A double-blind comparison of the effect of the antipsychotics haloperidol and olanzapine on sleep in mania

The effects of haloperidol and olanzapine on polysomnographic measures made in bipolar patients during manic episodes were compared. Twelve DSM-IV mania patients were randomly assigned to receive either haloperidol (mean ± SD final dosage: 5.8 ± 3.8 mg) or olanzapine (mean ± SD final dosage: 13.6 ± 6.9 mg) in a 6-week, double-blind, randomized, controlled clinical trial. One-night polysomnographic evaluation was performed before and after the haloperidol or olanzapine treatment. Psychopathology and illness severity were rated respectively with the Young Mania Rating Scale (YMRS) and the Clinical Global Impressions - Bipolar version (CGI-BP). There was a significant improvement in the YMRS and CGI-BP scores at the end of the study for both groups. Mixed ANOVA used to compare the polysomnographic measures of both drugs demonstrated significant improvement in sleep measures with olanzapine. In the olanzapine group, statistically significant time-drug interaction effects on sleep continuity measures were observed: sleep efficiency (mean ± SEM pre-treatment value: 6.7 ± 20.3%; after-treatment: 85.7 ± 10.9%), total wake time (pre-treatment: 140.0 ± 92.5 min; after-treatment: 55.2 ± 44.2 min), and wake time after sleep onset (pre-treatment: 109.7 ± 70.8 min; after-treatment: 32.2 ± 20.7 min). Conversely, improvement of polysomnographic measures was not observed for the haloperidol group (P > 0.05). These results suggest that olanzapine is more effective than haloperidol in terms of sleep-promoting effects, although olanzapine is comparatively as effective as haloperidol in treating mania. Polysomnography records should provide useful information on how manic states can be affected by psychopharmacological agents.

Water deprivation and the double- depletion hypothesis: common neural mechanisms underlie thirst and salt appetite

Water deprivation-induced thirst is explained by the double-depletion hypothesis, which predicts that dehydration of the two major body fluid compartments, the extracellular and intracellular compartments, activates signals that combine centrally to induce water intake. However, sodium appetite is also elicited by water deprivation. In this brief review, we stress the importance of the water-depletion and partial extracellular fluid-repletion protocol which permits the distinction between sodium appetite and thirst. Consistent enhancement or a de novo production of sodium intake induced by deactivation of inhibitory nuclei (e.g., lateral parabrachial nucleus) or hormones (oxytocin, atrial natriuretic peptide), in water-deprived, extracellular-dehydrated or, contrary to tradition, intracellular-dehydrated rats, suggests that sodium appetite and thirst share more mechanisms than previously thought. Water deprivation has physiological and health effects in humans that might be related to the salt craving shown by our species.

Antibodies to citrullinated peptides are not associated with the rate of joint destruction in patients with a well-established diagnosis of rheumatoid arthritis

Antibodies to citrullinated peptides are highly specific for rheumatoid arthritis (RA) and represent a significant risk factor for undifferentiated polyarthritis. This prognostic ability may be related to the very diagnostic performance of these autoantibodies, since RA is a more erosive disease than other forms of arthritis. The present study evaluated an association of antibodies to citrullinated peptides and the rate of joint destruction in patients with a well-established diagnosis of RA. Seventy-one patients with RA were evaluated in 1994 and again in 2002 (functional class, joint count, Health Assessment Questionnaire score, hands X-ray). Autoantibodies (rheumatoid factor (RF), anti-perinuclear factor, anti-cyclic citrullinated peptide (CCP) antibodies) and Sharp's index were analyzed blindly. Delta Sharp was calculated as the difference in Sharp's index obtained in 1994 and 2002. During the follow-up the Health Assessment Questionnaire score increased from 0.91 ± 0.74 to 1.39 ± 0.72 (P < 0.001). Similarly, the number of swollen joints increased from 4.6 ± 5.71 to 6.4 ± 4.1 (P = 0.002). The frequency of autoantibodies and anti-CCP titer remained stable; however, serum RF concentration increased from 202.8 ± 357.6 to 416.6 ± 636.5 IU/mL (P = 0.003). Sharp's index increased from 56.7 ± 62.1 to 92.4 ± 80.9 (P < 0.001). No correlation was observed between Delta Sharp and the presence of RF, anti-perinuclear factor, and anti-CCP antibodies at baseline. Antibodies to citrullinated epitopes are specific and early markers for the diagnosis of RA but do not seem to be associated with the rate of joint destruction in patients with a well-established diagnosis of RA.

