Combined glucosamine and chondroitin sulfate provides functional and structural benefit in the anterior cruciate ligament transection model

Evidence that combined glucosamine sulfate and chondroitin sulfate (Gluchon) or isolated glucosamine (Glu) modifies joint damage in osteoarthritis (OA) is still lacking. We studied joint pain and cartilage damage using the anterior cruciate ligament transection (ACLT) model. Wistar rats were subjected to ACLT of the right knee ( OA) or sham operation. Groups received either Glu (500 mg/kg), Gluchon (500 mg/kg glucosamine +400 mg/kg chondroitin) or vehicle (non-treated-NT) per os starting 7 days prior to ACLT until sacrifice at 70 days. Joint pain was evaluated daily using the rat-knee joint articular incapacitation test. Structural joint damage was assessed using histology and biochemistry as the chondroitin sulfate ( CS) content of cartilage by densitometry (microgram per milligram dried cartilage), comparing to standard CS. The molar weight (Mw) of the CS samples, used as a qualitative biochemical parameter, was obtained by comparing their relative mobility on a polyacrylamide gel electrophoresis to standard CS. Gluchon, but not Glu, significantly reduced joint pain (P<0.05) compared to NT. There was an increase in CS content in the OA group (77.7 +/- 8.3 mu g/mg) compared to sham (53.5 +/- 11.2 mu g/mg) (P<0.05). The CS from OA samples had higher Mw (4:62 +/- 0:24 x 10(4) g/mol) compared to sham (4:18 +/- 0:19 x 10(4) g/mol) (P<0.05). Gluchon administration significantly reversed both the increases in CS content (54.4 +/- 12.1 mu g/mg) and Mw (4:18 +/- 0:2 x 104 g/mol) as compared to NT. Isolated Glu decreased CS content though not reaching statistical significance. Cartilage histology alterations were also significantly prevented by Gluchon administration. Gluchon provides clinical (analgesia) and structural benefits in the ACLT model. This is the first demonstration that biochemical alterations occurring in parallel to histological damage in OA are prevented by Gluchon administration.

PHASE I/II STUDY OF ERLOTINIB COMBINED WITH CISPLATIN AND RADIOTHERAPY IN PATIENTS WITH LOCALLY ADVANCED SQUAMOUS CELL CARCINOMA OF THE HEAD AND NECK

Purpose: Erlotinib, an oral tyrosine kinase inhibitor, is active against head-and-neck squamous cell carcinoma (HNSCC) and possibly has a synergistic interaction with chemotherapy and radiotherapy. We investigated the safety and efficacy of erlotinib added to cisplatin and radiotherapy in locally advanced HNSCC. Methods and Materials: In this Phase I/II trial 100 mg/m(2) of cisplatin was administered on Days 8, 29, and 50, and radiotherapy at 70 Gy was started on Day 8. During Phase I, the erlotinib dose was escalated (50 mg, 100 mg, and 150 mg) in consecutive cohorts of 3 patients, starting on Day 1 and continuing during radiotherapy. Dose-limiting toxicity was defined as any Grade 4 event requiring radiotherapy interruptions. Phase 11 was initiated 8 weeks after the last Phase I enrollment. Results: The study accrued 9 patients in Phase I and 28 in Phase II; all were evaluable for efficacy and safety. No dose-limiting toxicity occurred in Phase I, and the recommended Phase 11 dose was 150 mg. The most frequent nonhematologic toxicities were nausea/vomiting, dysphagia, stomatitis, xerostomia and in-field dermatitis, acneiform rash, and diarrhea. Of the 31 patients receiving a 150-mg daily dose of erlotinib, 23 (74%; 95% confidence interval, 56.8%-86.3%) had a complete response, 3 were disease free after salvage surgery, 4 had inoperable residual disease, and 1 died of sepsis during treatment. With a median 37 months` follow-up, the 3-year progression-free and overall survival rates were 61% and 72%, respectively. Conclusions: This combination appears safe, has encouraging activity, and deserves further studies in locally advanced HNSCC. (C) 2010 Elsevier Inc.

