Oxidative Stress, Inflammation, and Cytokines in Rats.

BACKGROUND: Kaurenoic acid (KA), a diterpene extracted from copaíba oil-resin, is known to have potent antioxidant and anti-inflammatory properties. L-Arginine (LA) is an amino acid and a nitrogenous precursor for the synthesis of nitric oxide (NO). NO paper in wound healing has already been well documented. The aim of this study was to investigate the protective effects of LA and KA against ischemia reperfusion injury in a randomized skin flap model in rats. METHODS: A modified McFarlane flap model measuring 2.5 wide × 8 cm long was established in 36 anesthetized rats and evaluated within 3 groups: group control, group L-arginine, and group kaurenoic acid. Each group was subdivided into two subgroups (T1 and T2, n = 6 each). Samples were collected 24 h (T1)/48 h (T2) postoperatively for oxidative stress (glutathione), as non-protein thiols, malondialdehyde (MDA), NO2, inflammation [myeloperoxidase (MPO)], and cytokines TNF-α and IL-1ß assays. RESULTS: KA promoted a significant decrease of TNF-α and IL-1 expression and MPO activity at T1/T2 time points. NSGH levels increased significantly in KA-treated rats, while MDA levels decreased significantly in the same rats. Arginine promoted a significant decrease in MDA levels at the T1 time point and a significant increase in non-protein thiols concentrations at T1/T2 time points. NO2 concentration also decreased at the T1 time point. CONCLUSIONS: KA may attenuate the oxidative stress and the inflammation, thereby reducing tissue damage induced by ischemia/reperfusion in rats subjected to dorsal skin flaps. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors http://www.springer.com/00266.

Electroacupuncture attenuates oxidative stress in random skin flaps in rats.

BACKGROUND: Skin flaps may be damaged by free radicals produced during blood reflow and oxygen return to ischemic tissues. Considering that published studies have demonstrated the effects of manual acupuncture (MA) and electroacupuncture (EA) in attenuating the oxidative stress in different tissues and organs, this study aimed to investigate the possible protective effects of MA and EA in randomized skin flaps in rats. METHODS: Thirty-two rats were subjected to dorsal skin flap (8 × 2.5 cm) construction and randomly divided into four groups of eight rats each: G1, surgical trauma; G2, MA; G3, EA 3 Hz; and G4, EA 100 Hz. All rats were anesthetized with ketamine (90 mg/kg) + xylazine (10 mg/kg) intraperitoneally on days 1, 3, and 7. MA (G2) and EA (G3/G4) were applied on days 3 and 7 of the experiment. G3 and G4 rats were treated with EA 3 and 100 Hz, respectively. Needles were inserted in GV-14 (Dazhui), GV-2 (Yaoshu), and L-13 (Zhangmen) acupoints and retained for 30 min. Blood and skin samples were collected at the end of the last procedure. The ANOVA/Dunnett test was used for group comparison. Values of p < 0.05 were considered significant. RESULTS: Skin myeloperoxidase (MPO) activity decreased significantly in G2, G3, and G4 rats. Plasma and skin levels of reduced glutathione (GSH) increased significantly in G3 and G4 rats (p < 0.001) compared with G1 control. Malondialdehyde (MDA) plasma and skin levels increased significantly in G4 compared with G1 rats. CONCLUSIONS: MA/EA decreased MPO activity in the graft, consistent with attenuated inflammation, and increased plasma and tissue GSH, indicative of reduced systemic and local oxidative stress. EA at 100 Hz enhances lipid peroxidation in plasma and skin of rats subjected to surgical stress. LEVEL OF EVIDENCE II: This journal requires that authors assign a level of evidence to each article.

Oxidative stress in follicular units during hair transplantation surgery.