The effect of a low dose of clenbuterol on rat soleus muscle submitted to joint immobilization

The aim of the present study was to evaluate the effect of joint immobilization on morphometric parameters and glycogen content of soleus muscle treated with clenbuterol. Male Wistar (3-4 months old) rats were divided into 4 groups (N = 6 for each group): control, clenbuterol, immobilized, and immobilized treated with clenbuterol. Immobilization was performed with acrylic resin orthoses and 10 µg/kg body weight clenbuterol was administered subcutaneously for 7 days. The following parameters were measured the next day on soleus muscle: weight, glycogen content, cross-sectional area, and connective tissue content. The clenbuterol group showed an increase in glycogen (81.6%, 0.38 ± 0.09 vs 0.69 ± 0.06 mg/100 g; P < 0.05) without alteration in weight, cross-sectional area or connective tissue compared with the control group. The immobilized group showed a reduction in muscle weight (34.2%, 123.5 ± 5.3 vs 81.3 ± 4.6 mg; P < 0.05), glycogen content (31.6%, 0.38 ± 0.09 vs 0.26 ± 0.05 mg/100 mg; P < 0.05) and cross-sectional area (44.1%, 2574.9 ± 560.2 vs 1438.1 ± 352.2 µm²; P < 0.05) and an increase in connective tissue (216.5%, 8.82 ± 3.55 vs 27.92 ± 5.36%; P < 0.05). However, the immobilized + clenbuterol group showed an increase in weight (15.9%; 81.3 ± 4.6 vs 94.2 ± 4.3 mg; P < 0.05), glycogen content (92.3%, 0.26 ± 0.05 vs 0.50 ± 0.17 mg/100 mg; P < 0.05), and cross-sectional area (19.9%, 1438.1 ± 352.2 vs 1724.8 ± 365.5 µm²; P < 0.05) and a reduction in connective tissue (52.2%, 27.92 ± 5.36 vs 13.34 ± 6.86%; P < 0.05). Statistical analysis was performed using Kolmogorov-Smirnov and homoscedasticity tests. For the muscle weight and muscle glycogen content, two-way ANOVA and the Tukey test were used. For the cross-sectional area and connective tissue content, Kruskal-Wallis and Tukey tests were used. This study emphasizes the importance of anabolic pharmacological protection during immobilization to minimize skeletal muscle alterations resulting from disuse.

A bovine herpesvirus 5 recombinant defective in the thymidine kinase (TK) gene and a double mutant lacking TK and the glycoprotein E gene are fully attenuated for rabbits

Bovine herpesvirus 5 (BoHV-5), the agent of herpetic meningoencephalitis in cattle, is an important pathogen of cattle in South America and several efforts have been made to produce safer and more effective vaccines. In the present study, we investigated in rabbits the virulence of three recombinant viruses constructed from a neurovirulent Brazilian BoHV-5 strain (SV507/99). The recombinants are defective in glycoprotein E (BoHV-5gEΔ), thymidine kinase (BoHV-5TKΔ) and both proteins (BoHV-5gEΔTKΔ). Rabbits inoculated with the parental virus (N = 8) developed neurological disease and died or were euthanized in extremis between days 7 and 13 post-infection (pi). Infectivity was detected in several areas of their brains. Three of 8 rabbits inoculated with the recombinant BoHV-5gEΔ developed neurological signs between days 10 and 15 pi and were also euthanized. A more restricted virus distribution was detected in the brain of these animals. Rabbits inoculated with the recombinants BoHV-5TKΔ (N = 8) or BoHV-5gEΔTKΔ (N = 8) remained healthy throughout the experiment in spite of variable levels of virus replication in the nose. Dexamethasone (Dx) administration to rabbits inoculated with the three recombinants at day 42 pi did not result in viral reactivation, as demonstrated by absence of virus shedding and/or increase in virus neutralizing titers. Nevertheless, viral DNA was detected in the trigeminal ganglia or olfactory bulbs of all animals at day 28 post-Dx, demonstrating they were latently infected. These results show that recombinants BoHV-5TKΔ and BoHV-5gEΔTKΔ are attenuated for rabbits and constitute potential vaccine candidates upon the confirmation of this phenotype in cattle.

