Angiotensin-converting enzyme inhibition augments the expression of rat elastase-2, an angiotensin II-forming enzyme

Becari C, Teixeira FR, Oliveira EB, Salgado MC. Angiotensin-converting enzyme inhibition augments the expression of rat elastase- 2, an angiotensin II-forming enzyme. Am J Physiol Heart Circ Physiol 301: H565-H570, 2011. First published May 20, 2011; doi:10.1152/ajpheart.00534.2010.-Mounting evidence suggest that tissue levels of angiotensin (ANG) II are maintained in animals submitted to chronic angiotensin-converting enzyme (ACE) inhibitor treatment. We examined the expression levels of transcripts for elastase-2, a chymostatin-sensitive serine protease identified as the alternative pathway for ANG II generation from ANG I in the rat vascular tissue and the relative role of ACE-dependent and -independent pathways in generating ANG II in the rat isolated carotid artery rings of spontaneously hypertensive rats (SHR) and Wistar normotensive rats (WNR) treated with enalapril for 7 days. Enalapril treatment decreased blood pressure of SHR only and resulted in significantly more elastase-2 mRNA expression in carotid artery of both enalapril-treated WNR and SHR. Captopril induced a comparable rightward shift of concentration-response curves to ANG I in vehicle and enalapril-treated rats, although this effect was of lesser magnitude in SHR group. Chymostatin induced a rightward shift of the dose response to ANG I in vehicle-treated and a decrease in maximal effect of 22% in enalapril-treated WNR group. Maximal response induced by ANG I was remarkably reduced by chymostatin in enalapril-treated SHR carotid artery (by 80%) compared with controls (by 23%). Our data show that chronic ACE inhibition was associated with augmented functional role of non-ACE pathway in generating ANG II and increased elastase-2 gene expression, suggesting that this protease may contribute as an alternative pathway for ANG II generation when ACE is inhibited in the rat vascular tissue.

Endocrine signatures underlying plasticity in postembryonic development of a lower termite, Cryptotermes secundus (Kalotermitidae)

Wood-dwelling termites are characterized by an extremely high and unique developmental flexibility that allows workers, which are immatures, to explore all caste options. The endocrine signatures underlying this flexibility are only vaguely understood. We determined juvenile hormone (JH) and ecdysteroid hemolymph titers during postembryonic development and in terminal instars of the drywood termite Cryptotermes secundus using field and laboratory colonies. Postembryonic development is characterized by a drop in JH titers at the transition from larval (individuals without wing buds) to nymphal (individuals with wing buds) instars. JH titers were low in winged sexuals and reproducing primary reproductives (< 200 pg/mu l) but were by an order of magnitude higher in neotenic replacement reproductives. The unique regressive molts of termites seem to be characterized by elevated JH titers, compared with progressive or stationary molts. Ecdysteroid titers were generally low in nymphal instars and in primary reproductives (< 50 pg/mu l). It was only during the third and fourth nymphal instars and in winged sexuals where some individuals showed elevated ecdysteroid titers. These results are the most comprehensive endocrinological data set available for any lower termite, with the potential to serve as baseline for understanding the extreme developmental flexibility underlying the evolution of social life in termites.

Role of mixed Th1 and Th2 serum cytokines on pathogenesis and prognosis of hantavirus pulmonary syndrome

The hantavirus pulmonary syndrome (HPS) is an emerging syndrome in the Americas. The disease results from intense immune activation and changes in vascular permeability. The aim of this study was to determine the profile of serum cytokines in HPS patients looking for correlation with the clinical parameters, severity and outcome of illness. Studying 21 HPS patients, we found that IL-6 may have an important role in the pathogenesis of HPS, being associated with fatal outcome. Our results also support a mixed Th1/Th2 immune response during the course of HPS and that the magnitude of Th1 response effector cytokines is correlated to HPS severity. The decreased levels of TGF-beta observed in HPS patients suggest that immunoregulatory activity could be damaged in these patients. (c) 2008 Elsevier Masson SAS. All rights reserved.