BACKGROUND: Hair transplantation surgery currently is a well-established procedure in plastic surgery. It consists of harvesting a strip of scalp from the back of the head, then obtaining grafts called follicular units (FUs) from this strip and implanting them in the bald area. The FUs undergo oxidative stress during cold ischemia and after their implantation. METHODS: Surgery was performed for 18 patients between April and July 2008. Follicular units were preserved in solutions containing different growth-stimulating hormone (GSH) concentrations (5, 10, and 20 mmol). Saline solution was used as a control condition. Spectrophotometry was used to measure the thiobarbituric acid-reactive substance (TBARS) and GSH concentrations before ischemia (control group) in the FUs preserved in the four proposed solutions, then after 30 min of cold ischemia and 30 min after grafting. The data obtained were submitted to analysis of variance, t test, and linear regression analysis. RESULTS: The TBARS (µmol of malondialdehyde [MDA]/g) and GSH (µmol/g) concentrations were not significantly different between the four solutions in either the ischemia or grafting group. The GSH concentration did not differ significantly between the control (59.801 ± 30.639 µmol/g) and ischemia (56.284 ± 28.404 µmol/g) groups. The GSH concentrations were significantly greater (p < 0.05) in the postgrafting group (63.815 ± 28.404 µmol/g) than in the group subjected to ischemia. CONCLUSION: Increasing the GSH concentrations used in FU preservation solutions does not reduce the oxidative effects of cold ischemia and reperfusion injury during hair transplantation surgery.

Use of continuous glucose monitoring system in patients with type 2 mellitus diabetic during hemodialysis treatment.

BACKGROUND: Studies highlight the inaccuracy of glycated hemoglobin (HbA1c) for the assessment of glycemic control in dialysis diabetics and suggest the use of continuous glucose monitoring (CGM) as an alternative. Of the CGMs, FreeStyle Libre® is the most used in worldwide, but there is still no consensus on its use in dialysis. METHOD: A 3-week prospective study was performed with 12 patients comparing capillary and interstitial glucose during dialysis. RESULTS: Comparing capillary and interstitial measurements, similar values were observed in pre-dialysis in the 1st week (184.1 ± 69.5 mg/dl and 173.1 ± 78.9 mg/dl, respectively, p = 0.303), in patients with body mass index less than 24.9 kg/m2 (214.2 ± 72.2 mg/dl and 201.3 ± 77.0 mg/dl respectively, p = 0.466), in those dialysis fluid loss less than 2 l (185.5 ± 82.6 mg/dl and 183.1 ± 94.0 mg/dl respectively and p = 0.805) and in those with hemoglobin greater than 12 g/dl (152.0 ± 35, 5 mg/dl and 129.5 ± 47.4 mg/dl respectively, p = 0.016). In the correlation of the capillary measurement with the interstitial sensor, it was observed that the proportions in the Clarke Error Grid of zone A, zone B, zone C, zone D and zone E were 62.5%, 27.1%, 0.0%, 10.4% and 0.0% respectively and in the Parkes error grid in zone A, zone B, zone C, zone D and zone E were 80.6%, 9.7%, 9.7% 0.0% and 0.0%, respectively. CONCLUSION: The mean absolute relative difference in dialysis patients is higher than the general population without end-stage renal disease. However, clinical decision-making based on the values measured by the system can be made with a good margin based on the correlation between interstitial and capillary measurements.

L-alanyl-glutamine preoperative infusion in patients with critical limb ischemia subjected to distal revascularization reduces tissue damage and protects from oxidative stress.