Effects of isoflavone on the learning and memory of women in menopause: a double-blind placebo-controlled study

Hormone decline is common to all women during aging and, associated with other factors, leads to cognitive impairment. Its replacement enhances cognitive performance, but not all women present a clinical and family or personal history that justifies its use, mainly women with a history of cancer. The aim of this study was to determine whether a daily oral dose of 80 mg of isoflavone extract for 4 months can produce benefits in women with low hormone levels, contributing to improvement in cognitive aspects. The sample comprised 50- to 65-year-old women whose menstruation had ceased at least 1 year before and who had not undergone hormone replacement. The volunteers were allocated to two groups of 19 individuals each, i.e., isoflavone and placebo. There was a weak correlation between menopause duration and low performance in the capacity to manipulate information (central executive). We observed an increase in the capacity to integrate information in the group treated with isoflavone, but no improvement in the capacity to form new memories. We did not observe differences between groups in terms of signs and symptoms suggestive of depression according to the Geriatric Depression Scale. Our results point to a possible beneficial effect of isoflavone on some abilities of the central executive. These effects could also contribute to minimizing the impact of memory impairment. Further research based on controlled clinical trials is necessary to reach consistent conclusions.

Expression of MMP-2 and MMP-9 in the rat trigeminal ganglion during the development of temporomandibular joint inflammation

Orofacial pain is a prevalent symptom in modern society. Some musculoskeletal orofacial pain is caused by temporomandibular disorders (TMDs). This condition has a multi-factorial etiology, including emotional factors and alteration of the masticator muscle and temporomandibular joints (TMJs). TMJ inflammation is considered to be a cause of pain in patients with TMD. Extracellular proteolytic enzymes, specifically the matrix metalloproteinases (MMPs), have been shown to modulate inflammation and pain. The purpose of this investigation was to determine whether the expression and level of gelatinolytic activity of MMP-2 and MMP-9 in the trigeminal ganglion are altered during different stages of temporomandibular inflammation, as determined by gelatin zymography. This study also evaluated whether mechanical allodynia and orofacial hyperalgesia, induced by the injection of complete Freund's adjuvant into the TMJ capsule, were altered by an MMP inhibitor (doxycycline, DOX). TMJ inflammation was measured by plasma extravasation in the periarticular tissue (Evans blue test) and infiltration of polymorphonuclear neutrophils into the synovial fluid (myeloperoxidase enzyme quantification). MMP expression in the trigeminal ganglion was shown to vary during the phases of the inflammatory process. MMP-9 regulated the early phase and MMP-2 participated in the late phase of this process. Furthermore, increases in plasma extravasation in periarticular tissue and myeloperoxidase activity in the joint tissue, which occurred throughout the inflammation process, were diminished by treatment with DOX, a nonspecific MMP inhibitor. Additionally, the increases of mechanical allodynia and orofacial hyperalgesia were attenuated by the same treatment.

Effects of immobilization and remobilization on the ankle joint in Wistar rats

A sprained ankle is a common musculoskeletal sports injury and it is often treated by immobilization of the joint. Despite the beneficial effects of this therapeutic measure, the high prevalence of residual symptoms affects the quality of life, and remobilization of the joint can reverse this situation. The aim of this study was to analyze the effects of immobilization and remobilization on the ankle joint of Wistar rats. Eighteen male rats had their right hindlimb immobilized for 15 days, and were divided into the following groups: G1, immobilized; G2, remobilized freely for 14 days; and G3, remobilized by swimming and jumping in water for 14 days, performed on alternate days, with progression of time and a series of exercises. The contralateral limb was the control. After the experimental period, the ankle joints were processed for microscopic analysis. Histomorphometry did not show any significant differences between the control and immobilized/remobilized groups and members, in terms of number of chondrocytes and thickness of the articular cartilage of the tibia and talus. Morphological analysis of animals from G1 showed significant degenerative lesions in the talus, such as exposure of the subchondral bone, flocculation, and cracks between the anterior and mid-regions of the articular cartilage and the synovial membrane. Remobilization by therapeutic exercise in water led to recovery in the articular cartilage and synovial membrane of the ankle joint when compared with free remobilization, and it was shown to be an effective therapeutic measure in the recovery of the ankle joint.

