Effect of the immunosuppressants on hepatocyte proliferation and apoptosis in a young animal model of liver regeneration: An immunohistochemical study using tissue microarrays

Hepatocyte proliferation and apoptosis (programmed cell death) occur during the liver parenchyma regeneration and the liver size modeling is mainly controlled by hepatocyte apoptosis. The purpose of the present study was to verify the influence of immunosuppressant drugs on these phenomena by utilizing tissue microarray techniques. Thirty-six weaning rats (age 21-23 days, weight 30-50 g) were divided into six groups: control, sham, hepatectomy, hepatectomy plus solumedrol, hepatectomy plus CsA, and hepatectomy plus Tac. The animals were killed one day after hepatectomy, and the remnant livers were weighed and harvested for tissue microarray sections. Liver cell proliferation was evaluated by staining for PCNA and apoptosis was detected by the TUNEL method. It was verified that CsA promoted a decrease in the liver weight, Tac and CsA decreased the proliferation index of hepatocytes, and glucocorticoid had no significant effects. The apoptosis index was not altered by hepatectomy or immunosuppressants. Our data indicate that, in the growing rat, CsA and Tac have negative effects on hepatocyte proliferation and have no effect on the hepatocyte apoptosis.

Effect of Musculoskeletal Pain on Sexuality of Male Adolescents and. Adults with Juvenile Idiopathic Arthritis

Objective. To develop a questionnaire for the evaluation of sexuality of male patients with juvenile idiopathic arthritis (JIA). Methods. A cohort of male patients with rheumatoid factor (RF)-negative polyarticular. JIA according to the 2004 revised ILAR criteria and inactive disease was Studied. The Health Assessment Questionnaire (HAQ) was applied to all patients. As a control group, 120 age-matched males of the same socioeconomic status were evaluated. A self-administered Structured instrument, the Male Sexual Evaluation Questionnaire (MSEQ), was developed by multiprofessional experts to assess sexual life, including satisfaction, practice. and related functional aspects. Results. Thirty-two male patients with RF-negative polyarticular JIA [mean age 20.8 +/- 3.8 yrs (range 16-26), mean disease duration 15.4 +/- 3.6 yrs (range 13-20)] were studied. Mean HAQ score was 1.25 +/- 0.67 (range 0.1-2.1). Masturbation was practiced similarly by patients and controls (87.5% vs 91%; p > 0.999), although joint pain was observed in only 2 (7%) patients. Regular sexual intercourse (>= once/week) was reported by 78% of patients and 62% of controls (p = 0.86). Joint pain during intercourse was more frequent in patients (48% vs 3% in controls; p < 0.001). The mean HAQ score was higher in the 12 patients with,joint pain (hips = 3, knees = 5, and hips + knees = 4) during intercourse compared to the 13 patients without joint pain (1.82 +/- 0.27 vs 1.43 +/- 0.32; p < 0.05). Preserved desire and satisfaction were universal findings for all JIA patients and controls. Conclusion. The MSEQ was applicable to this cohort of male patients with RF-negative polyarticular JIA and showed that sexual life is preserved despite longterm disease, morbidity/functional dysfunction, and joint pain. (First Release May 1 2009: J Rheumatol 2009;36: 1337-42; doi: 10.3899/jrheum.080867)

Protective effect of carbon dioxide against bacterial peritonitis induced in rats

Carbon dioxide (CO(2)) has been used in the food industry as an antimicrobial agent. This study aimed to investigate whether CO(2) pneumoperitoneum might act similarly as an antimicrobial agent in the infected peritoneal cavity. Peritonitis was induced in 58 rats by intraabdominal injection of an Escherichia coli inoculum (6 x 105 colony-forming units [CFU]/ml). Control rats were injected with saline solution. The rats were randomly divided into four groups: rat control (RC, n = 15), bacterial inoculation control (BIC, n = 10), bacterial inoculation and laparotomy (BIL, n = 17), and bacterial inoculation and CO(2) pneumoperitoneum (BIP, n = 16). The survival rates and histopathologic changes in the abdominal wall muscles, spleen, liver, intestines, and omentum were evaluated, and the samples were classified as ""preserved"" or ""inflamed"" (acute inflammation or tissue regeneration). The survival rates for the four groups were as follows: RC (100%), BIP (75%), BIL (53%), and BIC (30%). With regard to survival rates, statistically significant differences were observed between the following groups: RC and BIC (p = 0.0009), RC and BIL (p = 0.0045), BIP and BIC (p = 0.0332), and RC and BIP (p = 0.0470). No significant differences regarding survival rates were observed between the BIL and BIC groups or between the BIP and BIL groups. With regard to the number of inflamed samples per group, a statistically significant difference was observed between the BIC and RC groups and the BIL and RC groups (p = 0.05). Carbon dioxide pneumoperitoneum has a protective effect against bacterial peritonitis induced in rats.