BACKGROUND: Critical limb ischemia (CLI) is the most severe form of peripheral vascular disease where there is inadequate blood flow to a limb. Our aim was to examine the effects of preoperative infusion of l-alanyl-glutamine (l-Ala-Gln) during the ischemic period and during the first 30 minutes following blood reflow in patients with CLI who are undergoing distal femoral artery bypass surgery. METHODS: Thirty-two patients with CLI were alternately allocated to group 1 (saline) or group 2 (l-Ala-Gln). Saline (1000 mL) or L-Ala-Gln 250 mL plus 750 mL of saline were infused intravenously over a 3-hour period prior to surgery. Samples (muscle and blood) were collected at the beginning of the surgical procedure, at the end of ischemia, and at 15 and 30 minutes after reperfusion. RESULTS: l-Ala-Gln induced elevation in glutathione (GSH) muscle concentrations while promoting reduction in thiobarbituric acid reactive substance concentrations, demonstrating enhancement of antioxidant capacity and protection from lipid peroxidation. Decreases in LDH, lactate, and glucose blood concentrations in l-Ala-Gln-treated patients suggest increased glucose utilization by muscle and peripheral tissues. Reduction in creatine phosphokinase blood concentrations may reflect smaller muscle cell damage in l-Ala-Gln-treated patients. CONCLUSION: l-Ala-Gln pretreatment reduces muscle cell damage and enhances antioxidant capacity in patients with CLI.

Effects of Copaifera langsdorffii Desf. on ischemia-reperfusion of randomized skin flaps in rats.

BACKGROUND: Copaíba oil is an oleoresin obtained from the Copaiffera langsdorffii genus (Leguminoseae). It is widely used in folk medicine as an antiinflammatory, healing, and antiseptic agent. Comparative pharmacologic studies between different species of copaíba oils are scarce. METHODS: The protective effect of Copaiffera langsdorffii was evaluated on an experimental model of random skin flaps on rat dorsums. RESULTS: Seventy-two Wistar rats (average weight = 216.8 g) were divided randomly into four equal groups (saline control, vehicle control, GT200-Test 1, and GT400-Test 2). A caudally based rectangular flap, 2.5-8.0 cm in size, was elevated on the back of the rat using McFarlane's method. The flap was sutured back into its original place. Copaifera and control drugs (saline and Tween 80) were administered by gavage 24, 12, and 2 h prior to the beginning of the experiment followed by daily doses for the next 7 days. To observe the effects of Copaifera, laboratory analyses included plasma and tissue levels of tiobarbituric acid-reactive substances (TBARS) and reduced glutathione (GSH) and tissue levels of myeloperoxidase (MPO). CONCLUSION: The oil-resin of copaíba presents discrete antilipoperoxidation action, intense antioxidant action, and antiinflammatory activity during the ischemia and reperfusion of randomized cutaneous flaps. The effects of ischemia-reperfusion are complex and substances capable of increasing the tolerance of tissue to those effects by reducing the production or neutralizing the action of free radicals are needed.

Protective effect of alpha-lipoic acid in experimental spermatic cord torsion.

OBJECTIVE: We investigated the effect of alpha-lipoic acid (LA) in rats that were subjected to torsion/detorsion of the spermatic cord in a comparative controlled experiment. METHODS: Forty-eight male Wistar rats, randomized in two groups, received intraperitoneal injections of LA (LA group; aqueous solution at 36 mg/kg of body weight per day) or equal volume of saline (control group) 21, 9, and 1 h before torsion of the spermatic cord. Rats in each group were distributed in four subgroups, each comprising six animals. All surgical procedures were performed under inhaled ether anesthesia. Ischemia was induced by 720-degree torsion of the spermatic cord for 3 h. The right testis was assessed through longitudinal scrotal incision. After each surgical procedure, scrotal incisions were closed with 4-0 nylon monofilament. Ipsilateral testes and arterial blood samples were collected at the end of ischemia and 1, 3, and 6 h after detorsion. Thiobarbituric acid-reactive substances and reduced glutathione levels (micromoles per gram of wet tissue) were assayed in testis. Total antioxidant power was measured in blood plasma. RESULTS: LA pretreatment promoted a significant decrease in testicular concentrations of thiobarbituric acid-reactive substances and simultaneously induced an increase in reduced glutathione concentrations at all time points studied. Plasma total antioxidant power levels increased significantly during reperfusion (T-1) in LA-treated rats compared with control rats. CONCLUSION: LA administered before torsion of the spermatic cord showed significant protective effects against ischemia/reperfusion injury by decreasing lipid peroxidation and regulating testicular reduced glutathione and plasma total antioxidant power levels.

