Alteration of trabecular bone under chronic beta2 agonists treatment

PURPOSE: beta2 adrenergic agonists are widely used as doping agents. Their side effects on bone, especially microarchitecture, remain unknown. The purpose of this study was to evaluate the effects of chronic clenbuterol and salbutamol treatment on bones of growing rats. METHODS: Twelve-week-old Wistar female rats were divided into three groups: salbutamol (4 mg.kg(-1).d(-1)), clenbuterol (2 mg.kg(-1).d(-1)), and normal saline (0.5 mL.kg(-1).d(-1)) and treated for 6 wk. Proximal tibia and lumbar spine L4 were analyzed by absorptiometry and by 3D microcomputed tomography. Bending and compression tests were used to measure their mechanical properties. RESULTS: After 6 wk, the salbutamol and clenbuterol groups had lower bone mineral density (BMD) in the tibia, proximal tibia, and vertebrae. Trabecular number and bone volume for the vertebrae were lower in animals treated with clenbuterol (Tb.N: -14.31%, P < 0.001; BV/TV: -21.07%, P < 0.001) or salbutamol (TbN: -12.7%, P < 0.001; BV/TV: -19.7%, P < 0.001) than in controls. Mechanical properties of the tibia were affected by clenbuterol with a lower ultimate force (P = 0.02) and a trend in lower energy to ultimate force (P = 0.053). In vertebrae, salbutamol and clenbuterol induced lower ultimate force. Clenbuterol significantly increased muscle mass (+58.83%, P < 0.01) and reduced fat mass (-28.75%, P < 0.01) compared with controls +17.07 and -7.34%, respectively. CONCLUSION: This study shows a negative effect of clenbuterol and salbutamol on the mechanical properties and microarchitecture of trabecular bone. In the clenbuterol group it was notable that the bone loss contrasts with the anabolic effect on muscle mass. Clearly an increase of muscle mass with enhanced bone fragility augments the risk of fractures for humans or animals treated with beta2 agonists as part of a doping regimen.     

Gluteal stab wound is a frequent and potentially dangerous injury

BACKGROUND: Stab wounds to the gluteal area are a frequent injury in an urban trauma centre. These injuries may appear innocuous but is potentially life threatening. Therefore they deserve timely evaluation and management. The purpose of this study was to evaluate our experience with this type of injury and to propose a treatment protocol. METHODS: During the last 5 years 269 patients with stab injuries, were admitted to our Department of Emergency Medicine (DEM). Thirty-nine patients (14%) who had gluteal penetration were included in this study. Patients' charts were retrospectively reviewed for demographic data, type of injury and additional injuries, evaluation, management and outcome. RESULTS: Stab wound of the gluteal region was the most frequent injury after chest and abdominal injuries. Thirty patients presented with soft tissue damage only and nine were severely injured. Seven of the severely injured patients had significant bleeding; two of them were treated by embolisation. One patient suffered a rectal injury and one a small bowel perforation, both treated surgically. There was no post-operative complication or mortality. CONCLUSIONS: Penetration of the gluteal is a potentially life threatening injury. Meticulous observation and high level of suspicion ensure early treatment and can prevent mortality.     

Limbal graft and/or amniotic membrane transplantation in the treatment of ocular burns

Limbal stem cell transplantation (LSCT) and amniotic membrane transplantation may improve corneal recovery after a chemical burn. Amniotic membrane was applied as a patch in 5 eyes; LSCT from healthy contralateral eye was performed in 6 eyes, and a combination of these techniques was performed in 4 eyes. There were no complications during surgical procedure. Epithelization was completed after 2 weeks in patients with LSCT, and after 3 weeks in the amniotic membrane transplantation group. Visual acuity improved in all patients. No complication was observed on either the donor or the recipient eye during a follow-up period of >13 months in all groups. Amniotic membrane is effective in promoting re-epithelization and reducing inflammation when applied alone in patients with 3- to 6-hour limbal involvement, as well as combined with LSCT in patients with >6-hour limbal ischemia. LSCT is an effective procedure for rehabilitation after severe chemical trauma of the eye with more than 50% limbal involvement.     