Impact of Stent-Graft Oversizing on the Thoracic Aorta: Experimental Study in a Porcine Model

Purpose: To analyze in an experimental animal model the effect of 4 different levels of stents-graft oversizing on non-atherosclerotic aortas such as those found in young individuals who undergo stent-graft repair for traumatic aortic injuries. Methods: The diameter of the porcine thoracic aorta is similar to the aorta of young adults (18-20 mm), so 25 pigs were randomized into 5 groups: 1 control (without stent-graft) and 4 oversizing groups (A: 10%-19%, B: 20%-29%, C: 30%-39%, and D: >40%). Two types of biomechanical tests were performed on all aortas 4 weeks after endoprosthesis deployment. Results: The results of the detachment test, which analyzed the strength necessary to remove the stent-graft from the aorta, were similar in the 4 groups (A: 42 N, B: 41 N, C: 46 N, and D: 46 N). However, 2 aortas ruptured during the tests (groups C and D). The second test was performed in 3 aortic segments. Maximum shear strength, maximum stress, and maximum tension supported by the aortic wall had a negative and linear correlation with oversizing. There were significant differences in all 4 groups when compared with the control group. Strain, which reflects the elastic properties of the aortic wall, was very similar in all 4 groups, but a great difference was found when compared with the control group (p<0.0001). Conclusion: The study showed an important subacute change in the biomechanical properties of the aortic wall after implantation of an oversized endoprosthesis. This weakness of the aortic wall was confirmed by 2 ruptures during the detachment test. These results partially explain the interaction of stent-grafts with non-atherosclerotic thoracic aortas and may serve as a basis for further studies and the development of specific material to be used in vascular trauma and young patients. J Endovasc Ther. 2011; 18: 576-584

Effect of the bilateral hip bone density measurement on clinical practice in elderly subjects

Objectives: The aim of this study was to determine whether the addition of the measurement of bilateral hip bone mineral density (BMD) has an impact on indications for osteoporosis (OP) treatment in community-dwelling elderly individuals, based on criteria from the National Osteoporosis Foundation (NOF). Methods: In total, 605 consecutive community-dwelling elderly individuals who were 65 years and older were evaluated. Dual energy X-ray absorptiometry was used to determine the lowest T-score in the lumbar spine + unilateral hip, the bilateral hips, and the lumbar spine + bilateral hips. Risk factors associated with the lowest T-score in these three conditions were applied to indicate treatment in accordance with NOF criteria. McNemar`s test was used to assess the difference of adding bilateral hip BMD measurements. Results: There was a significant difference in the frequency of pharmacological indication using NOF criteria together with the lowest T-score for the three tests (72.8% for lumbar spine + bilateral hips and 71.2% for lumbar spine + unilateral hip; p=0.002). A higher frequency of treatment indication was also observed for lumbar spine + unilateral hip (71.2%) compared to bilateral hips (61.1%) (p<0.001). The discrepancies in treatment appeared to be more evident in women when analyzed by gender distribution. Conclusion: Our finding supports the theory that evaluation of the bilateral hips with the lumbar spine seems to be more sensitive measure for identifying patients with an osteoporosis treatment indication. Furthermore, despite the well-known artifact in the lumbar spine, this site should not be excluded when determining the indication for OP treatment in elderly people. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

Effect of Severe Dietary Magnesium Deficiency on Systemic Bone Density and Removal Torque of Osseointegrated Implants

