Oral health-care practices and dental assistance management strategies for people with autism spectrum disorder: An integrative literature review.

ABSTRACT: Autism spectrum disorder requires a careful approach from professionals and a favorable clinical environment for dental care and assistance. This article aims To perform a literature review about oral health among people with autism spectrum disorder and dental management strategies for this group. An integrative literature review was carried out in three databases, associating the descriptors: (autism or autism spectrum disorder) with (oral health or oral diseases) and (dental care or dental services). After identification and screening steps, 32 articles were included in the study. The most prevalent subjects were oral health conditions, parents' understanding and practical attitudes about oral health, treatment and management strategies, and the use of technology. The principal barriers to dental care were the scarcity of specialized professionals, unpreparedness in the referral system, poor accessibility of the clinics, and lack of specific care protocols. The world literature on the subject is scarce, and there is still a need for investment and scientific production due to the incidence of autism in the world population and the maintenance of difficulties and barriers in offering quality health care to this group.

Sphingosine Kinase-1 Is Overexpressed and Correlates with Hypoxia in Osteosarcoma: Relationship with Clinicopathological Parameters.

The Sphingosine kinase-1/Sphingosine 1-Phosphate (SphK1/S1P) signaling pathway is overexpressed in various cancers, and is instrumental for the adaptation to hypoxia in a number of solid tumor models, but no data are available in osteosarcoma. Here we report that SphK1 and the S1P1 receptor are involved in HIF-1α accumulation in hypoxic osteosarcoma cells. FTY720 (Fingolimod), which targets SphK1 and S1P1, prevented HIF-1α accumulation, and also inhibited cell proliferation in both normoxia and hypoxia unlike conventional chemotherapy. In human biopsies, a significant increase of SphK1 activity was observed in cancer compared with normal bones. In all sets of TMA samples (130 cases of osteosarcoma), immunohistochemical analysis showed the hypoxic marker GLUT-1, SphK1 and S1P1 were expressed in tumors. SphK1 correlated with the GLUT-1 suggesting that SphK1 is overexpressed and correlates with intratumoral hypoxia. No correlation was found between GLUT-1 or SphK1 and response to chemotherapy, but a statistical difference was found with increased S1P1 expression in patients with poor response in long bone osteosarcomas. Importantly, multivariate analyses showed that GLUT-1 was associated with an increased risk of death in flat bone, whereas SphK1 and S1P1 were associated with an increased risk of death in long bones.

Influence of Sociodemographic Determinants on the Hodgkin Lymphoma Baseline Characteristics in Long Survivors Patients Enrolled in the Prospective Phase 3 Trial AHL2011.

INTRODUCTION: Whereas numerous studies on several cancers describe the link between social conditions and disease severity, little is known about the social and demographic characteristics of Hodgkin lymphoma (HL) patients. At diagnosis, 10-15% of the patients in the advanced stages have a well-known poor outcome owing to their chemoresistance, but the determinants of the more advanced stages remain elusive. The objective of the present study was to decipher the potential impact of social disparities on the disease features at diagnosis and analyze how the sociodemographic patient features could impact the HL outcome of patients with advanced-stage HL enrolled in the AHL2011 trial. METHODS: This ancillary study was conducted on a cohort of patients from French centers that had recruited more than five patients in the phase III AHL2011 study (NCT0135874). Patients had to be alive at the time of the ancillary study and had to have given their consent to answer the questionnaire. Pre-treatment data (age, gender, stage, B symptoms, IPS), the treatment received, the responses to PET-CT, and the presence of serious adverse events (serious adverse events-SAEs) were all extracted from the AHL2011 trial database. Sociodemographic data-marital status, living area, level of education, socio-professional category, and professional situation-were extracted from the questionnaires. The population density at the point of diagnosis was determined based on ZIP Code, and the distance from the reference medical center was then calculated by the road network. Baseline PET acquisition was performed before any treatment. PET images at baseline were centrally reviewed. The total metabolic tumor volume (TMTV) at the baseline was calculated using a 41% SUVmax cutoff for each lesion. Progression-free survival was defined as the time from randomization to the first progression, relapse, or death from any cause or the last follow-up. The data cutoff for the analyses presented here was 31 October 2017. The progression-free survival was analyzed on an intention-to-treat basis. RESULTS: Among the 823 patients enrolled in the AHL2011 study, the questionnaire was sent to 394 patients, of whom 232 (58.9%) responded. At the time of HL diagnosis, 61.9% (N = 143) of patients declared that they were not socially isolated, 38.1% (N = 88) that they were single, 163 (71.2%) had a professional activity, and 66 (28.8%) were inactive owing to unemployment, retirement, or sick leave. Of the patients, 31.1% (N = 71) lived in a rural region, compared to 68.9% (N = 157) that lived in an urban region. The residence ZIP Code at the time of HL diagnosis was available for 163 (70%). Sociodemographic characteristics did not influence the presence of usual prognostic factors (ECOG, B symptoms, bulky mass, IPS) except for professional activity, which was associated with more frequent low IPS (0-2) (79 (48.5%) active versus 20 (30.3%) inactive patients; p = 0.012). Likewise, no correlation was observed between TMTV and sociodemographic characteristics. However, the TMTV quartile distribution was different according to the living area, with the two upper quartiles being enriched with patients living in a rural area (p = 0.008). Moreover, a negative correlation between the average number of the living area's inhabitants and TMTV (R Pearson = -0.29, p = 0.0004) was observed. CONCLUSION: This study focused on sociodemographic parameters in advanced-stage HL patients and shows that professional activity is associated with more favorable disease features (low IPS), while patients living in rural or low-populated areas are more likely to have an unfavorable HL presentation with a high tumor burden (high TMTV). These data suggest that some patient sociodemographic characteristics might impact either access to medical care or environmental exposure, leading to a higher frequency of unfavorable presentations. Further prospective sociodemographic studies are necessary to confirm these preliminary results.

