Microdialysis study of striatal dopamine in MPTP-hemilesioned rats challenged with apomorphine and amphetamine

Motor impairments of Parkinson`s disease (PD) appear only after the loss of more than 70% of the DAergic neurons of the substantia nigra pars compacta (SNc). An earlier phase of this disease can be modeled in rats that received a unilateral infusion of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrindine (MPTP) into the SNc. Though these animals do not present gross motor impairments, they rotate towards the lesioned side when challenged with DAergic drugs, like amphetamine and apomorphine. The present study aimed to test whether these effects occur because the drugs disrupt compensatory mechanisms that keep extracellular levels of dopamine in the striatum (DA(E)) unchanged. This hypothesis was tested by an in vivo microdialysis study in awake rats with two probes implanted in the right and left striatum. Undrugged rats did not present turning behaviour and their basal DA(E) did not differ between the lesioned and sham-lesioned sides. However, after apomorphine treatment, DA(E) decreased in both sides, but to a larger extent in the lesioned side at the time the animals started ipsiversive turning behaviour. After amphetamine challenge, DA(E) increased in both sides, becoming significantly higher in the non-lesioned side at the time the animals started ipsiversive turning behaviour. These results are in agreement with the hypothesis that absence of gross motor impairments in this rat model of early phase PD depends on maintenance of extracellular DA by mechanisms that may be disrupted by events demanding its alteration to higher or lower levels. (C) 2010 Elsevier B.V. All rights reserved.

Cardiovascular, metabolic and hormonal responses to the progressive exercise performed to exhaustion in patients with type 2 diabetes treated with metformin or glyburide

Objectives: To evaluate the effects of Metformin and Glyburide on cardiovascular, metabolic and hormonal parameters during progressive exercise performed to exhaustion in the post-prandial state in women with type 2 diabetes (T2DM). Design and Methods: Ten T2DM patients treated with Metformin (M group), 10 with Glyburide (G group) and 10 age-paired healthy subjects exercised on a bicycle ergometer up to exercise peak. Cardiovascular and blood metabolic and hormonal parameters were measured at times -60 min, 0 min, exercise end, and at 10 and 20 minutes of recovery phase. Thirty minutes before the exercise, a standard breakfast was provided to all participants. The diabetic patients took Metformin or Glyburide before or with meal. Results: Peak oxygen uptake (VO2) was lower in patients with diabetes. Plasma glucose levels remained unchanged, but were higher in both diabetic groups. Patients with diabetes also presented lower insulin levels after meals and higher glucagon levels at exercise peak than C group. Serum cortisol levels were higher in G than M group at exercise end and recovery phase. Lactate levels were higher in M than G group at fasting and in C group at exercise peak. Nor epinephrine, GH and FFA responses were similar in all 3 groups. Conclusion: Progressive exercise performed to exhaustion, in the post-prandial state did not worsen glucose control during and after exercise. The administration of the usual dose of Glyburide or Metformin to T2DM patients did not influence the cardiovascular, metabolic and hormonal response to exercise.

The soybean concentrated extract proliferates the vagina of adult rats

Objective: The aim of this study was to evaluate changes induced on the vagina of ovariectomized rats after treatment with soybean concentrated extract or conjugated equine estrogens and the association of both drugs. Methods: We conducted an experimental study with 50 ovariectomized rats that were randomly divided into five equal groups of 10 animals: GI received vehicle, GII received soybean concentrated extract 46 mg/kg per day, GIII received soybean concentrated extract 120 mg/kg per day, GIV received conjugated equine estrogens 50 mu g/kg per day, and GV received conjugated equine estrogens 50 mu g/kg and soybean concentrated extract 46 mg/kg per day. The substances were administered by gavage during 21 consecutive days. After that, the animals were killed under anesthesia and the vagina was removed for histological and immunohistochemical analysis. Data were initially submitted to analysis of variance. Whenever a significant difference was detected, the study was complemented with the Tukey-Kramer test for multiple comparisons. Results: GII did not show any differences on the vaginal epithelium or collagen compared with GI. GIII presented an increase in vaginal epithelium and collagen amount. GIV had the highest amount of collagen and the signals of vaginal proliferation. GV did not show any additional effect compared with GIV. Conclusions: Our data suggest that a high dose of isoflavone-rich soy extract may have positive effects on the vaginal structures of ovariectomized rats, but this action is less than that of estrogen treatment on vaginal thickness. In addition, soy extract may not block the estrogen effect on vaginal tissue.