BIOMECHANICAL EVALUATION OF ORTHOPAEDIC CEMENT COMBINED WITH ANTIBIOTIC AND METHYLENE BLUE

Objective: Acrylic cement has been used for years on orthopaedic surgeries, especially on knee arthroplasties, deserving special attention when added to antibiotics (for treatment of deep bone infections) or stains (to facilitate its removal). The present study was conducted in order to evaluate potential mechanical differences between the orthopaedic cement itself and when this is added to antibiotic and/or stains. Methods: Surgical bone cement Simplex@P Stryker, vancomycin and methylene blue were used, and the mixtures were submitted to physical and mechanical tests according the ABNT NBR ISO 5833 rule. The parameters studied here were: time for mass formation, intrusion capability, resistance to compression, resistance to flexion and maximum temperature reached by the mixtures. Results: The evaluated mixtures were approved as to mass formation, maximum temperature, intrusion capability and resistance to compression. Only the one containing pure cement was approved on the flexion essay. Conclusion: The addition of vancomycin and/or methylene blue to Surgical Simplex@P Stryker bone cement reduces its resistance to flexion, being unacceptable by the ABNT NBR ISO 5833 rule.

Effects of the addition of methyltestosterone to combined hormone therapy with estrogens and progestogens on sexual energy and on orgasm in postmenopausal women

Objective To evaluate the effect of the addition of methyltestosterone to estrogen and progestogen therapy on postmenopausal sexual energy and orgasm. Methods Sixty postmenopausal women in a stable relationship with a partner capable of intercourse, and presenting sexual complaints that appeared after menopause, were randomly divided into two groups: EP (n=29) received one tablet of equine estrogens (CEE) 0.625mg plus medroxyprogesterone acetate (MPA) 2.5mg and one capsule of placebo; EP+A (n=31) received one tablet of CEE 0.625mg plus MPA 2.5mg and one capsule of methyltestosterone 2.0mg; The treatment period was 12 months. The effects of treatment on sexual energy were assessed using the Sexual Energy Change Scale. The ability to reach orgasm in sexual relations with the partner was verified through monthly calendars and by calculating the ratio between monthly frequency of orgasms in sexual relations and monthly sexual frequency. Results There was a significant relationship between improvement in level of sexual energy and the addition of methyltestosterone to CEE/MPA treatment (p=0.021). No significant effect on orgasmic capacity was noted after the treatment period. Conclusion Addition of methyltestosterone to CEE/MPA therapy may increase sexual energy, but might not affect the ability to obtain orgasm in sexual relations.

Tentorial Posterior Fossa Meningioma Which Is the Ideal Surgical Approach: Supra/Infratentorial Combined or Retrosigmoid?

Tentorial meningiomas account for 2% to 3% of all intracranial meningiomas. The authors present their experience with posterior fossa tentorial meningiomas, and discuss the main features, which influence approaches and complications of the different surgical techniques. Twenty-four patients had meningiomas localized predominantly in posterior fossa. Their historical records and radiologic examinations were reviewed in accordance with Simpson`s classification. The extension of tumor removal was Simpson grade I in 12 patients (50%), grade II in 12 patients (50%), and grades III and IV in none of the patients. In 22 patients (91.66%), the meningioma was classified as grade I and in 2 cases (8.33%) classified as grade 11 (atypical meningioma). The combined supra/infiratentorial was employed in 12 cases, and complete resections were most common with this approach compared with retrosigmoid technique. Postoperative complications occurred in 10 patients (41.6%) with major deficits in 3 patients (12.5%). The authors believe that careful preoperative choice of the surgical approach should be based Oil tumor location and extension. It is then possible to achieve the best radical microsurgical tumor resection, avoiding additional injury to neurovascular structures.