Purpose This study evaluated the effect of severe magnesium (Mg) dietary deficiency on systemic bone density and biomechanical resistance of bone tissue to the removal torque of osseointegrated implants Materials and Methods The sample consisted of 45 rats, each received a titanium implant in their tibial metaphysis After 60 days, the animals were divided into three groups (n = 15) according to their dietary Mg the control group received the recommended content of Mg, group Mg1 received a 75% reduction in dietary Mg content, and group Mg2 was fed a diet with a 90% reduction in Mg con tent Animals were sacrificed 150 days after implant placement Serum concentrations of Mg were measured and the effect of Mg deficiency on systemic bone density was evaluated by densitometry of the lumbar vertebrae and femur Biomechanical characteristics were measured by resistance of the bone tissue to removal of the implants Results Lower Mg serum concentrations were found for the Mg1 and Mg2 groups, however, densitometric analysis and torque evaluations showed a statistically significant difference only in the Mg2 group (P < 05) There was a statistically significant difference in removal torque between the Mg2 group and the control group Conclusions This study showed that a severe deficiency of Mg decreased the systemic bone density and removal torque of osseointegrated implants INT J ORAL MAXILLOFAC IMPLANTS 2010 25 1125-1130

Beneficial Effect of Creatine Supplementation in Knee Osteoarthritis

NEVES JR., M., B. GUALANO, H. ROSCHEL, R. FULLER, F. B. BENATTI, A. L. DE SA PINTO, F. R. LIMA, R. M. PEREIRA, A. H. LANCHA JR., E. BONFA. Beneficial Effect of Creatine Supplementation in Knee Osteoarthritis. Med. Sci. Sports Exerc., Vol. 43, No. 8, pp. 1538-1543, 2011. Introduction: The aim of this study was to investigate the efficacy of creatine (CR) supplementation combined with strengthening exercises in knee osteoarthritis (OA). Methods: A randomized, double-blind, placebo-controlled trial was performed. Postmenopausal women with knee OA were allocated to receive either CR (20 g.d(-1) for 1 wk and 5 g.d(-1) thereafter) or placebo (PL) and were enrolled in a lower limb resistance training program. They were assessed at baseline (PRE) and after 12 wk (POST). The primary outcome was the physical function as measured by the timed-stands test. Secondary outcomes included lean mass, quality of life, pain, stiffness, and muscle strength. Results: Physical function was significantly improved only in the CR group (P = 0.006). In addition, a significant between-group difference was observed (CR: PRE = 15.7 +/- 1.4, POST = 18.1 +/- 1.8; PL: PRE = 15.0 +/- 1.8, POST = 15.2 +/- 1.2; P = 0.004). The CR group also presented improvements in physical function and stiffness subscales as evaluated by the Western Ontario and McMaster Universities Osteoarthritis Index (P = 0.005 and P = 0.024, respectively), whereas the PL group did not show any significant changes in these parameters (P > 0.05). In addition, only the CR group presented a significant improvement in lower limb lean mass (P = 0.04) as well as in quality of life (P = 0.01). Both CR and PL groups demonstrated significant reductions in pain (P G 0.05). Similarly, a main effect for time revealed an increase in leg-press one-repetition maximum (P = 0.005) with no significant differences between groups (P = 0.81). Conclusions: CR supplementation improves physical function, lower limb lean mass, and quality of life in postmenopausal women with knee OA undergoing strengthening exercises.

The placebo effect and homeopathy

Background: Like other forms of medicine, including Complementary and Alternative Medicine (CAM), homeopathy elicits expectations in patients. The physician-patient relationship, personal and comprehensive treatment and lack of adverse effects are elements in creating positive expectations. Other elements may be associated with negative expectations. Methods: We conducted a systematic literature review on placebo and nocebo effects in acupuncture and homeopathy using Medline. Results: Findings on the psychophysiological and neuromediating mechanisms of the placebo-nocebo phenomenon are reviewed. Studies of these effects reveal how expectations and unconscious conditioning can be measured by imaging and EEG methods. They result in significant, non-specific therapeutic effects, which may confuse the evaluation of the specific therapeutic effects treatment, hampering selection of the simillimum. Conclusions: Directions for future research on non-specific therapeutic effects of homeopathy to improve clinical practice and clinical research are discussed. Homeopathy (2010) 99, 119-129.

