Adrenalectomy counteracts the local modulation of astroglial fibroblast growth factor system without interfering with the pattern of 6-OHDA-induced dopamine degeneration in regions of the ventral midbrain

The present study investigated the effects of bilateral adrenalectomy (ADX) on the synthesis of basic fibroblast growth factor (bFGF, FGF-2) mRNA and on the expression of its FGF receptor subtype-2 (FGFR2) mRNA after a 6-hydroxydopamine (6-OHDA)-induced lesion of nigrostriatal dopamine system. In previous papers we have demonstrated that corticosterone increases FGF-2 immunoreactivity mainly in the astrocytes of the substantia nigra [Chadi, G., Rosen, L., Cintra, A., Tinner, B., Zoli, M., Pettersson, R.F., Fuxe, K., 1993b. Corticosterone increases FGF-2 (bFGF) immunoreactivity in the substantia nigra of the rat. Neuroreport 4, 783-786.] and that 6-OHDA injected in the ventral midbrain upregulates FGF-2 synthesis in reactive astrocytes in the ascending dopamine pathways [Chadi, G., Cao, Y., Pettersson, R.F., Fuxe, K., 1994. Temporal and spatial increase of astroglial basic fibroblast growth factor synthesis after 6-hydroxydopamine-induced degeneration of the nigrostriatal dopamine neurons. Neuroscience 61, 891-910.]. Rats were adrenalectomized and received a 6-OHDA stereotaxical injection in the ventral midbrain 2 days later. Seven days after the dopamine lesion, Western blot analysis showed a decreased level of tyrosine hydroxylase in the lesioned side of the midbrain, an event that was not altered by ADX or corticosterone replacement. Moreover, the degeneration of nigral dopamine neurons, which was confirmed by the disappearance of acidic FGF (FGF-1) mRNA and the decrement of tyrosine hydroxylase mRNA labeled nigral neurons, was not altered by ADX. The FGF-2 protein (23 kDa isoform but not 21 kDa fraction) levels increased in the lesioned side of the ventral midbrain. This elevation was counteracted by ADX, an effect that was fully reversed by corticosterone replacement. In situ hybridization revealed that ADX counteracted the elevated FGF-2 mRNA levels in putative glial cells of the ipsilateral pars compacta of the substantia nigra and in the ventral tegmental area. The ADX also counteracted the increased density and intensity of the astroglial FGF-2 immunoreactive profiles within the lesioned pars compacta of the substantia nigra and the ventral tegmental area as determined by stereology. The stereotaxical mechanical needle insertion triggered the expression of FGFR2 mRNA in putative glial cells, spreading to the entire ipsilateral ventral midbrain from the region of needle track, an occurrence that was partially reversed by ADX. In conclusion, bilateral ADX counteracted the increased astroglial FGF-2 synthesis in the dopamine regions of the ventral midbrain following a 6-OHDA-induced local lesion and interfered with FGF receptor regulation around injury. These findings give further evidence that adrenocortical hormones may regulate the astroglial FGF-2-mediated trophic mechanisms and wound repair events in the lesioned central nervous system. (c) 2007 Elsevier B.V. All rights reserved.

Transdermal estrogen therapy effects on fibrinogen levels in women with a past history of venous thromboembolism: a pilot study

Objective: To evaluate thromboelastographic parameters and fibrinogen levels in women treated with transdermal 17 beta estradiol. Methods: 29 menopausal women with a history of venous thromboembolic disease were included. Nine patients composed the treatment (HT) group and 20 the control group. Coagulation was assessed by thromboelastography in samples of whole blood and platelet-poor plasma (PPP). The following thromboelastographic variables were measured: time for initial coagulation (R), blood clotting speed (K and the a angle), clot tensile strength (MA and G), global index of coagulation (Cl) and fibrinolysis (LY30) and fibrinogen levels. Results: There were no differences in the other parameters comparing both groups. Fibrinogen levels showed a 13.77 +/- 19.94% reduction in the HT group and a 5.51 +/- 8.09% increase in the control group after 6 months. Conclusions: Our data suggested that transdermal estrogen may not increase blood coagulability, but that it reduces fibrinogen levels in FIT women.

