Immunoexpression of angiogenesis and proliferation markers in patients treated with cyclosporin A

In the present immunohistochemical study, the expression of vascular endothelial growth factor, nitric oxide synthase 1 and 3, and Ki-67 in the gingival tissues of renal transplant patients treated with cyclosporin A was assessed. Gingival overgrowth (GO) frequently occurs in transplant patients receiving immunosuppressive drugs such as cyclosporine and this gingival inflammation might play an important role in the pathogenesis of drug-induced GO. Twenty-eight human gingival biopsies were taken from healthy patients with chronic periodontitis (N.=14 control group), and from renal transplant recipients treated with cyclosporin A (N.=14 test group). The retrieved specimens were immunohistochemically processed and stained for vascular endothelial growth factor, nitric oxide synthase 1 and 3, and Ki-67. The levels of vascular endothelial growth factor, nitric oxide synthase 1 and 3, and Ki-67 were found to be significantly different among groups (P>0.001), with patients treated with cyclosporin A showing higher levels of all the analyzed markers compared to control group. In summary, the data from this pilot study suggests that the investigated factors have a role in the inflammation processes associated to immunosuppressive therapy. However, further studies with a larger sample population need to be conducted for an exhaustive knowledge of the mechanisms leading to GO.

Ayahuasca alters structural parameters of the rat aorta

Ayahuasca is a hallucinogenic brew traditionally used by Northwestern Amazonian indigenous groups for therapeutic purposes. It is prepared by the decoction of Banisteriopsis caapi with the leaves of Psychotria viridis. Banisteriopsis caapi contains β-carbolines that are inhibitors of monoamine oxidase and P. viris is rich in dimethyltryptamine, a 5-HT(1A/2A/2C) agonist. Acute ayahuasca administration produces moderate cardiovascular effects in healthy volunteers, but information regarding long-term use is lacking. This study investigated the effects of ayahuasca (2-4 mL/kg) in the rat aorta after acute and chronic (14 days) administration. Ayahuasca caused flattening and stretching of vascular smooth muscle cells and changes in the arrangement and distribution of collagen and elastic fibers. Chronic treatment with the higher dose significantly increased media thickness and the ratio of media thickness to lumen diameter. More research is needed on the cardiovascular function of long-term ayahuasca consumers.

Immunolocalization of aquaporins 1 and 9 in the ram efferent ducts and epididymis

Aquaporins (AQPs) are essential membrane protein channels for the transport of water across membranes. Fluid movement in the epididymis is important for modulation of the luminal environment, in which sperm mature and reside. This study was designed to understand the morphology and localization of AQPs in ram efferent ducts (ED) and epididymis. For this purpose, the epididymis of seven animals were removed for histologic and immunohistochemical analyses. AQP1 immunoreactivity was observed in the apex of the ED, and AQP9 was found adjacent to the nuclei of the epithelial cells of the ED. The epithelial lining of ram epididymis is pseudostratified columnar and presents principal, basal, apical and narrow cells. In the initial segment (IS), a moderate reaction for AQP1 was observed in the apical cytoplasm of epithelial cells. An intense reactivity for AQP1 was noted over the microvilli of principal cells and in spermatozoa in the caput. In the corpus and cauda, AQP1 was noted only over the endothelial cells of vascular channels located in intertubular spaces. A weak-to-moderate reaction for AQP9 was observed in the nuclei of epithelial cells in the IS, caput and corpus of the epididymis. In the cauda, an intense reaction to AQP9 was observed in the epithelial border. In the IS, caput and corpus, the reactivity for AQP9 differed from those observed in domestic animals. The cauda showed a pattern similar to that previously described. These results indicate that AQPs 1 and 9 have reversed locations and roles in rams, suggesting activity variations related with fluid and solute absorption throughout the epididymis.

An isolated phlebolith on the lip: an unusual case and review of the literature

Background. Calcified thrombi are a common finding, especially in the pelvic veins. There are generally multiple thrombi, and they are generally associated with vascular malformations. Design. Herein we report a rare case of a single labial phlebolith, not associated with any other vascular lesion. We aim to alert clinicians to the possibility of the occurrence of vascular thrombi in the mouth and to describe the clinical and histological characteristics of such lesions in order to simplify the diagnosis and treatment. Furthermore, we have reviewed the English-language literature published since 1970 reporting oral (including masticatory muscles) phleboliths. Results. Twenty-nine cases of phleboliths have been reported in the literature since 1970. Only three of the reported phleboliths were solitary and not associated with other vascular lesions, as in the case presented here. Conclusion. Although phleboliths not associated with other vascular lesions are not common, clinicians should be aware of the existence of this pathology and include it as differential diagnosis of oral lesions.