Maternal smoking during pregnancy: Impact on otoacoustic emissions in neonates

Objectives: To determine the effect of maternal smoking during pregnancy on transient evoked otoacoustic emissions levels in neonates. Methods: This was a cross-sectional study investigating neonates in the maternity ward of a university hospital in the city of Sao Paulo, Brazil. A total of 418 term neonates without prenatal or perinatal complications were evaluated. The neonates were divided into two groups: a study group, which comprised 98 neonates born to mothers who had smoked during pregnancy; and a control group, which comprised 320 neonates born to mothers who had not. In order to compare the two ears and the two groups in terms of the mean overall response and the mean transient evoked otoacoustic emissions in response to acoustic stimuli delivered at different frequencies, we used analysis of variance with repeated measures. Results: The mean overall response and the mean frequency-specific response levels were lower in the neonates in the study group (p < 0.001). The mean difference between the groups was 2.47 dB sound pressure level (95% confidence interval: 1.47-3.48). Conclusions: Maternal smoking during pregnancy had a negative effect on cochlear function, as determined by otoacoustic emissions testing. Therefore, pregnant women should be warned of this additional hazard of smoking. It is important that smoking control be viewed as a public health priority and that strategies for treating tobacco dependence be devised. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

Effect of aquatic respiratory exercise-based program in patients with fibromyalgia

Objective: This study assessed the effects of an aquatic respiratory exercise-based program in patients with fibromyalgia (FMS). Methods: Forty women, aged between 20 and 60 years, were randomly assigned into two groups of 20 patients: the aquatic respiratory exercise-based program (ARG) and the control group (CTL). The ARG group performed the exercise program for 1 h, four times a week, for 4 weeks which included: (i) warming-Lip; (ii) respiratory exercises, consisting of five different breathing patterns, along With upper, lower limbs and trunk movements (45 min); and (iii) relaxation exercises. Both groups were included in supervised recreational activities of 1 h, once a week, for 4 weeks. Questionnaires were applied before and after intervention to assess quality of life and functional capacity (SF-36, Fibromyalgia Impact Questionnaire [FIQ]), anxiety (Hamilton Anxiety Scale [HAS]), and quality of sleep (Pittsburg Sleep Quality Index [PSQI]). Number of tender points and pain (Visual Analogue Scale [VAS]) were also evaluated. Results: At baseline there was no difference between the two groups, including number of tender points and questionnaire responses. After intervention, the ARG group, compared with the CTL group, showed improvement in SF-36 scores (physical functioning P = 0.001, bodily pain 1) = 0.001, vitality P = 0.009, social functioning P = 0.001, emotional role P = 0.001), in FIQ (total score P = 0.049, work missed P = 0.036, fatigue P = 0.013, morning tiredness P = 0.007) plus in VAS-pain (P = 0.029), VAS-dyspnea (P = 0.04), anxiety (HAS P = 0.005) and quality of sleep (PSQI P = 0.004). Conclusions: The short-term aquatic respiratory exercise-based program improved pain, quality of life, functional capacity, anxiety and quality of sleep in patients with FMS and may be a relevant addition to the treatment of these patients.

Additive Intraocular Pressure Reduction Effect of Fixed Combination of Maleate Timolol 0.5%/Dorzolamide 2% (Cosopt) on Monotherapy With Latanoprost (Xalatan) in Patients With Elevated Intraocular Pressure A Prospective, 4-week, Open-label, Randomized, Controlled Clinical Trial