Effects of metoclopramide-induced hyperprolactinemia on the prolactin receptor of murine endometrium

Objective: To evaluate the effects of metoclopramide-induced hyperprolactinemia, on the prolactin receptor of murine endometrium. Design: Experimental study using the RNA extraction to detect tissue prolactin recepter isoforms by reverse-transcriptase polymerase chain reaction (RT-PCR). Setting: University-based laboratory. Animal(s): Seventy-two female swiss albino mice (Mus musculus), approximately 100 days old, were divided into six 12-animal groups: (Cl) nonoophorectomized mice given vehicle; (GII) nonoophorectomized mice treated with metoclopramide; (Gill) oophorectomized mice treated with metoclopramide; (GIV)oophorectomized mice treated with metoclopramide and 17 beta-estradiol; (GV) oophorectomized mice treated with metoclopramide and micronized progesterone; (GVI) oophorectomized mice treated with metoclopramide and a solution of 17 beta-estradiol and micronized progesterone. Intervention(s): Drugs were administered for 50 days. Following euthanasia, the middle portions of the uterine horns were removed, sectioned, and immediately frozen for RT-PCR procedures. Blood was collected for the dosage of prolactin and serum estrogen and progesterone using radioimmune assay. Main Outcome Measure(s): Identification of uterine prolactin receptor isoforms: Result(s): The PRL receptor and its isoform L were identified only in GI (control group) and GII (metoclopramide), the two groups with nonoophorectomized animals. The amount of PRL receptor mRNA and that of its isoform L from GII were the largest. No other isoforms of the prolactin receptor were identified in any of the groups. Conclusion(s): Our results suggest that replacement of estrogen and progestin may not increase the mRNA of endometrial PRL receptor in metoclopromide-induced hyperprolactinemia in rats after castration. (Fertil Steril (R) 2010;93:1643-9. (C)2010 by American Society for Reproductive Medicine.)

Effects of melatonin on the endometrial morphology and embryo implantation in rats

Objective: To determine the effects of melatonin on rat endometrium morphology and embryo implantation. Design: Experimental study. Setting: Federal University of Sao Paulo, Brazil. Animal(s): Forty female rats. Intervention(s): GI: control, GII: sham-operated, GIII: pinealectomized, and GIV: pinealectomized rats that received melatonin during 3 months. The GI, GII, and Gin groups received the vehicle of melatonin (NaCl + ethanol). At the end of the treatment, the animals were killed during the estrous phase; the uterus was removed for morphometric analysis. Urine was collected for 6-sulfatoxymelatonin. Blood was collected for estrogen (E) and progesterone (P) level determinations. In a second experiment, female rats were used to evaluate the endometrial embryo implantation. Main Outcome Measure(s): Endometrial morphology and embryo implantation. Result(s): Gin presented the highest values for endometrial area and thickness index, number of endometrial glands, and eosinophils. The number of vessels of groups I, II, and IV was fewer than that of Gin. The highest number of eosinophils was detected in Gin in comparison to other groups. The implantation rate in Gin was the lowest of all groups. This implantation rate was significantly increased and restored toward normal in GIV. Conclusion(s): Our data suggested that, in nonphotoperiodic animals such as rats, melatonin may positively affect the endometrial morphology and improve embryo implantation.