Apoptosis and reduced microvascular density of the lamina propria during tooth eruption in rats

During tooth eruption, structural and functional changes must occur in the lamina propria to establish the eruptive pathway. In this study, we evaluate the structural changes that occur during lamina propria degradation and focus these efforts on apoptosis and microvascular density. Fragments of maxilla containing the first molars from 9-, 11-, 13- and 16-day-old rats were fixed, decalcified and embedded in paraffin. The immunohistochemical detection of vascular endothelial growth factor (VEGF), caspase-3 and MAC387 (macrophage marker), and the TUNEL method were applied to the histological molar sections. The numerical density of TUNEL-positive cells and VEGF-positive blood vessel profiles were also obtained. Data were statistically evaluated using a one-way anova with the post-hoc Kruskal-Wallis or Tukey test and a significance level of P ≤ 0.05. Fragments of maxilla were embedded in Araldite for analysis under transmission electron microscopy (TEM). TUNEL-positive structures, fibroblasts with strongly basophilic nuclei and macrophages were observed in the lamina propria at all ages. Using TEM, we identified processes of fibroblasts or macrophages surrounding partially apoptotic cells. We found a high number of apoptotic cells in 11-, 13- and 16-day-old rats. We observed VEGF-positive blood vessel profiles at all ages, but a significant decrease in the numerical density was found in 13- and 16-day-old rats compared with 9-day-old rats. Therefore, the establishment of the eruptive pathway during the mucosal penetration stage depends on cell death by apoptosis, the phagocytic activity of fibroblasts and macrophages, and a decrease in the microvasculature due to vascular cell death. These data point to the importance of vascular rearrangement and vascular neoformation during tooth eruption and the development of oral mucosa.

Anatomical description of arterial segment of spleen of deer

The anatomosurgical segmentation of the arteries of the spleen was studied in 31 deer of the species Mazama gouazoubira and Blastocerus dichotomus by means of vascular injection with latex and vinyl acetate and radiographic examination. The arteria lienalis penetrated through the hilus lienis in 87% of the cases, whereas an extrahilar artery was present in the other cases. An extraparenchymal division of the lineal artery into two, three or four segmental arteries was observed in 74% of the cases. Anastomoses between intraparenchymal arterial branches were rare and of a reduced calibre.

Occluded Tunneled Venous Catheter in Hemodialysis Patients: Risk Factors and Efficacy of Alteplase

Thrombosis of tunneled central venous catheters (CVC) in hemodialysis (HD) patients is common and it can lead to the elimination of vascular sites. This study aimed to evaluate the incidence of thrombotic obstruction of tunneled CVC in HD patients and the efficacy of occlusion treatment with alteplase use, and identify factors associated with thrombotic occlusion. It was a prospective cohort study performed in two centers which evaluated the diagnosis and treatment of thrombotic occlusion of CVC in HD patients for 24 consecutive months. The catheter occlusion was defined as the difficulty infusing or withdrawing fluid from their paths. Alteplase dose was infused to fill the lumen of the occluded catheter and remained for 50 min. As there was no obstruction of the catheter, the procedure was repeated. Three hundred and thirty-nine CVC in 247 patients were evaluated and followed, totalling 67 244 CVC-days. One hundred fifty-seven patients had only one CVC, 88 patients had two CVC during the study, and two patients had three CVC. The median age was 58 (47–66) years, patients were predominantly men (54%), with diabetic nephropathy as the main cause of chronic kidney disease (44%), the internal jugular vein as the main site of implantation (82%), and duration of dialysis before CVC implantation of 119 (41.5 to 585.5) days. Eight hundred and fifteen occlusion episodes were diagnosed (12 episodes/1000 CVC-days), with primary success with alteplase in 596 episodes (77%) and secondary in 81 cases (10%). In 99 episodes (13%), success was not achieved after the second dose of alteplase. Two hundred and thirty CVC were removed during the study and the removal causes were arteriovenous fistula use in 88 patients (38.3%), infectious and mechanical complications in 89 (38.7%) and 21 (9.1%), respectively, and others (transplantation, transfer, or death) in 32 patients (13.9%). Adverse effects were also not observed. In the multivariate analysis, we identified the greatest number of days with CVC (OR = 1.02, CI = 1.01–1.04, P = 0.004), the presence of diabetes (OR = 1.560, CI = 1.351–1.894, P = 0.015), and exit site infection (ESI) (OR = 1.567 CI = 1347–1926, P = 0.023) as factors associated with obstruction. Thrombotic occlusion showed frequent mechanical complication in CVC of HD patients. We observed 12 episodes of obstruction per 1000 CVC-days, with a high success rate after alteplase use (87%). In the multivariate analysis, the time with CVC, the presence of diabetes, and ESI were identified as variables associated with thrombotic obstruction.