Population PK-PD Modeling of Circulating Lymphocyte Dynamics in Chronic Lymphocytic Leukemia Patients Under Ibrutinib Treatment.

Ibrutinib is indicated for the treatment of chronic lymphocytic leukemia (CLL). Absolute lymphocyte count (ALC) is a clinical criterion used for the monitoring of CLL. Ibrutinib has several effects on lymphocytes, and has highly variable pharmacokinetics (PK). The objective of this work was to build a PK-pharmacodynamic (PD) model describing ALC dynamics under ibrutinib treatment in patients with CLL. ALC observations before and after ibrutinib treatment initiation in patients with CLL were included in the analysis. A population PK-PD model was developed based on physio-pharmacological knowledge. Individual PK concentrations at each hospital visit were included in the model. The association between PD parameters and lymphocytosis, and between PD parameters and response to treatment were assessed. A total of 94 patients, 658 ALC and 1,501 PK observations were included in model development. The final PK-PD model accurately described ALC dynamics for different patient profiles. It consisted in two compartments (tissues and blood circulation) with ibrutinib plasmatic concentration inducing two drug effects: stimulation of lymphocyte redistribution and death. Patients with hyperlymphocytosis had significantly higher tissues to circulation baseline lymphocyte count ratio, and lower death effect. Patients who progressed under ibrutinib had significantly lower baseline lymphocyte counts in tissues (2-fold lower) and blood (3-fold lower). The first PK-PD model for ALC in patients with CLL under ibrutinib treatment was developed. This model suggests that estimated lymphocyte counts in tissues and blood could be used as an early predictor of response in patients with CLL.

Population Pharmacokinetics of Ibrutinib and Its Dihydrodiol Metabolite in Patients with Lymphoid Malignancies.