High frequency of submicroscopic chromosomal imbalances in patients with syndromic craniosynostosis detected by a combined approach of microsatellite segregation analysis, multiplex ligation-dependent probe amplification and array-based comparative genome hybridisation

We present the first comprehensive study, to our knowledge, on genomic chromosomal analysis in syndromic craniosynostosis. In total, 45 patients with craniosynostotic disorders were screened with a variety of methods including conventional karyotype, microsatellite segregation analysis, subtelomeric multiplex ligation-dependent probe amplification) and whole-genome array-based comparative genome hybridisation. Causative abnormalities were present in 42.2% (19/45) of the samples, and 27.8% (10/36) of the patients with normal conventional karyotype carried submicroscopic imbalances. Our results include a wide variety of imbalances and point to novel chromosomal regions associated with craniosynostosis. The high incidence of pure duplications or trisomies suggests that these are important mechanisms in craniosynostosis, particularly in cases involving the metopic suture.

Nonsurgical Periodontal Therapy Combined with Laser and Photodynamic Therapies for Periodontal Disease in Immunosuppressed Rats

Background. Periodontal disease is often associated with systemic diseases and is characterized by destruction of the tissues supporting the teeth. Patients using immunosuppressive drugs such as tacrolimus are among those who suffer from tissue destruction. Objective. We sought to evaluate the effects of laser and photodynamic therapies (PDT; nonsurgical) as an adjunct to scaling and rootplaning (SRP) in the treatment of corona-induced periodontitis in rats immunosuppressed with tacrolimus (Prograf). Materials and Methods. The animals were divided into 5 groups. Each groups had 6 rats. Group I, the control group, received only saline solution throughout the study period of 42 days and did not receive periodontal treatment; group II received saline solution and SRP; group III received tacrolimus (1 mg/kg per day) and was treated with SRP; group IV animals were treated identically to group III and then administered laser treatment; and in group V, the animals were treated identically to group III and then administered PDT. Results. Statistical analysis indicated decreased bone loss with the progression of time (P = .035). There was no difference between the bone loss associated with the types of treatment administered to groups I, II, and III (P > .9) or groups IV and V (P > .6). The analysis also indicated that immunosuppression was not a bone loss-determining factor. Conclusion. Laser and PDT therapies were effective as an adjunctive treatment to SRP in reducing bone loss caused by experimental periodontitis induced in animals being treated systemically with tacrolimus.

CpG-ODN combined with Neospora caninum lysate, but not with excreted-secreted antigen, enhances protection against infection in mice

CpG oligodeoxynucleotides (ODN) have shown to be potent immunoadjuvants for several pathogens, but there is limited information concerning their use in immunization protocols against neosporosis. This study aimed to evaluate the potential of CpG-ODN combined with Neosporar lysate antigen (NLA) or excreted-secreted antigen (NcESA) to induce protective immune response against Neospora caninum infection in mice. C57BL/6 mice were vaccinated subcutaneously three times at 2-week intervals with NLA, NLA+CpG, NcESA, NcESA+CpG, CpG (adjuvant control) or PBS (infection control). Serological assays showed an increased specific IgG2a response in animals immunized with either antigen plus adjuvant and elevated levels of the IgG1 isotype in those vaccinated with antigens alone. Splenocyte proliferative responses upon antigen stimulation were higher in groups immunized with NLA OF NcESA combined with CpG, showing increased IL-12 levels. Also, mice vaccinated with NcESA or NcESA+CpG demonstrated higher IFN-gamma levels and IFN-gamma/IL-10 ratio. After lethal challenge, mice immunized with NLA+CpG or NLA had lower Morbidity score and body weight changes in comparison to other groups, and animals did not succumb during acute infection. In contrast, NcESA+CpG or NcESA groups exhibited the highest morbidity scores, body weight impairment and mortality rates, associated with greatest brain parasite burden and inflammation. In conclusion, CpG-ODN was able to induce a Th1-type humoral immune response with predominant IgG2a levels for either NLA or NcESA, but resulting in an effective Th1-driven cellular immune response and total Protection only when combined with NLA. Vaccination with NcESA alone or combined with CpG resulted in a strong cellular immune response associated with high levels of IFN-gamma and inflammation, rendering mice more susceptible to parasite challenge. (C) 2009 Elsevier Ltd. All rights reserved.