Glutamine or whey-protein supplementation on alloxan-induced diabetic rats. Effects on CD4+ and CD8+ lymphocytes.

PURPOSE: To evaluate the effects of glutamine (L-Gln) or whey-protein supplementation on CD4+ and CD8+ lymphocytes in alloxan-induced diabetic rats. METHODS: Thirty-two healthy male Wistar rats were used in the experiment. Eight rats served as baseline controls (G-1). The remaining 24 animals received alloxan 150 mg/Kg intraperitonially dissolved in buffer solution and were equally distributed in 3 subgroups, upon induction of diabetes mellitus, and treated as follows: (G2): saline, 2.0 ml; (G3): glutamine solution (0.7 g/kg), 2.0 ml; and (G4): whey-protein (WPS) solution (0.7 g/kg), 2.0 ml. All solutions were administered by daily 7:00 AM gavages during 30 days. Next, arterial blood samples (3.0 ml) were collected from anesthetized rats for CD4+ and CD8+ lymphocyte count through flow cytometry technology. RESULTS: CD4+ and CD8+ counts decreased significantly in all groups compared with baseline values (G1). G2 rats CD4+/CD8+ ratio decreased significantly compared with G1. CD4+/CD8+ ratio increased significantly (>260%) in L-Gln treated group (G3) compared with saline-treated rats (G2). There were no statistical differences in lymphocyte counts (CD4+ and CD8+) between L-Gln (G3) and saline-treated (G2) groups. There was a significant reduction in CD8+ cell count compared with CD4+ cell count in L-Gln treated rats (G3). CONCLUSION: The offer of L-Gln to experimental diabetic rats enhances the immunologic response to infection.

Oxidative stress induced by torsion of the spermatic cord in young rats.

PURPOSE: To evaluate the effects of the oxidative stress in an experimental model of torsion/detorsion of the spermatic cord and the legitimacy of this model for oxidative stress studies. METHODS: Forty-eight male Wistar rats were randomized in two groups (n=24): G-1 (Sham) and G-2 (Ischemia/Reperfusion). All rats received intraperitoneal saline injections (2.0 ml), at 21, 9, and 1 h before right spermatic cord torsion or first sham operation. Detorsion or second sham operation was carried out 3 h later followed by testis and blood samples collection (T-0). Additional samples were collected at 1-3-6 h time-points for assessment of testis malonaldehyde, glutathione, and plasma total antioxidant power (TAP). RESULTS: Spermatic cord torsion/detorsion induced a significant increase in testicular malonaldehyde contents and a significant decrease in glutathione concentrations in ischemic rats compared with sham animals. Additional increase in malonaldehyde levels occurred during reperfusion in G-2 rats. TAP was similar in both groups denoting absence of systemic effects in this study. CONCLUSION: Torsion/detorsion of the spermatic cord for 3 h induces significant lipid peroxidation and reduction in glutathione content of the testis and is, therefore, a valid model for studying the oxidative stress effects of the ischemia/reperfusion injury in young rat testis.

Endoscopic Endonasal Surgery for Treatment of Pituitary Apoplexy: 16 Years of Experience in a Specialized Pituitary Center.

OBJECTIVE: Symptomatic pituitary apoplexy is a rare but life-threatening condition caused by sudden hemorrhage or infarction of a pituitary adenoma. In the current study, we aim to evaluate the clinical presentation, management, and clinical outcomes in a cohort of patients who were treated for this condition in our center in the last 16 years. METHODS: We performed a retrospective analysis of all patients who underwent endoscopic endonasal surgery for treatment of symptomatic pituitary apoplexy between 2001 and 2016 in our center. RESULTS: A total of 39 patients were included in the study, mean age of 54.9 years (range, 18-70 years) and mean follow-up 5.1 years (range, 0.6-16 years). Most of the patients had nonfunctioning adenomas (32 patients). Headache (89%), visual impairment (79%), and hypopituitarism (86%) were the most common preoperative findings. Surgical treatment led to gross total resection in 31 patients (79.4%). During follow-up, visual fields and oculomotor improvement was observed in 23 (74.1%) and 21 (67.7%) of the patients, respectively. Intractable headache also improved in all patients. Hypopituitarism was present in 77% of patients after surgery. In this series, no cerebrospinal fluid leak, vascular injury, or infection was observed. There was no postoperative mortality. CONCLUSIONS: The endoscopic endonasal transsphenoidal approach is an effective modality to treat pituitary apoplexy with a high rate of success and minimal risk in selected cases. Although reversion of preoperative visual deficits is often observed, hormonal deficits tend to persist, and require long-term hormonal therapy, even after successful endoscopic endonasal surgical resection.