Effects of metoclopramide-induced hyperprolactinemia on the prolactin receptor of murine endometrium

Objective: To evaluate the effects of metoclopramide-induced hyperprolactinemia, on the prolactin receptor of murine endometrium. Design: Experimental study using the RNA extraction to detect tissue prolactin recepter isoforms by reverse-transcriptase polymerase chain reaction (RT-PCR). Setting: University-based laboratory. Animal(s): Seventy-two female swiss albino mice (Mus musculus), approximately 100 days old, were divided into six 12-animal groups: (Cl) nonoophorectomized mice given vehicle; (GII) nonoophorectomized mice treated with metoclopramide; (Gill) oophorectomized mice treated with metoclopramide; (GIV)oophorectomized mice treated with metoclopramide and 17 beta-estradiol; (GV) oophorectomized mice treated with metoclopramide and micronized progesterone; (GVI) oophorectomized mice treated with metoclopramide and a solution of 17 beta-estradiol and micronized progesterone. Intervention(s): Drugs were administered for 50 days. Following euthanasia, the middle portions of the uterine horns were removed, sectioned, and immediately frozen for RT-PCR procedures. Blood was collected for the dosage of prolactin and serum estrogen and progesterone using radioimmune assay. Main Outcome Measure(s): Identification of uterine prolactin receptor isoforms: Result(s): The PRL receptor and its isoform L were identified only in GI (control group) and GII (metoclopramide), the two groups with nonoophorectomized animals. The amount of PRL receptor mRNA and that of its isoform L from GII were the largest. No other isoforms of the prolactin receptor were identified in any of the groups. Conclusion(s): Our results suggest that replacement of estrogen and progestin may not increase the mRNA of endometrial PRL receptor in metoclopromide-induced hyperprolactinemia in rats after castration. (Fertil Steril (R) 2010;93:1643-9. (C)2010 by American Society for Reproductive Medicine.)

Influence of the CYP17 polymorphism on vasomotor symptoms in postmenopausal women: a pilot study

Objective To evaluate the influence of CYP17 polymorphism on menopausal symptoms after estrogen treatment. Methods A total of 130 women were recruited, but only 100 of these were selected according to inclusion and exclusion criteria; they were treated with 0.3 mg/day conjugated equine estrogens. One year later, the study was completed by 71 women. The analysis of the Kupperman menopausal index symptoms was made with information provided by the patients on daily diary cards. Blood samples were analyzed and the women were divided into two groups based on the CYP17, 5`-untranslated region: group A (wild-type homozygote and heterozygote) and group B (mutated homozygote). Results The values for the Kupperman menopausal index were similar in both groups at baseline. The symptoms in both groups decreased after 1 year of treatment when compared to those at baseline. The improvement rate was approximately 27.09% and 32.18%, in groups A and B, respectively. The levels of estrogen after treatment were higher in both groups in comparison with the baseline values. The testosterone level rose in group B with the 1-year treatment (0.48 +/- 0.16 ng/ml), reaching a higher level than the level in group A after treatment. The sex hormone binding globulin (SHBG) level showed a significant increase after the 1-year treatment in group B, surpassing both the baseline and the after-treatment values in group A (p < 0.01). Conclusion Our data suggest that the CYP17 polymorphism did not influence the action of estrogen on menopause symptoms during the 1-year treatment. The extra production of estrogen and androgen may have been countered by the elevation of SHBG levels.