Quality control of blood irradiation with a teletherapy unit: damage to stored red blood cells after cobalt-60 gamma irradiation

BACKGROUND: Previous publications have documented the damage caused to red blood cells (RBCs) irradiated with X-rays produced by a linear accelerator and with gamma rays derived from a Cs-137 source. The biologic effects on RBCs of gamma rays from a Co-60 source, however, have not been characterized. STUDY DESIGN AND METHODS: This study investigated the effect of 3000 and 4000 cGy on the in vitro properties of RBCs preserved with preservative solution and irradiated with a cobalt teletherapy unit. A thermal device equipped with a data acquisition system was used to maintain and monitor the blood temperature during irradiation. The device was rotated at 2 r.p.m. in the irradiation beam by means of an automated system. The spatial distribution of the absorbed dose over the irradiated volume was obtained with phantom and thermoluminescent dosimeters (TLDs). Levels of Hb, K+, and Cl- were assessed by spectrophotometric techniques over a period of 45 days. The change in the topology of the RBC membrane was investigated by flow cytometry. RESULTS: Irradiation caused significant changes in the extracellular levels of K+ and Hb and in the organizational structure of the phospholipid bilayer of the RBC membrane. Blood temperature ranged from 2 to 4 degrees C during irradiation. Rotation at 2 r.p.m. distributed the dose homogeneously (92%-104%) and did not damage the RBCs. CONCLUSIONS: The method used to store the blood bags during irradiation guaranteed that all damage caused to the cells was exclusively due to the action of radiation at the doses applied. It was demonstrated that prolonged storage of Co-60-irradiated RBCs results in loss of membrane phospholipids asymmetry, exposing phosphatidylserine (PS) on the cells` surface with a time and dose dependence, which can reduce the in vivo recovery of these cells. A time- and dose-dependence effect on the extracellular K+ and plasma-free Hb levels was also observed. The magnitude of all these effects, however, seems not to be clinically important and can support the storage of irradiated RBC units for at last 28 days.

THE EFFECT OF DIFFERENT VOLUMES OF ACUTE RESISTANCE EXERCISE ON ELDERLY INDIVIDUALS WITH TREATED HYPERTENSION

Scher, LML, Ferriolli, E, Moriguti, JC, Scher, R, and Lima, NKC. The effect of different volumes of acute resistance exercise on elderly individuals with treated hypertension. J Strength Cond Res 25(4): 1016-1023, 2011-Acute resistance exercise can reduce the blood pressure (BP) of hypertensive subjects. The aim of this study was to evaluate the effect of different volumes of acute low-intensity resistance exercise over the magnitude and the extent of BP changes in treated hypertensive elderly individuals. Sixteen participants (7 men, 9 women), with mean age of 68 6 5 years, performed 3 independent randomized sessions: Control (C: 40 minutes of rest), Exercise 1 (E1: 20 minutes, 1 lap in the circuit), and Exercise 2 (E2: 40 minutes, 2 laps in the circuit) with the intensity of 40% of 1 repetition maximum. Blood pressure was measured before (during 20 minutes) and after each session (every 5 minutes during 60 minutes) using both a mercury sphygmomanometer and a semiautomatic device (Omrom-HEM-431). After that, 24-hour ambulatory blood pressure monitoring was performed (Dyna-MAPA). Blood pressure decreased during the first 60 minutes (systolic: p < 0.01, diastolic: p < 0.05) after all exercise sessions. Only the highest volume session promoted a reduction of mean systolic 24-hour BP and awake BP (p, 0.05) after exercise, with higher diastolic BP during sleep (p, 0.05). Diastolic 24-hour BP and both systolic and diastolic BP during sleep were higher after E1 (p, 0.05). Concluding, acute resistive exercise sessions in a circuit with different volumes reduced BP during the first 60 minutes after exercise in elderly individuals with treated hypertension. However, only the highest volume promoted a reduction of mean 24-hour and awake systolic BP.