A possible increase of activity of endothelial l-arginine/nitric oxide pathway in aortas of diet-induced obesity rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Pleural tuberculosis: is radiological evidence of pulmonary-associated disease related to the exacerbation of the inflammatory response?

OBJECTIVE: Pleural tuberculosis is the most frequently occurring form of extra pulmonary disease in adults. In up to 40% of cases, the lung parenchyma is concomitantly involved, which can have an epidemiological impact. This study aims to evaluate the pleural and systemic inflammatory response of patients with pleural or pleuropulmonary tuberculosis. METHODS: A prospective study of 39 patients with confirmed pleural tuberculosis. After thoracentesis, a high resolution chest tomography was performed to evaluate the pulmonary involvement. Of the 39 patients, 20 exhibited only pleural effusion, and high resolution chest tomography revealed active associated-pulmonary disease in 19 patients. The total protein, lactic dehydrogenase, adenosine deaminase, vascular endothelial growth factor, interleukin-8, tumor necrosis factor-alpha, and transforming growth factor-beta(1) levels were quantified in the patient serum and pleural fluid. RESULTS: All of the effusions were exudates with high levels of adenosine deaminase. The levels of vascular endothelial growth factor and transforming growth factor-beta(1) were increased in the blood and pleural fluid of all of the patients with pleural tuberculosis, with no differences between the two forms of tuberculosis. The tumor necrosis factor-alpha levels were significantly higher in the pleural fluid of the patients with the pleuropulmonary form of tuberculosis. The interleukin-8 levels were high in the pleural fluid of all of the patients, without any differences between the forms of tuberculosis. CONCLUSION: Tumor necrosis factor-alpha was the single cytokine that significantly increased in the pleural fluid of the patients with pulmonary involvement. However, an overlap in the results does not permit us to suggest that cytokine is a biological marker of concomitant parenchymal involvement. Although high resolution chest tomography can be useful in identifying these patients, the investigation of fast acid bacilli and cultures for M. tuberculosis in the sputum is recommended for all patients who are diagnosed with pleural tuberculosis.

Supracerebellar transtentorial approach-resection of the tentorium instead of an opening-to provide broad exposure of the mediobasal temporal lobe: anatomical aspects and surgical applications Clinical article

Object. The aim of this study was to describe the surgical anatomy of the mediobasal aspect of the temporal lobe and the supracerebellar transtentorial (SCTT) approach performed not with an opening, but with the resection of the tentorium, as an alternative route for the neurosurgical management of vascular and tumoral lesions arising from this region. Methods. Cadaveric specimens were used to illustrate the surgical anatomy of the mediobasal region of the temporal lobe. Demographic aspects, characteristics of lesions, clinical presentation, surgical results, follow-up findings, and outcomes were retrospectively reviewed for patients referred to receive the SCTT approach with tentorial resection. Results. Ten patients (83%) were female and 2 (17%) were male. Their ages ranged from 6 to 59 years (mean 34.5 +/- 15.8 years). All lesions (3 posterior cerebral artery aneurysms, 3 arteriovenous malformations, 3 cavernous malformations, and 3 tumors) were completely excluded or resected. After a mean follow-up period of 143 months (range 10-240 months), the mean postoperative Glasgow Outcome Scale score was 4.9. Conclusions. Knowledge of the surgical anatomy provides improvement for microsurgical approaches. The evolution from a small opening to a resection of the tentorium absolutely changed the exposure of the mediobasal aspect of the temporal lobe. The SCTT approach with tentorial resection is an excellent alternative route to the posterior part of mediobasal aspect of the temporal lobe, and it was enough to achieve the best neurosurgical management of tumoral and vascular lesions located in this area. (http://thejns.org/doi/abs/10.3171/2011.12.JNS111256)