A combined study of behavior and Fos expression in limbic structures after re-testing Wistar rats in the elevated plus-maze

The elevated plus-maze is an animal model used to study anxiety. In a second session, rats show a reduction in the exploratory behavior even when the two sessions are separated by intervals as large as 7 days. The aim of the present study was to investigate whether the reduction in the exploratory behavior is maintained after intervals larger than 7 days. Additionally, we aimed at investigating eventual correlations between behaviors in the plus-maze and activation of limbic structures as measured by Fos protein expression after the second session. Rats were tested for 5 min in the elevated plus-maze and re-tested 3, 9 or 33 days later. Other groups were tested only once. The rat brains were processed for immunohistochemical detection of Fos protein. The results show a decrease in the open arms exploration in the second trial with intervals of 3, 9 and 33 days. The expression of Fos protein in the piriform cortex, septal nucleus and paraventricular hypothalamic nucleus in the groups tested with intervals of 9 and 33 days were statistically different from the other groups. The alterations observed in exploratory behavior in the second session in the plus-maze did not correlate with Fos expression. In conclusion, although the specific test conditions were sufficient to evoke behavioral alterations in exploration in the elevated plus-maze, they were enough to induce significant Fos protein expression in piriform cortex, septal nucleus and thalamic and hypothalamic paraventricular nuclei but not in other areas such as dorsomedial nucleus of the hypothalamus and amygdala nuclei, known to be also active participants in circuits controlling fear and anxiety. (C) 2010 Elsevier Inc. All rights reserved.

Effect of low-dose combined oral contraceptive on aerobic capacity and anaerobic threshold level in active and sedentary young women

Background: The purpose of this study was to evaluate the effect of long-term use of oral contraceptives (DC) containing 0.20 mg of ethinylestradiol (EE) combined with 0.15 mg of gestodene (GEST) on the peak aerobic capacity and at the anaerobic threshold (AT) level in active and sedentary young women. Study Design: Eighty-eight women (23 +/- 2.1 years old) were divided into four groups active-OC (G1), active-NOC (G2), sedentary-OC (G3) and sedentary-NOC (G4) and were submitted to a continuous ergospirometric incremental test on a cycloergometer with 20 to 25 W min(-1) increments. Data were analyzed by two-way ANOVA with Tukey post hoc test. Level of significance was set at 5%. Results: The OC use effect for the variables relative and absolute oxygen uptake VO(2) mL kg(-1) min(-1); VO(2), L min(-1), respectively), carbon dioxide output (VCO(2), L min(-1)), ventilation (VE, L min(-1)), heart rate (HR, bpm), respiratory exchange ratio (RER) and power output (W) data, as well as the interaction between OC use and exercise effect on the peak of test and at the AT level did not differ significantly between the active groups (G1 and G2) and the sedentary groups (G3 and G4). As to the exercise effect, for all variables studied, it was noted that the active groups presented higher values for the variables VO(2), VCO(2), VE and power output (p<.05) than the sedentary groups. The RER and HR were similar (p>.05) at the peak and at the AT level between G1 vs. G3 and G2 vs. G4. Conclusions: Long-term use of OC containing EE 0.20 mg plus GEST 0.15 mg does not affect aerobic capacity at the peak and at the AT level of exercise tests. (C) 2010 Elsevier Inc. All rights reserved.

Both a combined oral contraceptive and depot medroxyprogesterone acetate impair endothelial function in young women