Purpose: To evaluate the additive effect of dorzolamide/timolol fixed combination in patients under monotherapy with latanoprost. Patients and Methods: In this prospective, 4-week, randomized, open-label controlled clinical trial, patients with open-angle glaucoma or ocular hypertension, which presented at least 15% intraocular pressure (IOP) reduction after a minimum period of 15 days of monotherapy with latanoprost and whose IOP level was considered above the established target-IOP level were randomized to receive fixed combination of timolol/dorzolamide twice daily in one of eyes. The fellow eye was kept under monotherapy and was included in the control group. A modified diurnal tension curve (mDTC) followed by the water drinking test were performed in the baseline and week 4 visits to evaluate IOP profile between groups. Results: Forty-nine per-protocol patients were analyzed. After latanoprost monotherapy run-in period, IOP levels were significantly reduced (P<0.001) in both control and study groups to 15.34 +/- 2.96 mm Hg and 15.24 +/- 2.84 mm Hg (30.8% and 32.2% IOP reduction, respectively; P=0.552). At week 4, mean baseline diurnal IOP levels were 15.60 +/- 3.09 and 14.44 +/- 3.03 (7.4% difference; P=0.01). Mean baseline IOP modified diurnal tension curve peak after latanoprost run-in period were 17.47 +/- 3.68 mm Hg and 17.02 +/- 3.35 mm Hg (control and study eyes, respectively; P=0.530). At week 4 visit, mean water-drinking test peaks were significantly reduced in the study eye group in comparison with the control group: 19.02 +/- 3.81 mm Hg and 20.39 +/- 4.19 mm Hg, respectively (6.7% reduction; P=0.039). Conclusions: In our sample, dorzolamide 2%/timolol 0.5% fixed combination as add-on therapy in patients with open-angle glaucoma or ocular hypertension under monotherapy with latanoprost with IOP already in mid-teens levels may further enhance pressure reduction.

Trypan blue staining for capsulorhexis: Ultrastructural effect on lens epithelial cells and capsules

PURPOSE: To evaluate the ultrastructural effect of trypan blue 0.1% staining for capsulorhexis on lens epithelial cells (LECs) and capsules SETTING: Division of Ophthalmology. University of Sao Paulo, Sao Paulo, Brazil METHODS: Before capsulorhexis, patients were randomly assigned to 1 of 2 groups Trypan blue 0 1% staining was performed in the treatment group No trypan blue was used in the control group Samples of capsules with LECs were fixed and analyzed with routine optical microscopy techniques. immunohistochemistry for beclin-1 expression (a marker of autophagy), terminal deoxynucleotidyl transf erase-mediated dUTP-biotin nick-end labeling to detect apoptosis, and transmission electron microscopy (TEM) Morphometric analyses were performed. and the 2 sets of data were compared. RESULTS: Each group comprised 15 patients Cell death by autophagy and apoptosis was observed in the treatment group but not in the control group The TEM images of subcapsular epithelium cells showed mitochondria` rupture, dilation of the cisterns of the endoplasmic reticulum, increased cytoplasmic and nuclear electron density, and abnormalities in the nuclear profile of trypan blue-stained cells. Morphometric analysis showed statistically significant differences between the 2 groups in the longest nuclear axes and the ratio between the total nuclear perimeter and the cell area (P = .03) The difference in capsule thickness between groups was not significant. CONCLUSION: Trypan blue caused LEC death, which supports the hypothesis that staining with trypan blue 0 1% can help reduce the incidence of posterior capsule pacification after cataract surgery

Synergistic effect of ethanol and mitomycin C on corneal stroma

PURPOSE: To investigate the combined effects of ethanol and mitomycin C (MMC) application on the corneal stroma of rabbits that underwent photorefractive keratectomy (PRK). METHODS: Twenty-four rabbits (24 eyes) underwent PRK to correct -9.00 diopters of myopia. Twelve eyes had ethanol application before removing the epithelium and 12 eyes had the epithelium manually removed without ethanol, Eyes in both groups had topical MMC 0.02% application for 12 seconds immediately after excimer laser ablation. Twelve rabbits were sacrificed at two time points-4 hours and 4 weeks after surgery-and immunohistochemistry was performed with TUNEL assay, alpha-smooth muscle actin (alpha-SMA), and DAPI. RESULTS: More TUNEL-positive cells were observed in the ethanol-treated group compared to the mechanical debridement group at 4 hours after surgery (P<.01). No significant difference in alpha-SMA-positive cells was detected, between the two groups at 4 weeks after sugery. However, decreased keratocyte density in the anterior stroma was more pronounced in the ethanol-treated group compared to the mechanical debridement (P<.02). CONCLUSIONS: Ethanol application for epithelial removal during PRK seems to produce a synergistic effect with MMC, resulting in fewer keratocytes in the anterior stroma of rabbit corneas treated with MMC and ethanol than in corneas treated with MMC alone after PRK.