Albendazole-praziquantel interaction in healthy volunteers: kinetic disposition, metabolism and enantioselectivity

center dot Pharmacokinetic interactions between albendazole and praziquantel are based on plasma concentrations of the enantiomeric mixture of both drugs with contradictory data, although the antiparasitic activity arises from (-)-(R)-praziquantel and (+)-albendazole sulfoxide. WHAT THIS STUDY ADDS center dot The pharmacokinetic interaction between albendazole and praziquantel is enantioselective. Praziquantel increased the plasma concentrations of (+)-albendazole sulfoxide more than those of (-)-albendazole sulfoxide and the administration of albendazole did not change the kinetic disposition of (+)-(S)-praziquantel, but increased the plasma concentration of (-)-(R)-praziquantel. AIM This study investigated the kinetic disposition, metabolism and enantioselectivity of albendazole (ABZ) and praziquantel (PZQ) administered alone and in combination to healthy volunteers. METHODS A randomized crossover study was carried out in three phases (n = 9), in which some volunteers started in phase 1 (400 mg ABZ), others in phase 2 (1500 mg PZQ), and the remaining volunteers in phase 3 (400 mg ABZ + 1500 mg PZQ). Serial blood samples were collected from 0-48 h after drug administration. Pharmacokinetic parameters were calculated using a monocompartmental model with lag time and were analyzed using the Wilcoxon test; P < 0.05. RESULTS The administration of PZQ increased the plasma concentrations of (+)-ASOX (albendazole sulphoxide) by 264% (AUC 0.99 vs. 2.59 mu g ml-1 h), (-)-ASOX by 358% (0.14 vs. 0.50 mu g ml-1 h) and albendazole sulfone (ASON) by 187% (0.17 vs. 0.32 mu g ml-1 h). The administration of ABZ did not change the kinetic disposition of (+)-(S)-PZQ (-)-(R)-4-OHPZQ or (+)-(S)-4-OHPZQ, but increased the plasma concentration of (-)-(R)-PZQ by 64.77% (AUC 0.52 vs. 0.86 mu g ml-1 h). CONCLUSIONS The pharmacokinetic interaction between ABZ and PZQ in healthy volunteers was demonstrated by the observation of increased plasma concentrations of ASON, both ASOX enantiomers and (-)-(R)-PZQ. Clinically, the combination of ABZ and PZQ may improve the therapeutic efficacy as a consequence of higher concentration of both active drugs. On the other hand, the magnitude of this elevation may represent an increased risk of side effects, requiring, certainly, reduction of the dosage. However, further studies are necessary to evaluate the efficacy and safety of this combination.

Food energy content influences food portion size estimation by nutrition students

Background: Food portion size estimation involves a complex mental process that may influence food consumption evaluation. Knowing the variables that influence this process can improve the accuracy of dietary assessment. The present study aimed to evaluate the ability of nutrition students to estimate food portions in usual meals and relate food energy content with errors in food portion size estimation. Methods: Seventy-eight nutrition students, who had already studied food energy content, participated in this cross-sectional study on the estimation of food portions, organised into four meals. The participants estimated the quantity of each food, in grams or millilitres, with the food in view. Estimation errors were quantified, and their magnitude were evaluated. Estimated quantities (EQ) lower than 90% and higher than 110% of the weighed quantity (WQ) were considered to represent underestimation and overestimation, respectively. Correlation between food energy content and error on estimation was analysed by the Spearman correlation, and comparison between the mean EQ and WQ was accomplished by means of the Wilcoxon signed rank test (P < 0.05). Results: A low percentage of estimates (18.5%) were considered accurate (+/- 10% of the actual weight). The most frequently underestimated food items were cauliflower, lettuce, apple and papaya; the most often overestimated items were milk, margarine and sugar. A significant positive correlation between food energy density and estimation was found (r = 0.8166; P = 0.0002). Conclusions: The results obtained in the present study revealed a low percentage of acceptable estimations of food portion size by nutrition students, with trends toward overestimation of high-energy food items and underestimation of low-energy items.