Effects of estradiol and norethisterone on lipids, insulin resistance and carotid flow

Objectives: To evaluate the lipid profile, insulin resistance and vasomotricity, and the interaction between these factors, in postmenopausal women receiving hormone therapy. Methods: A prospective, randomized, double-blind study was carried out in which 77 postmenopausal women received one of the three treatment regimens: (A) 2 mg oral micronized estradiol (E(2)) (n = 25); (B) 2 mg oral E(2) + 1 mg oral norethisterone acetate (NETA) (n = 28); or Q placebo (n = 24), daily for 6 months. Evaluations were carried out at baseline and at the end of treatment on lipid and lipoprotein profiles, homeostasis model assessment of insulin resistance (HOMA-IR) and pulsatility index (PI) of the internal carotid artery by Doppler ultrasonography. Results: Mean increases of 15.6% and 2.4% and a reduction of 6.4% in high-density lipoprotein (HDL) levels were found for the E(2), E(2) + NETA and placebo groups, respectively. Reductions of 9.5% and 3.7% and an increase of 12.1% in low-density lipoprotein (LDL), and reductions of 20.0% and 3.8% and an increase of 28.8% in the LDL:HDL ratio were found for the E(2), E(2) + NETA and placebo groups, respectively (p < 0.001 in all cases). Insulin levels and HOMA-IR decreased 12.8% and 12.3% in the E2 group and increased 12.9% and 16.0% in the E(2) + NETA group (p < 0.05), respectively. Carotid PI following treatment was 1.18 +/- 0.23, 1.38 +/- 0.20 and 1.41 +/- 0.21 for the E(2), E(2) + NETA and placebo groups, respectively (p = 0.0006). Conclusions: Oral estrogen therapy led to an improvement in lipid profile, insulin resistance and carotid blood flow, which was cancelled when NETA was associated. (c) 2008 Elsevier Ireland Ltd. All rights reserved.

Aseptic Loosening of Total Hip Arthroplasty: Preliminary Genetic Investigation

Femoral and acetabular loosening call be attributed different factors, but the Causes and mechanism of early failure are still obscure, The objective of this Study was to investigate the relationship between gene polymorphisms and early implant failure. Fifty-eight patients older than 50 years was recruited for analysis of MMP-1 promoter polymorphisms in early osseointegrated implant failure. The results showed in control group a frequency of 20.97% of 2G allele and 67.74% the genotype 1G/1G whereas, in the test group, a frequency of 83.33% of 2G allele and 66.66% the genotype 2G/2G. These results indicate that the polymorphism ill the promoter of the MMP-1 gene could be it risk factor for early implant failure of total hip arthroplasty.

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.

Impact of Nervous System Hyperalgesia on Pain, Disability, and Quality of Life in Patients With Knee Osteoarthritis: A Controlled Analysis

Objective. Refractory, disabling pain associated with knee osteoarthritis (OA) is usually treated with total knee replacement. However, pain in these patients might be associated with central nervous sensitization rather than peripheral inflammation and injury. We evaluated the presence of hyperalgesia in patients scheduled for a total knee replacement due to knee osteoarthritis with refractory pain, and we assessed the impact of pressure pain threshold measurements (PPT) on pain, disability, and quality of life of these patients. Methods. Sixty-two female patients were compared with 22 age-matched healthy controls without reported pain for the last year. PPT was measured at the lower extremities subcutaneous dermatomes, over the vastus medialis, adductor longus, rectus femoris, vastus lateralis, tibialis anterior, peroneus longus, iliacus, quadratus lumborum and popliteus muscles and at the supraspinous ligaments from L1-L5, over the L5-S1 and S1-S2 sacral areas and at the pes anserinus bursae and patellar tendon. Results. Patients with knee OA had significantly lower PPT over all evaluated structures versus healthy control subjects (P < 0.001). Lower PPT values were correlated with higher pain intensity, higher disability scores, and with poorer quality of life, except for the role-emotional and general health status. Combined PPT values over the patellar tendon, at the S2 subcutaneous dermatome and at the adductor longus muscle were the best predictors for visual analog scale and Western Ontario and McMaster Universities Osteoarthritis Index pain scores. Conclusion. Patients with pain due to osteoarthritis who were scheduled for total knee replacement showed hyperalgesia of nervous system origin that negatively impacted pain, knee functional capacity, and most aspects of quality of life.