Vocational rehabilitation improves cognition and negative symptoms in schizophrenia

Several studies in schizophrenia found a positive association between cognitive performance and work status, and it has been reported that good cognitive performance at the outset does predict the success of vocational interventions. However little has been done to investigate whether vocational interventions itself benefit cognitive performance. To test this hypothesis we performed a randomized, placebo-controlled trial to investigate in remitted schizophrenic patients the effect of a 6-months vocational rehabilitation program on cognitive performance. We recruited 112 remitted and clinically stable schizophrenic patients who aimed to enter a vocational rehabilitation program. From these, 57 immediately entered a 6-months vocational rehabilitation program, whereas the remaining 55 were allocated to a waiting-list; the latter formed our control group, which received during the 6 months out-clinic follow-up treatment. Before and after the 6-months period we assessed changes in cognitive performance through a neuropsychological test battery, as well as changes in the psychopathological status and in quality of life. We found that vocational rehabilitation significantly improved patients` performance in cognitive measures that assess executive functions (concept formation, shifting ability, flexibility, inhibitory control, and judgment and critics abilities). Moreover, after 6 months the vocational group improved significantly in the negative symptoms and in quality of life, as compared to controls. Together with results from the literature, our findings reinforce the notion that the inclusion of vocational interventions may enhance the effectiveness of therapeutic strategies for schizophrenia patients. (C) 2010 Elsevier B.V. All rights reserved.

Effect of Femtosecond Laser Energy Level on Corneal Stromal Cell Death and Inflammation

PURPOSE: To analyze the effects of variations in femtosecond laser energy level on corneal stromal cell death. and inflammatory cell influx following flap creation in a rabbit model. METHODS: Eighteen rabbits were stratified in three different groups according to level of energy applied for flap creation (six animals per group). Three different energy levels were chosen for both the lamellar and side cut; 2.7 mu J (high energy), 1.6 mu J (intermediate energy), and 0.5 mu J (low energy) with a 60 kHz, model II, femtosecond laser (IntraLase). The opposite eye of each rabbit served as a control. At the 24-hour time point after surgery, all rabbits were euthanized and the comeoscleral rims were analyzed for the levels of cell death and inflammatory cell influx with the terminal uridine deoxynucleotidyl transferase dUTP-nick end labeling (TUNEL) assay and immunocytochemistry for monocyte marker CD11b, respectively. RESULTS: The high energy group (31.9 +/- 7.1 [standard error of mean (SEM) 2.9]) had significantly more TUNEL positive cells in the central flap compared to the intermediate (22.2 +/- 1.9 [SEM 0.8], P=.004), low (17.9 +/- 4.0 [SEM 1.6], P <= .001), and control eye (0.06 +/- 0.02 [SEM 0.009], P <= .001) groups. The intermediate and low energy groups also had significantly more TUNEL positive cells than the control groups (P <= .001). The difference between the intermediate and low energy levels was not significant (P=.56). The mean for CD11b-positive cells/400x field at the flap edge was 26.1 +/- 29.3 (SEM 11.9), 5.8 +/- 4.1 (SEM 1.6), 1.6 +/- 4.1 (SEM 1.6), and 0.005 +/- 0.01 (SEM 0.005) for high energy, intermediate energy, low energy, and control groups, respectively. Only the intermediate energy group showed statistically more inflammatory cells than control eyes (P = .015), most likely due to variability between eyes. CONCLUSIONS: Higher energy levels trigger greater cell death when the femtosecond laser is used to create corneal flaps: Greater corneal inflammatory cell infiltration is observed with higher femtosecond laser energy levels. [J Refract Surg. 2009;25:869-874.] doi:10.3928/1081597X-20090917-08