Ultrastructural evaluation of gingival glycosaminoglycans in ovariectomized rats: Effects of steroid hormone therapy

Background/Aims: To evaluate the behavior of glycosaminoglycans (GAGs) in rat gingiva and the effects of lack of sexual steroids and the hormonal therapy with estrogen and dexamethasone (DEX). Methods: 40 female rats were divided into four groups: GI: animals in permanent estrus; GII: ovariectomized (OVX) animals + vehicle; GIII: OVX animals treated with 17 beta-estradiol benzoate (10 mu g/kg), and GIV: OVX animals treated with 17 beta-estradiol benzoate (10 mu g/kg) + DEX (3 mg/kg). After treatment, the gingiva was removed and its GAGs content was evaluated by electronic microscopy after stained by cuprolinic blue technique. Results: The electron-microscopic data showed that low values of chondroitin sulfate were found in castrated animals (35.05 +/- 3.58%) compared to other groups (GI: 41.17 +/- 1.13; GIII: 48.04 +/- 2.60; GIV: 49.09 +/- 2.68%). In contrast, the amount of dermatan sulfate in GII (57.70 +/- 2.50%) was higher than in the other groups (GI: 46.12 +/- 1.30; GIII: 42.65 +/- 2.98; GIV: 42.68 +/- 5.43%). Conclusions: GAGs may be influenced by estradiol, and DEX did not seem to antagonize the role of estradiol in the GAGs of gingiva. The histotypical structure of gingiva is related to the amount of chondroitin sulfate. Consequently, the estrogen therapy may be important for gingival health. Copyright (C) 2007 S. Karger AG, Basel.

Ethnicity and Arterial Stiffness in Brazil

BACKGROUND The impact of increased central arterial stiffness as a predictor of morbidity and mortality, independently of other cardiovascular (CV) risk factors, has been established. The main aim of the present work was to investigate the association of ethnicity on arterial stiffness in different ethnic groups from the Brazilian population. METHODS A total of 1,427 individuals from the general population were randomly selected from the Vitoria City metropolitan area and 588 Amerindians from a native community in Brazil. The ethnicity of the general population was classified by a standard questionnaire as Caucasian descent, African descent, or Mulattos (considered racially mixed subjects). Pulse wave velocity (PWV) was measured with a noninvasive automatic device (Complior, Colson; Garges les Gonesses, France). RESULTS Hemodynamic data of PWV, systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean blood pressure (MBP) was higher in African descent individuals than in the other groups (P < 0.001). These results were still observed after adjustment for age and mean arterial pressure (P < 0.001). In addition, studying only normotensive individuals, PWV adjusted levels were higher in African descent individuals, and lower in Amerindians when compared with other ethnic groups (P < 0.01), showing, without the possible confounder effects of time and severity of hypertension or medication use, that PWV is associated with ethnicity in our population. CONCLUSION The study of different ethnic groups from a highly admixtured population was able to demonstrate an association between ethnicity and arterial stiffness.

APOE polymorphism is associated with lipid profile, but not with arterial stiffness in the general population

Background: Cardiovascular diseases (CVD) are the main cause of death and disability in developed countries. In most cases, the progress of CVD is influenced by environmental factors and multifactorial inheritance. The purpose of this study was to investigate the association between APOE genotypes, cardiovascular risk factors, and a noninvasive measure of arterial stiffness in the Brazilian population. Methods: A total of 1493 urban Brazilian individuals were randomly selected from the general population of the Vitoria City Metropolitan area. Genetic analysis of the APOE polymorphism was conducted by PCR-RFLP and pulse wave velocity analyzed with a noninvasive automatic device. Results: Age, gender, body mass index, triglycerides, creatinine, uric acid, blood glucose, blood pressure phenotypes were no different between epsilon 2, epsilon 3 and epsilon 4 alleles. The epsilon 4 allele was associated with higher total-cholesterol (p < 0.001), LDL-C (p < 0.001), total-cholesterol/HDL-C ratio (p < 0.001), LDL/HDL-C ratio (p < 0.001), lower HDL-C values (p < 0.001) and higher risk to obesity (OR = 1.358, 95% CI = 1.019-1.811) and hyperuricemia (OR = 1.748, 95% CI = 1.170-2.611). Nevertheless, pulse wave velocity (p = 0.66) measures were no different between genotypes. The significant association between APOE genotypes and lipid levels persisted after a 5-year follow-up interval, but no interaction between time and genotype was observed for lipids longitudinal behavior. Conclusion: The epsilon 4 allele of the APOE gene is associated with a worse lipid profile in the Brazilian urban population. In our relatively young sample, the observed effect of APOE genotype on lipid levels was not translated into significant effects in arterial wall stiffness.