BACKGROUND AND OBJECTIVE: Ibrutinib is used for the treatment of chronic lymphocytic leukemia and other lymphoid malignancies. The aim of this work is to develop a population pharmacokinetic model for ibrutinib and its dihydrodiol metabolite to quantify pharmacokinetic inter- and intra-individual variability, to evaluate the impact of several covariates on ibrutinib pharmacokinetic parameters, and to examine the relationship between exposure and clinical outcome. METHODS: Patients treated with ibrutinib were included in the study and followed up for 2 years. Pharmacokinetic blood samples were taken from months 1 to 12 after inclusion. Ibrutinib and dihydrodiol-ibrutinib concentrations were assessed using ultra-performance liquid chromatography tandem mass spectrometry. A population pharmacokinetic model was developed using NONMEM version 7.4. RESULTS: A total of 89 patients and 1501 plasma concentrations were included in the pharmacokinetic analysis. The best model consisted in two compartments for each molecule. Absorption was described by a sequential zero first-order process and a lag time. Ibrutinib was either metabolised into dihydrodiol-ibrutinib or excreted through other elimination routes. A link between the dosing compartment and the dihydrodiol-ibrutinib central compartment was added to assess for high first-pass hepatic metabolism. Ibrutinib clearance had 67% and 47% inter- and intra-individual variability, respectively, while dihydrodiol-ibrutinib clearance had 51% and 26% inter- and intra-individual variability, respectively. Observed ibrutinib exposure is significantly higher in patients carrying one copy of the cytochrome P450 3A4*22 variant (1167 ng.h/mL vs 743 ng.h/mL, respectively, p = 0.024). However, no covariates with a clinically relevant effect on ibrutinib or dihydrodiol-ibrutinib exposure were identified in the PK model. An external evaluation of the model was performed. Clinical outcome was expressed as the continuation or discontinuation of ibrutinib therapy 1 year after treatment initiation. Patients who had treatment discontinuation because of toxicity had significantly higher ibrutinib area under the curve (p = 0.047). No association was found between cessation of therapy due to disease progression and ibrutinib area under the curve in patients with chronic lymphocytic leukemia. For the seven patients with mantle cell lymphoma studied, an association trend was observed between disease progression and low exposure to ibrutinib. CONCLUSIONS: We present the first population pharmacokinetic model describing ibrutinib and dihydrodiol-ibrutinib concentrations simultaneously. Large inter-individual variability and substantial intra-individual variability were estimated and could not be explained by any covariate. Higher plasma exposure to ibrutinib is associated with cessation of therapy due to the occurrence of adverse events within the first year of treatment. The association between disease progression and ibrutinib exposure in patients with mantle cell lymphoma should be further investigated. TRIAL REGISTRATION: ClinicalTrials.gov no. NCT02824159.

Psychotropic drug initiation in patients diagnosed with chronic myeloid leukemia: a population-based study in France.

Psychotropic drugs (PD) are often used close to a cancer diagnosis and may be considered as a way of coping. We aimed to determine the incidence of anxiolytics, hypnotics, antidepressants, and antipsychotics initiation around a diagnosis of chronic myelogenous leukemia (CML). Population-based cohort: Data were extracted from Systeme National des données de Santé (SNDS, the French health insurance database) at the regional level (Midi-Pyrenees area, 2.9 million inhabitants). All newly diagnosed patients treated by a CML tyrosine kinase inhibitor (TKI) between 10/01/2011 and 04/01/2014 were included. Pre-CML (9 months before to 3 months before first TKI prescription-F-TKI) and CML (3 months before to 9 months after F-TKI) phases were defined. The main evaluation criterion was the initiation of PD during CML phase. Determinants associated with this incident PD use were studied through a logistic regression model. We compared pre-CML and CML healthcare consumption. The cohort included 103 patients (mean age of 60.8 years). PD initiation rate was 35.9%, anxiolytics being the most initiated PD (59.5%). Advanced age was associated with PD initiation (adjusted OR = 1.029, 95% CI = 1.001-1.056). The number of consultations during the pre-CML phase and female gender tended to be associated with increased risk of PD initiation in univariate analysis. For PD initiators, healthcare consumption was greater in CML but not in pre-CML phase. PD initiation is a frequent finding around a CML diagnosis. Its risk increases with age. It could be a way to identify a subgroup with higher healthcare consumption.

The impact of chronic myeloid leukemia on employment: the French prospective study.

Patients with chronic myeloid leukemia treated with breakpoint cluster region-Abelson tyrosine kinase inhibitors are likely to survive in excess of 20 years after diagnosis. New challenges appear as we consider life after the disease, including professional challenges and the social reintegration of patients. The purpose of this study was to determine the impact of chronic myeloid leukemia on employment within 2 years after diagnosis. This prospective, observational study included patients diagnosed with chronic myeloid leukemia and treated with a tyrosine kinase inhibitor. Two populations were defined as patients who reported modifications in their professional activity during the study (Acti-Pro+) and patients who did not report a modification (Acti-Pro-). Cancer survivors received a self-assessment questionnaire. The primary endpoint was to determine the professional status of patients. One hundred patients completed the questionnaire. Sixty-six patients out of 100 reported professional activity within 2 years after their diagnosis. During the 2 years after the diagnosis, 65.2% (95% confidence interval (CI), 53.7-76.7) of patients faced modifications in their professional activity due to chronic myeloid leukemia or adverse effects of drug treatments (group Acti-Pro+); in contrast, 34.8% of patients did not report any impact on their occupational activity (group Acti-Pro-). Among modifications to work organization, a change in the number of working hours was the most represented. Other modifications comprised changes in status or work pace. A majority of chronic myeloid leukemia patients face professional consequences of their disease and treatments. Our findings suggest that adverse drug reactions are a major factor affecting the occurrence of work modifications in this context.