Impact of comorbid migraine on the clinical course of bipolar disorder

Background: Recent evidence suggests an association between migraine and bipolar disorder (BD), although the impact of this association in the clinical course of BD is relatively unknown. Objective: This study aimed to compare 2 groups of individuals with BD (with vs without comorbid migraine) and evaluate differences in severity of clinical course. Methods: Three hundred thirty-nine adults with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition defined bipolar or II disorder were enrolled and divided into 2 groups: with and without comorbid migraine. Demographic and clinical data were obtained using standardized interviews. Results: Patients with comorbid migraines had more mood episodes, especially those with depressive polarity. In addition, comorbid migraine was associated with a higher prevalence of psychiatric and general medical comorbidities. Differences between the 2 groups in number of lifetime hospitalizations for depression/mania, rates of rapid cycling, and history of suicide attempts were not observed after Bonferroni correction. Conclusions: Comorbid migraine seems to be associated with poor outcomes in BD. Additional studies should be conducted to investigate shared vulnerabilities and pathophysiologic mechanisms as well as treatment optimization of both illnesses. (C) 2012 Elsevier Inc. All rights reserved.

Morphology and Anatomy of Stem Mines in Cipocereus minensis (Wender.) Ritter (Cactaceae), an Endemic Species to Eastern Brazil

Plant mines are structures with the form of a cavity caused by consumption of host plant tissue by the insect's miner larvae. Plant mines are more common in leaves, but in Cipocereus minensis, a species in which the leaves are modified spines, the miner activity is restricted to the stem. The aim of this paper was to document the morphological and anatomical differences in the infected and uninfected stems of C. minensis due to the feeding habit of the mining agent. Fresh tissue samples of non-mined and mined young stem of C minensis were collected and examined in transverse sections. We hypothesize that the infection begins following mating when the females scratch the surface of the stem or while they feed on fruits and lay eggs, which subsequently develop into larvae, invading the cactus stem. The insect's miner larvae had mostly consumed the parenchyma tissue towards the center of the stem, and periderm formed along the entire path of the insect. This meristematic tissue or "wound periderm" is a common response for compartmentalization to isolate the damaged tissue, in this case the incubating chamber, in which the eggs will be placed. There were no signs of consumption of vascular tissue in the infested samples, further suggesting a compartmentalized infestation. The nest chamber was found in the stem pith region, with periderm surrounding an insect's miner pupa inside identified as a member of the Cerambycidae. The mining insect depends on a host plant to complete the life cycle; however, the nature of this partnership and the long-term effects of the insect on the plant tissue are unknown. The complex mechanisms by which herbivorous insects control the morphogenesis of the plant host are discussed. We propose that C. minensis has a recognition system to identify insect attack and evaluate the effectiveness of early response triggering compartmentalized defense mechanisms by protecting the injured area with a new layer of periderm.

Effects of the administration of pentoxifylline and prednisolone on the evolution of portal fibrogenesis secondary to biliary obstruction in growing animals: immunohistochemical analysis of the expression of TGF-BETA; and VEGF

OBJECTIVE: During the neonatal and infancy periods, some chronic liver diseases may lead to progressive hepatic fibrosis, which is a condition that can ultimately result in the loss of organ function and severe portal hypertension necessitating hepatic transplantation. In a previous report, pharmacological interventions were demonstrated to modulate hepatic fibrosis induced by bile duct ligation in young rats. The administration of pentoxifylline or prednisolone, or the combination of both, resulted in reduced fibrogenesis in portal spaces. The objectives of the present study were to evaluate the expression of transforming growth factor beta and vascular endothelial growth factor after bile duct ligation in young rats and to assess the effect of those same drugs on cytokine expression. METHODS: In this experimental study, 80 young rats (21 or 22 days old) were submitted either to laparotomy and common bile duct ligation or to sham surgery. The animals were allocated into four groups according to surgical procedure, and the following treatments were administered: (1) common bile duct ligation + distilled water, (2) sham surgery + distilled water, (3) common bile duct ligation + pentoxifylline, or (4) common bile duct ligation + prednisolone. After 30 days, a hepatic fragment was collected from each animal for immunohistochemical analysis using monoclonal antibodies against transforming growth factor beta and vascular endothelial growth factor. Digital morphometric and statistical analyses were performed. RESULTS: The administration of pentoxifylline reduced the transforming growth factor beta-marked area and the amount of transforming growth factor beta expressed in liver tissue. This effect was not observed after the administration of prednisolone. There was a significant reduction in vascular endothelial growth factor expression after the administration of either drug compared with the non-treatment group. CONCLUSIONS: The administration of pentoxifylline to cholestatic young rats resulted in the diminished expression of transforming growth factor beta and vascular endothelial growth factor in liver tissue. The administration of steroids resulted in the diminished expression of vascular endothelial growth factor only. These pathways may be involved in hepatic fibrogenesis in young rats submitted to bile duct ligation and exposed to pentoxifylline or prednisolone.