Pyrazolo[4,3-e]1,2,4-triazolo[1,5-c]pyrimidine ligands, new tools to characterize A3 adenosine receptors in human tumor cell lines

Increased concentrations of extracellular adenosine are reached in ischemic or inflamed tissues but have also been detected inside tumoral masses. If this finding may account for an important role of adenosine in the pathogenesis of tumors remains to be determined in view of its contradictory effects on cell survival and proliferation. In particular, adenosine was found to exert its effects on proliferation and on cell death mainly through the A(3) adenosine receptor. Therefore, a complete pharmacological characterization of the subtype and number of the expressed A(3) adenosine receptors is necessary for the elucidation of the role of adenosine via A(3) receptors in a specific cell subtype. The lack of potent and selective radiolabelled A(3) receptor antagonists has been, in the past, the major obstacle in the characterization of structure, function and regulation of this adenosine receptor subtype. Recently, our group has identified a series of substituted pyrazolotriazo-lopyrimidine derivatives as potent and selective antagonists to human A(3) adenosine receptors. The most recent results obtained in this field will be summarized in the present review. Furthermore, the review will report the results of the biochemical and pharmacological characterization of A(3) receptors in different human tumor cell lines and the multiple A(3) receptor-sustained ways that could prime tumor development.     

Combined target-based and ligand-based drug design approach as a tool to define a novel 3D-pharmacophore model of human A3 adenosine receptor antagonists: pyrazolo[4,3-e]1,2,4-triazolo[1,5-c]pyrimidine derivatives as a key study

A combined target-based and ligand-based drug design approach has been carried out to define a novel pharmacophore model of the human A(3) receptor antagonists. High throughput molecular docking and comparative molecular field analysis (CoMFA) have been used in tandem to assemble a new target based pharmacophore model. In parallel, to provide more accurate information about the putative binding site of these A(3) inhibitors, a rhodopsin-based model of the human A(3) receptor was built and a novel Y-shape binding motif has been proposed. Docking-based structure superimposition has been used to perform a quantitative study of the structure-activity relationships for binding of these pyrazolo-triazolo-pyrimidines to adenosine A(3) receptor using CoMFA. Both steric and the electrostatic contour plots obtained from the CoMFA analysis nicely fit on the hypothetical binding site obtained by molecular docking. On the basis of the combined hypothesis, we have designed, synthesized, and tested 17 new derivatives. Consistently, the predicted K(i) values were very close to the experimental values.     

Immunohistochemical study of tumor necrosis factor-alpha, matrix metalloproteinase-12, and tissue inhibitor of metalloproteinase-2 on alveolar macrophages of BALB/c mice exposed to short-term cigarette smoke

Alveolar cells were evaluated in BALB/c mice exposed to smoke from 9 cigarettes per day. The mice were sacrificed at 1, 5, and 10 days and examined by lung morphometry and immunohistochemical staining of alveolar macrophages for tumor necrosis factor (TNF)-alpha, matrix metalloproteinase (MMP)-12, and tissue inhibitor of metalloproteinase (TIMP)-2. Cigarette smoke (CS)-exposed mice showed a progressive increase in numbers of alveolar macrophages (AMs) up to 10 days. MMP-12 was increased in AMs compared to the control group. The number of AMs with TNF-alpha and TIMP-2 labeling was higher at 5 days but decreased at 10 days. Short-term CS exposure induced pulmonary inflammation with major participation of MMP-12-positive AMs.     

Infant feeding practices before implementing alternatives to prolonged breastfeeding to reduce HIV transmission through breastmilk in Abidjan, Cote d'Ivoire

The aim of this study was to describe baseline infant feeding practices in women of unknown HIV status in Abidjan, C?te d'Ivoire, before the implementation of infant feeding interventions aimed at the prevention of mother-to-child transmission of HIV through breastmilk. We conducted a cross-sectional survey in March 2000 among 225 mothers attending community-run health facilities with their own child for either immunization or weighting. All but two children had ever been breastfed, of whom 94 per cent were still being breastfed at 6 months of age. Exclusive breastfeeding was not practiced in this population since all women had given water to their child, starting in median one day after birth. Moreover, 20 per cent of the mothers had introduced infant formula in median three weeks after delivery. This study provides useful information for planning purposes in this urban African population, where exclusive breastfeeding is rare and the use of infant formula relatively common.