Metabolic effects of l-alanyl-glutamine in burned rats.

Burn injury elicits a sustained hypermetabolic state characterized by accelerated hepatic synthesis of amino acids and proteolysis leading to negative nitrogen balance. This paper was aimed at studying the effects l-alanyl-glutamine (Ala-Gln) exogenous offer to rats submitted to thermal burn. Twenty-four anesthetized male Wistar rats were submitted to scald burn of dorsal skin (30% body surface). Eighteen and 42-h later rats were randomized to receive (by gavage) 2ml of water (G-1) or equal volume (0.5g/kg weight/day) of Ala-Gln solution (G-2). Tissue and blood samples were collected at the end of 24 and 48-h post-burn trauma (PBT). Blood concentrations of metabolites (glucose, pyruvate, lactate and ketone bodies) were similar in all groups. There were significant differences in tissue metabolites concentrations in Ala-Gln treated rats (G-2) compared to control (G-1) following scald injury. The administration of Ala-Gln to burned rats induces a fall ATP (muscle, healthy skin), pyruvate and ketone bodies (liver) concentrations 24-h PBT. It also induces significant increase of lactate (burned skin) 24-h and glucose (liver) 28/48-h PBT. Rise of tissue lactate concentrations may be due to enhanced anaerobic glycolysis resulting from increased availability of glutamate, derived from glutamine, with possible activation of the malate-aspartate shuttle.

Biomechanical properties of the biceps-labral complex submitted to mechanical stress.

PURPOSE: To determine biomechanical properties of the superior labrum-biceps tendon complex submitted to continuous and sudden mechanical strain. METHODS: Eighteen shoulder specimens from 15 unclaimed corpses, ages ranging from 20 to 40 years, were submitted to continuous or sudden tensile tests using 3 different traction machines. Shoulders presenting signs of degenerative diseases or preexisting traumatic lesions were excluded. RESULTS: Rupture of the distal portion of the long hand of the biceps occurred when stretching forces reached 290N in continuous traction and 384N in sudden traction. No labral-complex lesions were observed. CONCLUSION: Either a simple continuous or a sudden uniaxial traction of the arm do not play a role in the genesis of superior labrum anterior-posterior (SLAP) lesions in the shoulder joint.

Is subdiaphragmatic aortic cross-clamping a suitable model for spinal cord ischemia/reperfusion injury study in rats?

PURPOSE: To evaluate the efficacy of subdiaphragmatic aortic cross-clamping in an experimental model of ischemia/reperfusion injury of the spinal cord in albino rats. METHODS: Thirty-six male Wistar rats were randomized in two groups (n=18): G-1 (Sham) and G-2 (Ischemia/Reperfusion, I/R). G-2 rats were submitted to 30 min subdiafragmatic aortic cross-clamping. G-1 rats served as controls and were submitted to surgical trauma (laparotomy) without ischemia. Samples (spinal cord and arterial blood) were collected at the end of ischemic period and 10 (T-10) and 20 (T-20) min later in G-2 rats. Sham rats (G-1) samples were collected at the same time-points. Blood and tissue metabolites concentrations of pyruvate, lactate, glucose and medullary adenosine triphosphate (ATP) were assayed. RESULTS: Blood and tissue concentrations of pyruvate and glucose as well as lactate and medullary ATP were not different when comparing G1 to G2. Lactacemia was significantly elevated in G-2 compared with G-1 rats during reperfusion (T-10). CONCLUSION: Subdiaphragmatic aortic cord cross-clamping is not a suitable rat model for spinal cord ischemia/reperfusion injury study as it does not ensure changes in in vivo tissue metabolites concentrations similar to those found in tissues subjected to ischemia/reperfusion.