Background: The study was conducted to determine whether the use of a combined oral contraceptive (COC) or depot medroxyprogesterone acetate (DMPA) interferes with endothelial function. Study Design: The study was conducted on 100 women between the ages of 18 and 30 years. Fifty women had not used hormonal contraception (control group) for at least 12 months, 25 were current users of a COC (ethinylestradiol 30 mcg+levonorgestrel 150 mcg) and 25 were current users of DMPA (150 mg) for at least a 6-month period. All women were evaluated for brachial flow-mediated dilation (FMD), intima-media thickness, carotid distensibility and stiffness index, arterial pressure, body mass index, waist circumference, heart rate and lipid profile. Results: A significant difference in FMD was observed between the COC and control groups (6.4 +/- 2.2% vs. 8,7 +/- 3.4%, p<.01) and between the DMPA and control groups (6.2 +/- 2.1% vs. 8.7 +/- 3.4%, p<.01). The DMPA group had lower values of total cholesterol (TC) and low-density lipoprotein (LDL-C) than COC users and the control group (TC: DMPA=139.9 +/- 21.5 mg/dL vs. controls=167.1 +/- 29.2 mg/dL vs. COC=168.2 +/- 37.5. p=.001; LDL-C: DMPA-85.3 +/- 20.1 mg/dL vs. controls=102 +/- 24.5 mg/dL vs. COC=106.7 +/- 33.3 mg/dL, p=.01). The control group had higher levels of high-density lipoprotein (HDL-C) than the DMPA and COC groups (controls=52.4 +/- 14.1 mg/dL vs. DMPA=42.2 +/- 7.2 mg/dL vs. COC=45.4 +/- 9.1 mg/dL, p=.001). No significant differences were observed regarding the other variables. Conclusions: FMD was lower among COC and DMPA users, Suggesting that these hormonal contraceptives may promote endothelial dysfunction. (C) 2009 Elsevier Inc. All rights reserved.

Hemodynamic effects of inducible nitric oxide synthase inhibition combined with sildenafil during acute pulmonary embolism

While endogenous nitric oxide (NO) may be relevant to the beneficial hemodynamic effects produced by sildenafil during acute pulmonary embolism (APE), huge amounts of inducible NO synthase (iNOS)derived NO may contribute to lung injury. We hypothesized that iNOS inhibition with S-methylisothiourea could attenuate APE-induced increases in oxidative stress and pulmonary hypertension and, therefore, could improve the beneficial hemodynamic and antioxidant effects produced by sildenafil during APE. Hemodynamic evaluations were performed in non-embolized dogs treated with saline (n = 4), S-methylisothiourea (0.01 mg/kg followed by 0.5 mg/kg/h, n = 4), sildenafil (0.3 mg/kg, n = 4), or S-methylisothiourea followed by sildenafil (n = 4), and in dogs that received the same drugs and were embolized with silicon microspheres (n = 8 for each group). Plasma nitrite/nitrate (NOx) and thiobarbituric acid reactive substances (TBARS) concentrations were determined by Griess and a fluorometric assay, respectively. APE increased mean pulmonary arterial pressure (MPAP) and pulmonary vascular resistance index (PVRI) by 25 +/- 1.7 mm Hg and by 941 +/- 34 dyn s cm(-5) m(-2), respectively. S-methylisothiourea neither attenuated APE-induced pulmonary hypertension, nor enhanced the beneficial hemodynamic effects produced by sildenafil after APE (>50% reduction in pulmonary vascular resistance). While sildenafil produced no change in plasma NOx concentrations, S-methylisothiourea alone or combined with sildenafil blunted APE-induced increases in NOx concentrations. Both drugs, either alone or combined, produced antioxidant effects. In conclusion, although iNOS-derived NO may play a key role in APE-induced oxidative stress, our results suggest that the iNOS inhibitor S-methylisothiourea neither attenuates APE-induced pulmonary hypertension, nor enhances the beneficial hemodynamic effects produced by sildenafil. (C) 2010 Elsevier Inc. All rights reserved.

Cross-Sectional Microhardness of Human Enamel Subjected to Erosive, Cariogenic or Combined Erosive/Cariogenic Challenges

This in situ study evaluated the interaction between caries and erosion processes. In the first phase, enamel specimens were subjected to erosion without dental plaque (EO) or to erosion with plaque (EP); in the second phase, they were subjected to erosion plus cariogenic challenge (EC) or cariogenic challenge (CO), both with plaque accumulation. Cross-sectional hardness data (10-330 mu m depth) were tested using ANOVA (alpha = 0.05). EO and EP showed surface softening to 10 mu m depth. CO and EC produced subsurface lesions, of similar depth (up to 220 mu m), with CO showing higher integrated loss of hardness than EC, indicating that cariogenic and erosive challenges did not have an additive effect. Copyright (C) 2010 S. Karger AG, Basel