Cardiovascular responses to microinjection of noradrenaline into the medial amygdaloid nucleus of conscious rats result from alpha(2)-receptor activation and vasopressin release

The medial amygdaloid nucleus (MeA) is involved in the modulation of physiological and behavioral processes, as well as regulation of the autonomic nervous system. Moreover, MeA electrical stimulation evokes cardiovascular responses. Thus, as noradrenergic receptors are present in this structure, the present study tested the effects of local noradrenaline (NA) microinjection into the MeA on cardiovascular responses in conscious rats. Moreover, we describe the types of adrenoceptor involved and the peripheral mechanisms involved in the cardiovascular responses. Increasing doses of NA (3, 9, 27 or 45 nmol/100 nL) microinjected into the MeA of conscious rats caused dose-related pressor and bradycardic responses. The NA cardiovascular effects were abolished by local pretreatment of the MeA with 10 nmol/100 nL of the specific alpha(2)-receptor antagonist RX821002, but were not affected by local pretreatment with 10 nmol/100 nL of the specific alpha(1)-receptor antagonist WB4101. The magnitude of pressor response evoked by NA microinjected into the MeA was potentiated by intravenous pretreatment with the ganglion blocker pentolinium (5 mg/kg), and blocked by intravenous pretreatment with the selective V(1)-vasopressin antagonist dTyr(CH(2))(5)(Me)AVP (50 mu g/kg). In conclusion, our results show that microinjection of NA into the MeA of conscious rats activates local alpha(2)-adrenoceptors, evoking pressor and bradycardic responses, which are mediated by vasopressin release.

Effect of acute restraint stress on the tachycardiac and bradycardiac responses of the baroreflex in rats

In the present study, we evaluated cardiac baroreflex responses of rats submitted to acute restraint stress. The baroreflex was tested: immediately before, during a 30 min exposure to restraint stress, as well as 30 and 60 min after ending the stress session (recovery period). Restraint increased both mean arterial pressure (MAP) and heart rate (HR). The magnitude of tachycardiac responses evoked by intravenous infusion of sodium nitroprusside was higher during restraint stress, whereas that of bradycardiac responses evoked by intravenous infusion of phenylephrine was decreased. Restraint-evoked baroreflex changes were still observed at 30 min into the recovery period, although MAP and HR values had already returned to control values. The baroreflex was back to control values at 60 min of the recovery period. Intravenous administration of the selective beta(1)-adrenoceptor antagonist atenolol blocked the restraint-evoked increase in the tachycardiac baroreflex response, but did not affect the effects on the bradycardiac response. In conclusion, the present results suggest that psychological stresses, such as those resulting from acute restraint, affect the baroreflex. Restraint facilitated the tachycardiac baroreflex response and reduced the bradycardiac response. Restraint-related effects on baroreflex persisted for at least 30 min after ending restraint, although MAP and HR had already returned to control levels. The cardiac baroreflex returned to control values 60 min after the end of restraint, indicating non-persistent effects of acute restraint on the baroreflex. Results also indicate that the influence of restraint stress on the baroreflex tachycardiac response is mainly dependent on cardiac sympathetic activity, whereas the action on the bradycardiac response is mediated by the cardiac parasympathetic component.

Conspecific and heterospecific alarm substance induces behavioral responses in piau fish Leporinus piau

In ostariophysan fish, the detection of alarm substance released from the skin of a conspecific or a sympatric heterospecific may elicit alarm reactions or antipredator behavioral responses. In this study, experiments were performed to characterize and quantify the behavioral response threshold of Leporinus piau, both individually and in schools, to growing dilutions of conspecific (CAS) and heterospecific skin extract (HAS). The predominant behavioral response to CAS stock stimulation was biphasic for fish held individually, with a brief initial period of rapid swimming followed by a longer period of immobility or reduced swimming activity. As the dilution of skin extract was increased, the occurrence and magnitude of the biphasic alarm response tended to decrease, replaced by a slowing of locomotion. Slowing was the most common antipredator behavior, observed in 62.5% of animals submitted to HAS stimulation. School cohesion, measured as proximity of fish to the center of the school, and swimming activity near the water surface significantly increased after exposure to CAS when compared with the control group exposed to distilled water. Histological analysis of the epidermis revealed the presence of Ostariophysi-like club cells. The presence of these cells and the behavioral responses to conspecific and heterospecific skin extract stimulation suggest the existence of a pheromone alarm system in L. piau similar to that in Ostariophysi, lending further support for the neural processing of chemosensory information in tropical freshwater fish.