Effects of L-arginine oral supplements in pregnant spontaneously hypertensive rats.

PURPOSE: To evaluate the effects of L-arginine oral supplementation in spontaneously hypertensive pregnant rats (SHR). METHODS: Thirty SHR and ten Wistar-EPM-1 virgin female rats were used in the study. Before randomization, females were caged with males of the same strain (3:1). Pregnancy was confirmed by sperm-positive vaginal smear (Day 0). Wistar-EPM-1 rats served as counterpart control (C-1). SHR rats were randomized in 4 groups (n=10): Group Control 2, non-treated rats; Group L-Arginine treated with L-arginine 2%; Group Alpha-methyldopa treated with Alpha-methyldopa 33 mg/Kg; Group L-Arginine+Alpha-methyldopa treated with L-arginine 2%+Alpha-methyldopa 33 mg/Kg. L-arginine 2% solution was offered ad libitum in drinking water and Alpha-methyldopa was administered by gavage twice a day during the length of pregnancy (20 days). Blood pressure was measured by tail-cuff plethysmography on days 0 and 20. Body weight was measured on days 0, 10 and 20. Results were expressed as mean +/-SD (Standard Deviation). One-Way ANOVA/Tukey (or Kruskal-Wallis/Dunn, as appropriate) was used for group comparisons. Statistical significance was accepted as p<0.05. RESULTS: There was no significant weight gain in isolated L-arginine treated SHR. Mean blood pressure decreased in L-arginine-treated SLR compared with untreated-SHR rats. CONCLUSION: L-arginine oral supplementation reduces blood pressure in spontaneously hypertensive rats during pregnancy.

Short-term complementary and alternative medicine on quality of life in women with fibromyalgia.

BACKGROUND: Fibromyalgia (FMS) is a syndrome characterized by chronic widespread musculoskeletal pain, whose etiology is not completely understood. Different therapeutic approaches have been used with inconsistent results. This observation does not invalidate the continued search for alternative treatments aimed at improving quality of life (QoL) in FMS. OBJECTIVE: This study compared three classical traditional Chinese medicine (TCM) therapies: acupuncture (AC), electroacupuncture (EAC) and moxibustion (MX) in the management of pain and promotion of QoL in FMS patients. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: A preliminary, group-assigned, comparative study enrolled 30 women, mean age (46.90±9.24) years (range 20-60 years), who met the 1990 American College of Rheumatology criteria for FMS diagnosis and a pain-pressure threshold (PPT) < 4 kg/cm(2). The study was conducted in a teaching tertiary-care medical institution from May 2010 through April 2012. AC, EAC and MX were delivered for 30 min, once a week, for 8 weeks, bilaterally at Neiguan (PC6), Hegu (LI4), Yanglingquan (GB34), Sanyinjiao (SP6) and Taichong (LR3) acupoints. MAIN OUTCOME MEASURES: Each week, immediately before treatment and after treatment, subjects were tested for PPTs, Wong-Baker Faces Pain Scale (WBFPS; for pain intensity) and Medical Outcomes Study 36-item Short Form Health Survey (SF-36: for QoL). RESULTS: There was no significant improvement in pain or reduction of tender points in any of the groups studied, at the end of the 8th session. Significant improvement of QoL was perceived in vitality (after AC treatment) and in mental health (after EAC and MX treatments). CONCLUSION: TCM therapies (AC, EAC and MX) promoted an improvement in the QoL in two areas (vitality and mental health) in FMS women. Further large-scale clinical trials are required to confirm this effect.

Effects of L-alanyl-glutamine upon the blood and kidney biochemical parameters in the rat hind limb model of ischemia/reperfusion.