Group psychotherapy: An additional approach to burning mouth syndrome

Introduction: Glossodynia or burning mouth syndrome (BMS) is a common and poorly understood disorder. Its treatment is uncertain. Otherwise, there is some evidence of the importance of psychological factors in the genesis of this disease. Objectives: Verify the usefulness of group psychotherapy as an adjuvant therapeutic method in the treatment of BMS. Casuistics and Methods: The study group consisted of 64 consecutive patients with a clinical diagnosis of BMS seen at the Stomatology Outpatient Clinic, ENT Department, Sao Paulo University Medical School, between May 2002 and May 2007. All the patients were submitted to physical examination, laboratorial screening tests, psychological assessment (Crown-Crisp Experimental Inventory), and answered a short form of the McGill Pain Questionnaire. Only 44 patients who did not show any abnormality in the protocol exams entered the study. Twenty-four of them underwent group psychotherapy. Twenty patients received placebo. Chi-square test was applied to compare the results of treatment with or without psychotherapy. Results: There were 15 men and 29 women in the study group. Tongue burning was the main complaint of the patients. Improvement of symptoms was reported by 17 (70.8%) of the patients undergoing psychotherapy, while among those who did not eight (40%) had improvement of symptoms (P=.04). Conclusion: Psychological assessment demonstrated a close correlation between symptoms and psychological factors, suggesting that group psychotherapy is an important alternative to conventional treatment methods. (C) 2009 Elsevier Inc. All rights reserved.

Molecular Characterization of Patients with X-linked Hyper-IgM Syndrome: Description of Two Novel CD40L Mutations

Type 1, X-linked Hyper-IgM syndrome (HIGM1) is caused by mutations in the gene encoding the CD154 protein, also known as CD40 ligand (CD40LG). CD40L is expressed in activated T cells and interacts with CD40 receptor expressed on B lymphocytes and dendritic cells. Affected patients present cellular and humoral immune defects, with infections by intracellular, opportunistic and extracellular pathogens. In the present study we investigated the molecular defects underlying disease in four patients with HIGM1. We identified four distinct CD40L mutations, two of them which have not been previously described. P1 harboured the novel p.G227X mutation which abolished CD40L expression. P2 had a previously described frame shift deletion in exon 2 (p.I53fsX65) which also prevented protein expression. P3 demonstrated the previously known p.V126D change in exon 4, affecting the TNF homology (TNFH) domain. Finally, P4 evidenced the novel p.F229L mutation also located in the TNFH domain. In silico analysis of F229L predicted the change to be pathological, affecting the many hydrophobic interactions of this residue. Precise molecular diagnosis in HIGM syndrome allows reliable detection of carriers, making genetic counselling and prenatal diagnosis possible.

Routine abdominal drains after Roux-en-Y gastric bypass: a prospective evaluation of the inflammatory response

Background: Despite the extensive published data regarding the use of drains in surgery, it is still controversial. Most bariatric surgeons use drains as routinely. However, drains have sometimes have been shown to be unhelpful and even to increase the anastomotic leak rates. The purpose of the present study was to evaluate the peritoneal inflammatory response in the presence of a drain left in place until the seventh postoperative day after bariatric surgery. Methods: All patients who underwent open Roux-en-Y gastric bypass from February 2007 to August 2008 were prospectively evaluated. A 24F Blake drain was left in place for 7 days. The peritoneal effluent from the drain was collected for the determination of cytokine levels and for microbiologic analysis. Results: A total of 107 obese patients were studied. A marked increase in the levels of tumor necrosis factor-alpha and interleukin-1 beta was observed by the seventh postoperative day, even in patients without any abdominal complications. Bacterial contamination of the peritoneal effluent was also demonstrated. Conclusion: The results of our study have shown that at 7 days after surgery, a marked peritoneal inflammatory response and bacterial contamination are present. These findings could have resulted from the use of the drain for 7 postoperative days. (Surg Obes Relat Dis 2010;6:648-652.) (C) 2010 American Society for Metabolic and Bariatric Surgery. All rights reserved.