Effects of conventional vs high-dose rocuronium on the QTc interval during anesthesia induction and intubation in patients undergoing coronary artery surgery: a randomized, double-blind, parallel trial

Myocardial ischemia, as well as the induction agents used in anesthesia, may cause corrected QT interval (QTc) prolongation. The objective of this randomized, double-blind trial was to determine the effects of high- vs conventional-dose bolus rocuronium on QTc duration and the incidence of dysrhythmias following anesthesia induction and intubation. Fifty patients about to undergo coronary artery surgery were randomly allocated to receive conventional-dose (0.6 mg/kg, group C, n=25) or high-dose (1.2 mg/kg, group H, n=25) rocuronium after induction with etomidate and fentanyl. QTc, heart rate, and mean arterial pressure were recorded before induction (T0), after induction (T1), after rocuronium (just before laryngoscopy; T2), 2 min after intubation (T3), and 5 min after intubation (T4). The occurrence of dysrhythmias was recorded. In both groups, QTc was significantly longer at T3 than at baseline [475 vs 429 ms in group C (P=0.001), and 459 vs 434 ms in group H (P=0.005)]. The incidence of dysrhythmias in group C (28%) and in group H (24%) was similar. The QTc after high-dose rocuronium was not significantly longer than after conventional-dose rocuronium in patients about to undergo coronary artery surgery who were induced with etomidate and fentanyl. In both groups, compared with baseline, QTc was most prolonged at 2 min after intubation, suggesting that QTc prolongation may be due to the nociceptive stimulus of intubation.

Chemical profile of sugarcane spirits produced by double distillation methodologies in rectifying still

The objective of this study was to determine the chemical profile of sugarcane spirits produced by different double distillation methodologies in rectifying still. Fermented sugarcane juice was distilled in rectifying still according to three double distillation methodologies: the methodology used for cognac production; the methodology used for whisky production; and the 10-80-10 percentage composition methodology, referring to the volumes of head, heart and tail of the distillate fractions from the second distillation. For comparison purposes, a simple distilled spirit was also produced. The distillates were analyzed for concentrations of ethanol, copper, volatile acidity, furfural and hydroxymethylfurfural, aldehydes, esters, methanol and higher alcohols. The spirits were also evaluated on the sensory attributes of aroma, taste and preference. Compared to simple distillation, double distillation improved the chemical quality of the spirits, since it has reduced the concentrations of acids, aldehydes, esters, methanol, higher alcohols and, consequently, their coefficient of congeners. Regardless of the methodology employed, the double distillation improved the sensory quality of the spirits since they obtained higher sensory acceptance in relation to spirits produced by simple distillation. Among double distilled spirits, the one produced according to whisky methodology obtained the best scores from appraisers on the aroma and flavor parameters and it was also the most preferred.

Effects of grape powder supplementation on inflammatory and antioxidant markers in hemodialysis patients: A randomized double-blind study

Introduction: Polyphenols contained in natural sources such as grapes, have been considered pharmacological agents to combat oxidative stress and inflammation, common features in Chronic Kidney Disease patients. Objective: To evaluate the effects of grape powder supplementation on inflammatory and antioxidant biomarkers in hemodialysis (HD) patients. Methods: The double-blind placebo-controlled randomized clinical trial evaluated non-diabetic HD patients that received grape powder (500 mg of polyphenols/day) (n = 16, 9 men, 53.0 ± 9.8 years of age, 111.6 ± 58.2 HD months) or placebo (n = 16, 9 men, 52.7 ± 13.7 years of age, 110.4 ± 93.1 HD months) for five weeks. The glutathione peroxidase (GSH-Px) activity and C-reactive protein (CRP) levels were evaluated by ELISA method. Results: After the intervention period, the patients receiving grape powder showed an increase in the GSH-Px activity (16.5 (41.0) to 42.0 (43.3) nmol/min/ml) (p < 0.05) and they did not have the CRP levels increased as seen in placebo group (2.6 (0.28) to 2.8 (0.23 mg/L) (p < 0.05). Conclusion: The use of grape powder as phenolic source could play an important role as an antioxidant and anti-inflammatory agent in non-diabetic HD patients.