PURPOSE: To investigate the effects of l-alanyl-glutamine (Ala-Gln) intragastric administration upon blood and kidney metabolic parameters alterations in rats subjected to ischemia/reperfusion of hind limb. METHODS: Forty-eight male rats were randomized in 2 groups offered via gavage either saline 2.0 mL (G-1) or Ala-Gln solution 0.75 mgKg-1(G-2) once a day at 7 AM during 7 days. One-hour after the last gavage (Day 7) all rats were submitted to ether anesthesia, laparotomy and clamping of the left iliac artery for 3 h. Kidney and blood samples were collected at the end of ischemic period (3 h) and at 1-3-6 h during reperfusion period for metabolites (pyruvate, lactate, glucose and ketone bodies) enzymatic analysis. ATP was also assayed in kidney samples. RESULTS: Lactacemia and ketonemia were significantly increased in Ala-Gln treated rats during reperfusion. Kidney pyruvate concentrations were significantly decreased and tissue lactate concentrations were significantly increased during reperfusion (1 h and 3 h) in G-2 rats compared with respective controls. Glucose, ATP and ketone bodies concentrations were significantly increased in the kidney in L-Ala-Gln treated rats at 3 hours after reperfusion as compared to respective controls. CONCLUSIONS: Unilateral hind limb ischemia in L-Ala-Gln pre-treated rats may induce increased lactacemia and increased kidney lactate concentrations, indicating increased glycolytic activity in renal medulla and in other peripheral tissues. Higher ketonemia during reperfusion may reflect a possible increase in ketogenesis due to lower insulin plasma concentration hepatic signaling as a result of increased glucose oxidation in peripheral tissues, caused by the intra-gastric administration of glutamine dipeptide, suggesting also decreased insulin resistance.

A 16-week study to compare the effect of vildagliptin versus gliclazide on postprandial lipoprotein concentrations and oxidative stress in patients with type 2 diabetes inadequately controlled with metformin monotherapy.

BACKGROUND: Diabetes is closely linked with coronary artery disease, either by means of direct effects of hyperglycemia, or indirectly by its frequent association with dyslipidemia. Any treatment for diabetes that has beyond the capacity of reduce glycated hemoglobin, the propensity to improve lipid profile and reduce weight will bring many benefits to patients. METHOD: We compare the effects of vildagliptin with the gliclazide on lipid profile before and after a standardized meal test, on glycemic control and oxidative stress in diabetic patients using metformin without adequate glycemic control. This is a prospective study of 16 weeks with diabetic patients using metformin without adequate glycemic control. Patients were randomized to receive gliclazide 30-120 mg/day or vildagliptin 100 mg/day. RESULTS: 36 patients were randomized, with no loss of follow up. Regarding the lipid profile the difference observed at the end of the study was a higher HDL level in the vildagliptin group compared with gliclazide fasting (62.3 vs. 51.3 mg/dL, p = 0.021) and postprandial (62.9 vs. 51.1 mg/dL, p = 0.015). We also observed a variation of negative weight (decrease the end compared to the beginning) of the vildagliptin and a positive (increase) in the gliclazide (-0.3 vs. +1.4 Kg, p = 0.048). The decrease in A1c was lower in the vildagliptin group compared to gliclazide (-1.7 vs.-2.3 %, P = 0.031), however there was no difference in the number of patients reaching target glycated hemoglobin <7 % (50 vs. 61.1 %, p = 0.738). Only the group of vildagliptin presented at the end of the study compared to the beginning, decreased insulin values (599.6 vs.705, 59 pg/ml, p = 0.021), glucagon (46.6 vs.65, 2 pg/ml, p = 0.004) and the marker of oxidative stress TBARS (8.0 vs. 9.0 nmol MDA/ml, p = 0.035). CONCLUSION: Vildagliptin showed some advantages in addition to metformin in relation to addition of gliclazide. Patients treated with vildagliptin had a higher HDL at the end of the study, less variance in weight, reduced insulin and glucagon as well as reduction of oxidative stress.