[Telehealth as state response strategy: systematic reviewLa telesalud como estrategia de respuesta del Estado: revisión sistemática]. / A telessaúde como estratégia de resposta do Estado: revisão sistemática.

OBJECTIVE: To identify telehealth initiatives described in the literature as a strategy for national health policies. METHOD: A systematic review was performed to identify articles focusing on the use of telehealth as a state response strategy to health problems or needs. The Virtual Health Library, PubMed, and Google Scholar were searched using the following keywords: "telessaude politicas", "implantacao telessaude", "telehealth policy", "telehealth America", "telehealth Asia", "telehealth Antartida", "telehealth Europe", "telehealth Africa", "telehealth Oceania". Data collection was performed from March 2016 to February 2017. RESULTS: Twenty-one articles describing telehealth initiatives in various countries, published in Portuguese, Spanish, and English, were analyzed. Concentration of studies on specific areas or regions was not detected. Most articles were published from 2014 to 2017. Telehealth initiatives have been used mainly to decrease health costs, for continued education of health care professionals, consultations between health care professionals, to strengthen primary health care, and to improve the access to health care in remote areas. CONCLUSIONS: Telehealth is used as state policy across the five continents, with variations in the degree of implementation. The main differences in telehealth among countries refer to infrastructure, financing, engagement of patients and caretakers, and position of the state regarding the role of telehealth.

OBJETIVO: Determinar las acciones de telesalud descritas en las publicaciones pertinentes como estrategia en materia de políticas nacionales de salud. MÉTODO: Se realizó un estudio de revisión sistemática de la producción científica sobre la utilización de la telesalud como estrategia de respuesta del Estado a los problemas o a las necesidades de salud de la población, en el cual se emplearon las bases de datos de la Biblioteca Virtual de Salud (BVS), PubMed y Google Académico. Los términos utilizados en la búsqueda fueron "telesalud política", "implantación telesalud", "telehealth policy", "telehealth America", "telehealth Asia", "telehealth Antarctica", "telehealth Europe", "telehealth Africa" y "telehealth Oceania". Los datos se recopilaron entre marzo del 2016 y febrero del 2017. RESULTADOS: Se analizaron 21 artículos en español, inglés y portugués sobre telesalud en distintos países. No hubo ninguna concentración importante de artículos por lugar ni región. El mayor número de publicaciones se registró entre el 2014 y el 2017. La estrategia de telesalud se ha puesto en práctica para reducir los costos de la atención de salud, fomentar la educación permanente de los profesionales de salud y facilitar las consultas entre ellos, fortalecer la atención primaria de salud y ampliar el acceso a los servicios de salud en las zonas remotas. CONCLUSIONES: La estrategia de telesalud se utiliza como política pública en África, América, Asia y Europa, pero existen variaciones con respecto a la fase de implantación. Las principales diferencias en materia de telesalud observadas en los distintos países correspondieron a infraestructura, financiamiento, compromiso de los enfermos y prestadores de cuidado, y postura del Estado frente al papel de la telesalud.

Comparison between pediatric and adult adipose mesenchymal stromal cells.

BACKGROUND: Adipose-derived mesenchymalstromal cells (ASC) are currently tested in regenerative medicine to promote tissue reconstruction after injury. Regardingautologous purpose, the possible loss of therapeutic function and cell properties during aging have been questioned in adults. To date no reliable information is available concerning ASC from pediatric patients and a better knowledge is required for clinical applications. METHODS: Subcutaneous adipose tissue was collected from 27 donors (0-1 years old) and 50 donors (1-12 years old) and compared with adult ASC for in vitro characteristics. ASC were then tested in a mouse model of limb ischemia. RESULTS: Cells from the stromal vascular fraction (SVF) and subsequent cultured ASC were prepared. Only a greater amount in SVF cell number and ASC proliferative rate were found. Cell phenotype, colony formingunit-fibroblast (CFU-F) content, immunomodulation effect and adipogenic, osteoblastic and angiogenic potentials were not significantly different. In vivo, pediatric ASC induced an increase in microangiographic score in a mouse model of limb ischemia, even though improvement in vascular density was not significantly correlated to limb rescue. Finally messengerRNA (mRNA) analysis using a microarray approach identified that only 305 genes were differentially expressed (217 down- and 88 up-regulated) in pediatric versus adult ASC, confirming that ASC from both age groups shared very close intrinsic properties. CONCLUSION: This is the first study reporting a comparative analysis of ASC from a large number of donors and showing that their in vitro and in vivo properties were similar and maintained during aging.