Headache and Symptoms of Temporomandibular Disorder: An Epidemiological Study

Objectives.-A population-based cross-sectional study was conducted to estimate the prevalence of migraine, episodic tension-type headaches (ETTH), and chronic daily headaches (CDH), as well as the presence of symptoms of temporomandibular disorders (TMD) in the adult population. Background.-The potential comorbidity of headache syndromes and TMD has been established mostly based on clinic-based studies. Methods.-A representative sample of 1230 inhabitants (51.5% women) was interviewed by a validated phone survey. TMD symptoms were assessed through 5 questions, as recommended by the American Academy of Orofacial Pain, in an attempt to classify possible TMD. Primary headaches were diagnosed based on the International Classification of Headache Disorders. Results.-When at least 1 TMD symptom was reported, any headache happened in 56.5% vs 31.9% (P < .0001) in those with no symptoms. For 2 symptoms, figures were 65.1% vs 36.3% (P < .0001); for 3 or more symptoms, the difference was even more pronounced: 72.8% vs 37.9%. (P < .0001). Taking individuals without headache as the reference, the prevalence of at least 1 TMD symptom was increased in ETTH (prevalence ratio = 1.48, 95% confidence interval = 1.20-1.79), migraine (2.10, 1.80-2.47) and CDH (2.41, 1.84-3.17). At least 2 TMD symptoms also happened more frequently in migraine (4.4, 3.0-6.3), CDH (3.4; 1.5-7.6), and ETTH (2.1; 1.3-3.2), relative to individuals with no headaches. Finally, 3 or more TMD symptoms were also more common in migraine (6.2; 3.8-10.2) than in no headaches. Differences were significant for ETTH (2.7 1.5-4.8), and were numerically but not significant for CDH (2.3; 0.66-8.04). Conclusions.-Temporomandibular disorder symptoms are more common in migraine, ETTH, and CDH relative to individuals without headache. Magnitude of association is higher for migraine. Future studies should clarify the nature of the relationship.

Intravitreal Bevacizumab for Diabetic Macular Edema Associated With Severe Capillary Loss: One-Year Results of a Pilot Study

PURPOSE: To evaluate the effects of intravitreal bevacizumab in patients with diabetic macular edema (DME) associated with severe capillary loss. DESIGN: Multicenter, open-label, nonrandomized study. METHODS: SETTING: Two tertiary ophthalmic referral centers in Brazil. STUDY POPULATION: Ten consecutive patients with DME and ""severe"" capillary loss. OBSERVATION PROCEDURES: Intravitreal injection(s) of bevacizumab (1.5 mg). Standardized ophthalmic evaluation was performed at baseline and at weeks 8, 16, 24, and 54. MAIN OUTCOME MEASURES: Changes in best-corrected visual acuity (BCVA) and in optical coherence tomography variables (central macular thickness [CMT] and total macular volume [TMV]). RESULTS: Significant changes in BCVA and in CMT/TMV were noted throughout the study (P<.001, P=.009, and P<.001, respectively). The mean logarithm of the minimal angle of resolution Early Treatment Diabetic Retinopathy Study BCVA was 0.786 (similar to 20/125(+1)) at baseline, 0.646 (similar to 20/80(-2)) at week 8, 0.580 (20/80(+1)) at week 16, 0.574 (similar to 20/80(+1)) at week 24, and 0.558 (similar to 20/80(+2)) at week 54. Compared with baseline, a significant change in BCVA was noted at all follow-up visits (P <=.008). The mean CMT/TMV values were, respectively, 472.6/10.9 at baseline, 371.4/9.9 at week 8, 359.5/9.8 at week 16, 323.9/9-4 at week 24, and 274.6/8.7 at week 54. Compared with baseline, a significant change in both CMT and TMV was noted only at 24 and 54 weeks (P <=.007). At 54 weeks, fluorescein angiography demonstrated no change in the extent of macular capillary loss and reduced dye leakage as compared with baseline in all patients. CONCLUSIONS: Favorable changes in BCVA and in CMT/TMV observed throughout 1 year suggest that intra-vitreal bevacizumab may be a viable alternative treatment for the management of patients with DME and severe capillary loss. (Am J Ophthalmol 2009;147:1022-1030. (C) 2009 by Elsevier Inc. All rights reserved.)