A Novel Method of Evaluating Ureteropelvic Junction Obstruction: Dynamic Near Infrared Fluorescence Imaging Compared to Standard Modalities to Assess Urinary Obstruction in a Swine Model

Purpose: Dynamic near infrared fluorescence imaging of the urinary tract provides a promising way to diagnose ureteropelvic junction obstruction. Initial studies demonstrated the ability to visualize urine flow and peristalsis in great detail. We analyzed the efficacy of near infrared imaging in evaluating ureteropelvic junction obstruction, renal involvement and the anatomical detail provided compared to conventional imaging modalities. Materials and Methods: Ten swine underwent partial or complete unilateral ureteral obstruction. Groups were survived for the short or the long term. Imaging was performed with mercaptoacetyltriglycine diuretic renogram, magnetic resonance urogram, excretory urogram, ultrasound and near infrared imaging. Scoring systems for ureteropelvic junction obstruction were developed for magnetic resonance urogram and near infrared imaging. Physicians and medical students graded ureteropelvic junction obstruction based on magnetic resonance urogram and near infrared imaging results. Results: Markers of vascular and urinary dynamics were quantitatively consistent among control renal units. The same markers were abnormal in obstructed renal units with significantly different times of renal phase peak, start of pelvic phase and start of renal uptake. Such parameters were consistent with those obtained with mercaptoacetyltriglycine diuretic renography. Near infrared imaging provided live imaging of urinary flow, which was helpful in identifying the area of obstruction for surgical planning. Physicians and medical students categorized the degree of obstruction appropriately for fluorescence imaging and magnetic resonance urogram. Conclusions: Near infrared imaging offers a feasible way to obtain live, dynamic images of urine flow and ureteral peristalsis. Qualitative and quantitative parameters were comparable to those of conventional imaging. Findings support fluorescence imaging as an accurate, easy to use method of diagnosing ureteropelvic junction obstruction.

Effect of cilostazol and pentoxifylline on gait biomechanics in rats with ischemic left hindlimb

Objective: The purpose of this study was to determine the impact of pharmacologic treatment with cilostazol and pentoxifylline on gait biomechanics of ischemic rat hindlimbs compared with nonischemic controls. Methods: An experimental study was designed using 30 Wistar rats divided into five groups (n = 6): control (C); ischemia (I) - animals submitted to left common iliac artery interruption without pharmacologic treatment; pentoxifylline (Pen) - rats submitted to procedure and treated with pentoxifylline 3 mg/kg twice a day for 6 weeks; cilostazol (Cil) - animals submitted to procedure and treated with cilostazol 30 mg/kg twice a day for 6 weeks; and sham (S) - animals submitted to procedure without artery interruption. Gait analysis was performed using a computed treadmill. Time, number, and duration of each hindlimb contact were obtained. The total number of contacts (TNC) and the total duration of contacts (TDC) were compared between left and right hindlimb and among groups. Left hindlimb ischemic incapacitation index (LHII) was defined by the formula: LHII = (1 - TNCleft x TDCleft/TNCright x TDCright) x 100 Results: Left hindlimb TNC values were twofold lower in I, Pen, and Cil groups than in C and S groups (P < .01). In I, Pen, and Cil groups, TNC values for the left hindlimb were half of the right hindlimb ones (P < .01). Left hindlimb TDC values were lower in I and Pen groups than the other groups (P < .01). Cil group presented twofold increased values, not different from C and S groups (P = 0.16). Right hindlimb TNC values were greater for I group (P < .01). LHII was around zero in C and S groups and 82 in both I and Pen groups (P < .01). Cil group presented a LHII of 42; higher than C and S groups, but lower than I and Pen groups (P < .01). Conclusions: Cilostazol at a dose of 30 mg/kg twice a day promoted improvement in gait performance in rats submitted to chronic hindlimb ischemia. Pentoxifylline at a dose of 3 mg/kg twice a day did not show this effect. (J Vasc Surg 2012;56:476-81.)