Aging-related decrease of human ASC angiogenic potential is reversed by hypoxia preconditioning through ROS production.

Adipose stroma/stem cells (ASC) represent an ideal source of autologous cells for cell-based therapy. Their transplantation enhances neovascularization after experimental ischemic injury. Aging is associated with a progressive decrease in the regenerative potential of mesenchymal stem cells (MSCs) from bone marrow. This work aims to determine the aging effect on human ASC capacities. First, we show that aging impairs angiogenic capacities of human ASC (hASC) in a mouse ischemic hindlimb model. Although no change in hASC number, phenotype, and proliferation was observed with aging, several mechanisms involved in the adverse effects of aging have been identified in vitro combining a concomitant decrease in (i) ASC ability to differentiate towards endothelial cells, (ii) secretion of proangiogenic and pro-survival factors, and (iii) oxidative stress. These effects were counteracted by a hypoxic preconditioning that improved in vivo angiogenic capacities of hASC from older donors, while hASC from young donors that have a strong ability to manage hypoxic stress were not. Finally, we identified reactive oxygen species (ROS) generation as a key signal of hypoxia on hASC angiogenic capacities. This study demonstrates for the first time that age of donor impaired angiogenic capacities of hASC in ischemic muscle and change in ROS generation by hypoxic preconditioning reverse the adverse effect of aging.

Endothelial and cardiac regeneration from adipose tissues.

For a long time, adipose tissue was only considered for its crucial role in energy balance and associated diseases. The discovery of the presence of immature cells highlights a putative role for these tissues as reservoirs of therapeutic cells. Indeed, since fat pads can be sampled by liposuction under local anesthesia in adult patients, adipose tissue represents a promising source of regenerative cells, particularly in cardiovascular regeneration. Indeed among other potentials, we and others have demonstrated the great angiogenic properties of adipose-derived stromal cells (ASCs) and the existence of peculiar cells, at least in mice, that are able to spontaneously give rise to functional cardiomyocytes. This review deciphers the different steps necessary to isolate, characterize, and manipulate such striking cells.

[Maltreatment: study from the perspective of the police department for the protection of the child and the adolescent in Salvador, Bahia]. / Maus-tratos: estudo através da perspectiva da delegacia de proteção à criança e ao adolescente em Salvador, Bahia.

This cross-sectional study describes the occurrences of maltreatment recorded over three years (1997-1999) in a Brazilian Police Department for the Protection of the Child and the Adolescent. Socio-demographic and physical data of victims, aggressors and denouncers were investigated in a sample consisting of 2073 cases. The victims were aged between 0-18 years, of which 56.1% were girls. Data were entered into EPI INFO 2000 software and analyzed using descriptive statistics and chi-square test to determine significant differences (p<0.05). All manifestations of abuse, except physical abuse, tend to occur more frequently in females, and tend to be more prevalent in the 11-to-15 year-old subgroup. Physical abuse was the most common offense (64.7%). Injuries of face and jaw were found in 65.3% of the cases. Most of the aggressors were males (71.8%). There was a positive correlation between gender (female) and sexual abuse. Physical violence against boys was more intensive, as indicated by the presence of more severe body lesions. Health professionals should increase their diagnostic skills and raise the awareness of their communities to take action for reducing the incidence and the impact of violence upon children and adolescents.

Chemotaxis and differentiation of human adipose tissue CD34+/CD31- progenitor cells: role of stromal derived factor-1 released by adipose tissue capillary endothelial cells.