Neutropenia in antibody-deficient patients under IVIG replacement therapy

Patients with antibody deficiencies are more prone to develop acute neutropenic episodes even during immunoglobulin replacement. The aims of this study were to evaluate the presence of acute neutropenia in 42 patients with primary antibody immunodeficiencies, currently receiving intravenous immunoglobulin (IVIG), and to describe the clinical and laboratory findings during neutropenic episodes. Of all patients, 10 (23.8%) presented acute neutropenia (absolute neutrophil count < 1500 cells/mm(3)) during follow up (mean of 6.4 yr). The absolute neutrophil count ranged from 71 to 1488 cells/mm(3). Neutropenia was not clearly associated with antibiotic prophylactic therapy or immunoglobulin levels, while infections were associated with neutropenia in the majority of episodes. Most acute neutropenia episodes were mild or moderate, except in CVID patients who present more severe neutropenia. Although IVIG may have contributed to reducing the severity of neutropenia, it does not prevent its occurrence in all patients. In conclusion, primary immunodeficient patients, even submitted to IVIG replacement therapy, must be regularly evaluated for neutropenia in order to minimize the risk of infections and its appropriate approach.

Effects of topiramate or naltrexone on tobacco use among male alcohol-dependent outpatients

Background: A high smoking prevalence has been registered among alcoholics. It has been pointed out that alcoholic smokers may have a more severe course and greater severity of alcoholism. This study aims at comparing smoking and non-smoking alcoholics in terms of treatment outcomes and verifying the efficacy of topiramate and naltrexone to decrease the use of cigarettes among alcoholic smokers. Methods: The investigation was a double-blind, placebo-controlled, 12-week study carried out at the University of Sao Paulo, Brazil. The sample comprised 155 male alcohol-dependent outpatients (52 nonsmokers and 103 smokers). 18-60 years of age, with an International Classification of Diseases (ICD-10) diagnosis of alcohol dependence. After a 1-week detoxification period, the patients randomly received placebo, naltrexone (50 mg/day) or topiramate (up to 300 mg/day). Only the alcoholic smokers who adhered to the treatment were evaluated with reference to the smoking reduction. Results: Cox regression analysis revealed that the smoking status among alcoholics increased the odds of relapse into drinking by 65%, independently of the medications prescribed, using the intention-to-treat method. Topiramate showed effectiveness to reduce the number of cigarettes smoked when compared to placebo among adherent patients (mean difference =7.91, p < 0.01). There were no significant differences between the naltrexone group and the placebo group. Conclusions: The results of this study confirm that the treatment is more challenging for smoking alcoholics than for non-smoking ones and support the efficacy of topiramate in the smoking reduction among male alcoholic smokers who adhered to the treatment. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

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.

POLYETHYLENE GLYCOL ADDITION DOES NOT IMPROVE EXOGENOUS SURFACTANT FUNCTION IN AN EXPERIMENTAL MODEL OF MECONIUM ASPIRATION SYNDROME

Meconium (MEC) is a potent inactivator of pulmonary surfactant. The authors studied the effects of polyethylene glycol addition to the exogenous surfactant over the lung mechanics and volumes. Human meconium was administrated to newborn rabbits. Animals were ventilated for 20 minutes and dynamic compliance, ventilatory pressure, and tidal volume were recorded. Animals were randomized into 3 study groups: MEC group (without surfactant therapy); S100 group (100 mg/kg surfactant); and PEG group (100 mg/kg porcine surfactant plus 5% PEG). After ventilation, a pulmonary pressure-volume curve was built. Histological analysis was carried out to calculate the mean alveolar size (Lm) and the distortion index (DI). Both groups treated with surfactant showed higher values of dynamic pulmonary compliance and lower ventilatory pressure, compared with the MEC group (P .05). S100 group had a larger maximum lung volume, V30, compared with the MEC group (P .05). Lm and DI values were smaller in the groups treated with surfactant than in the MEC group (P .05). No differences were observed between the S100 and PEG groups. Animals treated with surfactant showed significant improvement in pulmonary function as compared to nontreated animals. PEG added to exogenous surfactant did not improve lung mechanics or volumes.