Intraoperative bleeding during vitrectomy for diabetic tractional retinal detachment with versus without preoperative intravitreal bevacizumab (IBeTra study)

Aims: To compare the amount of intraoperative intraocular bleeding in patients with diabetes with macula-involving tractional retinal detachment (TRD) undergoing pars plana vitrectomy (PPV) with and without preoperative intravitreal bevacizumab (IVB) injection. Methods: An institutional study was carried out with consecutive patients with diabetic retinopathy and macula-involving TRD of recent (3 months) onset who were randomly assigned to PPV only (PPV group) or PPV combined with one IVB (1.5 mg/0.06 ml) injection 2 weeks prior to surgery (bevacizumab (BEV)/PPV group). All patients underwent 23-gauge PPV 3 weeks after baseline. The main outcome measure was erythrocyte count in the fluid retrieved from the vitrectomy cassette using a Neubauer counting chamber. Results: The study included 20 patients. The mean erythrocyte count was 14865x10(3) (SD 19332x10(3); median 4500x10(3)) cells in the BEV/PPV group, and 176240x10(3) (SD 108375x10(3); median 166600x10(3)) cells in the PPV group. The mean erythrocyte count was significantly lower in the BEV/PPV group than in the PPV group (p < 0.0001). No major adverse events were identified. Conclusion: Preoperative IVB injection was associated with reduced intraocular bleeding during 23-gauge PPV for diabetic macula-involving TRD. Further studies are needed to confirm our preliminary findings.

Intravitreal triamcinolone versus bevacizumab for treatment of refractory diabetic macular oedema (IBEME study)

Background/aims: The aim of this study was to compare the morphological and visual acuity outcomes associated with a single intravitreal injection of triamcinolone acetonide versus bevacizumab for the treatment of refractory diffuse diabetic macular oedema. Methods: Twenty-eight patients were randomly assigned to receive a single intravitreal injection of either 4 mg/0.1 ml triamcinolone acetonide or 1.5 mg/0.06 ml bevacizumab. Comprehensive ophthalmic evaluation was performed at baseline and at weeks 1, 4, 8 (+/- 1), 12 (+/- 2) and 24 (+/- 2) after treatment. Main outcome measures included central macular thickness measured with optical coherence tomography (OCT) and best corrected Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity. Results: Twenty-six patients (26 eyes) completed all study visits (two patients missed two consecutive study visits). Central macular thickness was significantly reduced in the intravitreal triamcinolone group compared with the bevacizumab group at weeks 4, 8, 12 and 24 (p<0.05). Logarithm of the minimum angle of resolution (LogMAR) best-corrected visual acuity was significantly higher at weeks 8 (0.69; similar to 20/100(+1)) and 12 (0.74; 20/100(-2)) in the intravitreal triamcinolone group compared with the bevacizumab group (weeks 8 (0.83; similar to 20/125(-1)) and 12 (0.86; 20/ 160(+2))) (p<0.05). Significant change from baseline in mean intraocular pressure (mmHg) was seen at week 4 (+2.25) only in the intravitreal triamcinolone group (p<0.0001). No patient had observed cataract progression during the study. Conclusions: One single intravitreal injection of triamcinolone may offer certain advantages over bevacizumab in the short-term management of refractory diabetic macular oedema, specifically with regard to changes in central macular thickness. The actual clinical relevance of our preliminary findings, however, remains to be determined in future larger studies.

OCT findings in macular hole formation in eyes with complete vitreofoveal separation

The current study describes the morphologic macular features in two eyes that developed full-thickness macular holes in the setting of documented vitreofoveal separation. Using third-generation optical coherence tomography, complete vitreofoveal separation associated with the disruption of the inner foveal retina was documented in both cases. Five months after presentation, decreased vision and epiretinal membrane formation associated with development of a full-thickness macular hole were observed in the first patient. In the second patient, a full-thickness macular hole was demonstrated by optical coherence tomography 6 weeks after presentation. These findings suggest that full-thickness macular holes may develop in eyes with vitreofoveal separation. Evidence of the disturbance of the inner foveal architecture on optical coherence tomography indicates the potential role of factors other than anteroposterior or oblique vitreoretinal tractional forces in the genesis of some full-thickness macular holes.