The native CD34+/CD31- cell population present in the stroma-vascular fraction of human adipose tissue (hAT) displays progenitor cell properties since they exhibit adipocyte- and endothelial cell-like phenotypes under appropriate stimuli. To analyze the signals within hAT regulating their phenotypes, the influence of hAT-derived capillary endothelial cells (CECs) was studied on the chemotaxis and differentiation of the hAT-CD34+/CD31- cells. Conditioned medium from hAT-CECs led to a strong chemotaxis of the hAT-CD34+/CD31- cells that was inhibited with pretreatments with pertussis toxin, CXCR-4 antagonist, or neutralizing antibodies. Furthermore, hAT-CECs produced and secreted the CXCR-4 ligand, that is, the stromal derived factor-1 (SDF-1). Finally, hAT-CECs induced the differentiation of hAT-CD34+/CD31- cells toward an endothelial cell (EC) phenotype. Indeed, hAT-CECs and -CD34+/CD31- cell coculture stimulated in a two-dimensional system the expression of the EC CD31 marker by the hAT-progenitor cells and, in a three-dimensional approach, the formation of capillary-like structures via a SDF-1/CXCR-4 dependent pathway. Thus, the migration and differentiation of hAT progenitor cells are modulated by hAT-CEC-derived factors. SDF-1, which is secreted by hAT-derived CECs, and its receptor CXCR-4, expressed by hAT-derived progenitor cells, may promote chemotaxis and differentiation of hAT-derived progenitor cells and thus contribute to the formation of the vascular network during the development of hAT.

Inhibition of human preadipocyte proteasomal activity by HIV protease inhibitors or specific inhibitor lactacystin leads to a defect in adipogenesis, which involves matrix metalloproteinase-9.

In a previous publication, we reported that human immunodeficiency virus (HIV) protease inhibitors (PIs) inhibited the differentiation of human preadipocytes in primary culture, reducing the expression and secretion of matrix metalloproteinase 9 (MMP-9). The present work was performed to clarify this mechanism. Interestingly, HIV-PIs have been reported to be inhibitors of the proteasome complex, which is known to regulate nuclear factor (NF)-kappaB activation and transcription of its target genes, among them MMP-9. We thus investigated the potential involvement of the proteasome in the antiadipogenic effects of HIV-PIs. The effect of four HIV-PIs was tested on preadipocyte proteasomal activity, and chronic treatment with the specific proteasome inhibitor lactacystin was performed to evaluate alterations of adipogenesis and MMP-9 expression/secretion. Finally, modifications of the NF-kappaB pathway induced by either HIV-PIs or lactacystin were studied. We demonstrated that preadipocyte proteasomal activity was decreased by several HIV-PIs and that chronic treatment with lactacystin mimicked the effects of HIV-PIs by reducing adipogenesis and MMP-9 expression/secretion. Furthermore, we observed an intracellular accumulation of the NF-kappaB inhibitor, IkappaBbeta, with chronic treatment with HIV-PIs or lactacystin as well as a decrease in MMP-9 expression induced by acute tumor necrosis factor-alpha stimulation. These results indicate that inhibition of the proteasome by specific (lactacystin) or nonspecific (HIV-PIs) inhibitors leads to a reduction of human adipogenesis, and they therefore implicate deregulation of the NF-kappaB pathway and the related decrease of the key adipogenic factor, MMP-9. This study adds significantly to recent reports that have linked HIV-PI-related lipodystrophic syndrome with altered proteasome function, endoplasmic reticulum stress, and metabolic disorders.

Protease inhibitor treatments reveal specific involvement of matrix metalloproteinase-9 in human adipocyte differentiation.

We previously showed that human and murine 3T3-F442A preadipocytes produced and released matrix metalloproteinases (MMPs) 2 and 9 and that a treatment by MMP inhibitors resulted in the blockade of murine fat cell adipose conversion. In parallel, investigators reported that other protease inhibitors, the human immunodeficiency virus (HIV) protease inhibitors (PIs) involved in lipodystrophy in humans, also reduced the adipocyte differentiation process of several murine cell lines. The present work was performed to define the effects of MMP inhibitors and HIV-PIs on the human adipocyte differentiation process, to clarify the involvement of MMPs in the control of human adipogenesis, and to determine whether HIV-PIs interact with MMPs in the control of this process. The effect of two MMP inhibitor and four HIV-PI treatments on the differentiation of primary culture human preadipocytes, as well as the putative relationships between HIV-PIs and MMP-2 and -9 expression, release, or activity were investigated. We showed that MMP inhibitors and HIV-PIs reduced the human adipocyte differentiation process as assessed by the decrease of cell protein and/or triglyceride contents and expression of fatty acid binding protein and hormone-sensitive lipase, two adipocyte markers. Unlike MMP inhibitors, HIV-PIs were devoid of any effect per se on recombinant MMP-2 and 9 activities but reduced the expression and release of MMP-9 by human preadipocytes. Thus, the present study indicates that the modulation of the extracellular matrix components through the production and/or activity of MMPs, and, more precisely, MMP-9 might be a key factor in the regulation of human adipose tissue development.