Early Identification of Infectious Complications in Bariatric Surgery by the Determination of Peritoneal and Systemic Cytokines

Obesity has become a global epidemic and bariatric surgery is one of the therapeutic tools to deal with it. Postoperative complications can occur, such as staple line dehiscence and anastomotic leaks, leading to increased patient mortality. The diagnosis of these complications is frequently difficult. The objective of the present study was to determine whether peritoneal and systemic cytokines could early detect those complications. All patients who underwent open Roux-en-Y gastric bypass from February 2007 to August 2008 were prospectively evaluated. Blood and peritoneal effluent from the drain were collected for the determination of cytokine levels. We also evaluated the clinical signs and the leukograms of the patients. A total of 107 obese patients were studied. Ninety patients had no complications; 17 had at least one infectious complication which include five cases of staple line dehiscence. Until the third postoperative day, the vital signs and the leukogram did not predict the onset of infectious complications, but the cytokines (interleukin-1 beta and interleukin-6) were early markers of these complications. Cytokines are good predictors of poor postoperative evolution in bariatric surgery since peritoneal cytokines diagnose better these infectious complications even before changes in blood count and before the occurrence of clinical manifestations.

Cannabidiol decreases bone resorption by inhibiting RANK/RANKL expression and pro-inflammatory cytokines during experimental periodontitis in rats

Cannabidiol (CBD) is a cannabinoid component from Cannabis sativa that does not induce psychotomimetic effects and possess anti-inflammatory properties. In the present study we tested the effects of CBD in a periodontitis experimental model in rats. We also investigated possible mechanisms underlying these effects. Periodontal disease was induced by a ligature placed around the mandible first molars of each animal. Male Wistar rats were divided into 3 groups: control animals; ligature-induced animals treated with vehicle and ligature-induced animals treated with CBD (5 mg/kg, daily). Thirty days after the induction of periodontal disease the animals were sacrificed and mandibles and gingival tissues removed for further analysis. Morphometrical analysis of alveolar bone loss demonstrated that CBD-treated animals presented a decreased alveolar bone loss and a lower expression of the activator of nuclear factor-kappa B ligand RANKL/RANK. Moreover, gingival tissues from the CBD-treated group showed decreased neutrophil migration (MPO assay) associated with lower interleukin (IL)-1 beta and tumor necrosis factor (TNF)-alpha production. These results indicate that CBD may be useful to control bone resorption during progression of experimental periodontitis in rats. Crown Copyright (C) 2008 Published by Elsevier B.V. All rights reserved.

Morphologic evaluation and expression of matrix metalloproteinases-2 and 9 and nitric oxide during experimental periodontal disease in rat

The immunopathologic and inflammatory mechanisms involved in periodontal disease (PD) include the participation of host resident, inflammatory cells and chemical mediators. Metalloproteinases (MMPs) and nitric oxide (NO) play essential role in extracellular matrix turnover of periodontal tissue destruction. In this study, by means of RT-PCR through semi-quantitative densitometric scanning methods, the expression of MMPs -2 and -9 and inducible NO synthase (iNOS) was temporally and spatially investigated during the destructive mechanisms of experimentally induced PD in rats. Samples from different periods were microscopically analyzed and compared with the contralateral side (control). Our results showed significant expression of MMP-9 and iNOS in tissues affected by PD, as compared with controls, three days after PD induction, simultaneously with the beginning of alveolar bone loss. At 7 days post induction, only the MMP-9 mRNA presented a significantly higher expression, as compared with the respective controls. Thus, in the rat ligature-induced PD, MMP-9 and iNOS might importantly participate in the early stages of the disease, including inflammatory cell migration, tissue destruction and alveolar bone resorption. Also, we may suggest that the exuberant presence of PMNs may be related to the important expression of iNOS and MMP-9 found at 3 days post induction.