Development of a subcutaneous endometriosis rat model.

PURPOSE: To present a rat model of subcutaneous endometriosis for the study of pathophysiology and the effects of drugs. METHODS: Fifty three-month-old female Wistar rats (Rattus norvergicus) were distributed into one control group and four treatment groups: estradiol (2.5; 5; 10 mg/kg s.c.), medroxyprogesterone acetate (0.5; 2; 5 mg/kg s.c.), triptorelin pamoate (0.18; 0.56 mg/kg s.c.) and acetylsalicylic acid (3 mg/kg per os). The animals were autoimplanted subcutaneously with 4x4-mm uterine fragments to induce endometriosis. The endometriomas were measured on days 1, 7, 14 and 21. The relative dry and wet weights of the endometrioma were used to evaluate response to the drug. Endometrial-like tissue was confirmed by histology. The greatest weight gain was observed on day 14 (relative wet weight: 29.1 ± 6.7 mg%, relative dry weight: 5.3 ± 0.9 mg %). Treatments were administered between day 5 and day 14. RESULTS: The relative wet weight of the hemiuterus in the 10 mg/kg estradiol group differed significantly from control and the other two estradiol groups (p=0.0001). In the medroxyprogesterone acetate group the weight decreased significantly but this decrease was not dose-dependent. Weight reduction was also significant in the triptorelin pamoate and the acetylsalicylic acid groups. CONCLUSION: The model of subcutaneous endometriosis is reproducible, low-cost and easy to perform, and suitable for the study of pathophysiology and the effects of drugs.

Effect of propranolol on capsular reaction around silicone implants in guinea pigs.

PURPOSE: To evaluate the effect of propranolol on capsular architecture around silicone implants by measuring the inflammation, capsular thickness, and collagen fiber density, using a guinea pig experimental model. METHODS: Thirty six adult male guinea pigs randomly divided into two groups (n=18) were used. Each one received a silicone implant with textured-surface. The capsular tissue around implants from untreated or treated animals with the beta-adrenoceptor antagonist propranolol (10 mg/kg, dissolved in daily water) were analyzed for inflammation by histological scoring, capsular thickness by computerized histometry, and collagen fibers type I and Type III density by picrosirius polarization at different time points (7, 14 or 21 days after silicone implantation). RESULTS: Propranolol treatment reduced inflammation and impaired capsular thickness and delayed collagen maturation around the textured implant. CONCLUSION: Propranolol reduces the risk of developing capsular contracture around silicone implants with textured surface.

Fructo-oligosaccharide effects on serum cholesterol levels. An overview.

PURPOSE: To address the effects of fructooligosaccharides (FOS) intake on serum cholesterol levels. METHODS: We performed a search for scientific articles in MEDLINE database from 1987 to 2014, using the following English keywords: fructooligosaccharides; fructooligosaccharides and cholesterol. A total of 493 articles were found. After careful selection and exclusion of duplicate articles 34 references were selected. Revised texts were divided into two topics: "FOS Metabolism" and "FOS effects on plasma cholesterol." RESULTS: The use of a FOS diet prevented some lipid disorders and lowered fatty acid synthase activity in the liver in insulin-resistant rats. There was also reduction in weight and total cholesterol in beagle dogs on a calorie-restricted diet enriched with short-chain FOS. Another study found that 2g FOS daily consumption increased significantly serum HDL cholesterol levels but did not ensure a significant reduction in levels of total cholesterol and triglycerides.. Patients with mild hypercholesterolemia receiving short-chain FOS 10.6g daily presented no statistically significant reduction in serum cholesterol levels. However, when FOS was offered to patients that changed their lifestyle, the reduction of LDL cholesterol and steatosis was higher. CONCLUSIONS: Fructooligosaccharides intake may have a beneficial effect on lipid metabolism and regulation of serum cholesterol levels in individuals that change their lifestyle. FOS supplementation use in diets may therefore be a strategy for lowering cholesterol.