Dog culling and replacement in an area endemic for visceral leishmaniasis in Brazil

Measures employed to control visceral leishmaniasis in Brazil have focused on vector control by residual insecticide spraying and diagnosis of infection with elimination of positive dogs. We describe dog culling and replacement in a Brazilian endemic area (the Alvorada District, Aracatuba, SP) in order to better understand dog population dynamics when elimination of the dog reservoir is adopted as the main control measure. From August 2002 to July 2004, 60.9% of the estimated dog population for the area was culled with a mean age of 34 months old. The presence of anti-Leishmania sp. antibodies was recorded for only 26.7% of the euthanized canines. Replacement was observed in 38.8% of the cases, some of them by 2 or more dogs and in a mean time of 4 months. Dogs were replaced mostly by puppies of both sexes with a mean age of 6.8 months. From August 2002 to April 2005 we were able to follow-up 116 of these dogs, during a mean time of 8.7 months. Canine visceral leishmaniasis seropositivity by ELISA was observed in 42.2% of the followed dogs, 30.6% of which were already positive at the first evaluation. By the end of the follow-up period 37% of the dogs were submitted to euthanasia, with a mean age of 18.3 months. In the studied CVL endemic area of Brazil, euthanasia and the subsequent replacement ratio were high, increasing the dog population turnover and leading to a younger population that might be more susceptible to a variety of other infectious diseases in addition to CVL. Dog culling as a control strategy for VL should be reassessed. (C) 2008 Elsevier B.V. All rights reserved.

Differential Persistence of Transmitted HIV-1 Drug Resistance Mutation Classes

Methods. We studied participants with acute and/or early HIV infection and TDR in 2 cohorts (San Francisco, California, and Sao Paulo, Brazil). We followed baseline mutations longitudinally and compared replacement rates between mutation classes with use of a parametric proportional hazards model. Results. Among 75 individuals with 195 TDR mutations, M184V/I became undetectable markedly faster than did nonnucleoside reverse-transcriptase inhibitor (NNRTI) mutations (hazard ratio, 77.5; 95% confidence interval [CI], 14.7-408.2; P < .0001), while protease inhibitor and NNRTI replacement rates were similar. Higher plasma HIV-1 RNA level predicted faster mutation replacement, but this was not statistically significant (hazard ratio, 1.71 log(10) copies/mL; 95% CI, .90-3.25 log(10) copies/mL; P = .11). We found substantial person-to-person variability in mutation replacement rates not accounted for by viral load or mutation class (P < .0001). Conclusions. The rapid replacement of M184V/I mutations is consistent with known fitness costs. The long-term persistence of NNRTI and protease inhibitor mutations suggests a risk for person-to-person propagation. Host and/or viral factors not accounted for by viral load or mutation class are likely influencing mutation replacement and warrant further study.

Demographic profile of blood donors at three major Brazilian blood centers: results from the International REDS-II study, 2007 to 2008

BACKGROUND: The profile of blood donors changed dramatically in Brazil over the past 20 years, from remunerated to nonremunerated and then from replacement to community donors. Donor demographic data from three major blood centers establish current donation profiles in Brazil, serving as baseline for future analyses and tracking longitudinal changes in donor characteristics. STUDY DESIGN AND METHODS: Data were extracted from the blood center, compiled in a data warehouse, and analyzed. Population data were obtained from the Brazilian census. RESULTS: During 2007 to 2008, there were 615,379 blood donations from 410,423 donors. A total of 426,142 (69.2%) were from repeat (Rpt) donors and 189,237 (30.8%) were from first-time (FT) donors. Twenty percent of FT donors returned to donate in the period. FT donors were more likely to be younger, and Rpt donors were more likely to be community donors. All were predominantly male. Replacement donors still represent 50% of FT and 30% of Rpt donors. The mean percentage of the potentially general population who were donors was approximately 1.2% for the three centers (0.7, 1.5, and 3.1%). Adjusting for the catchment`s area, the first two were 2.1 and 1.6%. CONCLUSIONS: Donors in the three Brazilian centers tended to be younger with a higher proportion of males than in the general population. Donation rates were lower than desirable. There were substantial differences in sex, age, and community/replacement status by center. Studies on the safety, donation frequencies, and motivations of donors are in progress to orient efforts to enhance the availability of blood.