Hyperuricemic PRP in tendon cells.

Platelet-rich plasma (PRP) is injected within tendons to stimulate healing. Metabolic alterations such as the metabolic syndrome, diabetes, or hyperuricemia could hinder the therapeutic effect of PRP. We hypothesise that tendon cells sense high levels of uric acid and this could modify their response to PRP. Tendon cells were treated with allogeneic PRPs for 96 hours. Hyperuricemic PRP did not hinder the proliferative actions of PRP. The gene expression pattern of inflammatory molecules in response to PRP showed absence of IL-1b and COX1 and modest expression of IL6, IL8, COX2, and TGF-b1. IL8 and IL6 proteins were secreted by tendon cells treated with PRP. The synthesis of IL6 and IL8 proteins induced by PRP is decreased significantly in the presence of hyperuricemia (P = 0.017 and P = 0.012, resp.). Concerning extracellular matrix, PRP-treated tendon cells displayed high type-1 collagen, moderate type-3 collagen, decorin, and hyaluronan synthase-2 expression and modest expression of scleraxis. Hyperuricemia modified the expression pattern of extracellular matrix proteins, upregulating COL1 (P = 0.036) and COMP (P = 0.012) and downregulating HAS2 (P = 0.012). Positive correlations between TGF-b1 and type-1 collagen (R = 0.905, P = 0.002) and aggrecan (R = 0.833, P = 0.010) and negative correlations between TGF-b1 and IL6 synthesis (R = -0.857, P = 0.007) and COX2 (R = -0.810, P = 0.015) were found.

Platelet-rich plasma in the conservative treatment of painful tendinopathy: a systematic review and meta-analysis of controlled studies.

BACKGROUND: Platelet-rich plasma (PRP) seeks to meet the multifaceted demand of degenerated tendons providing several molecules capable of boosting healing. AREAS TIMELY FOR DEVELOPING RESEARCH: PRP is used for managing tendinopathy, but its efficacy is controversial. SOURCES OF DATA: Electronic databases were searched for clinical studies assessing PRP efficacy. Methodological quality was evaluated using the methods described in the Cochrane Handbook for systematic reviews. AREAS OF AGREEMENT: Thirteen prospective controlled studies, comprising 886 patients and diverse tendons were included; 53.8% of studies used identical PRP protocol. AREAS OF CONTROVERSY: Sources of heterogeneity included different comparators, outcome scores, follow-up periods and diverse injection protocols, but not PRP formulation per se. GROWING POINTS: Pooling pain outcomes over time and across different tendons showed that L-PRP injections ameliorated pain in the intermediate-long term compared with control interventions, weighted mean difference (95% CI): 3 months, -0.61 (-0.97, -0.25); 1 year, -1.56 (-2.27, -0.83). However, these findings cannot be applied to the management of individual patients given low power and precision. RESEARCH: Further studies circumventing heterogeneity are needed to reach firm conclusions. Available evidence can help to overcome hurdles to future clinical research and bring forward PRP therapies.

Use of autologous platelet-rich clots for the prevention of local injury bleeding in patients with severe inherited mucocutaneous bleeding disorders.

Stopping or preventing local bleeding in patients with inherited bleeding disorders linked to abnormal platelet function is traditionally treated by transfusion of blood cell products or recombinant factor VIIa. We now report the use in such patients of autologous platelet-rich clots as an aid to preventing bleeding and to facilitating tissue regeneration at superficial sites. Two patients with von Willebrand's disease (VWD) type 2B and one patient with type I Glanzmann thrombasthenia were treated after tooth extraction and dental surgery. A fourth patient with platelet-type VWD underwent a skin biopsy. Whereas all four patients had a lifelong history of bleeding complications, the application of an autologous platelet-rich clot immediately after surgery combined with tranexamic acid intake to slow fibrinolysis prevented blood loss and resulted in rapid and normal healing. This new procedure is simple, safe and inexpensive; it provides extra security for patients with a bleeding risk undergoing dentistry or superficial surgery.

Fibroblastic response to treatment with different preparations rich in growth factors.

OBJECTIVES: Preparations rich in growth factors (PRGF) release them plus bioactive proteins at localized sites, with the aim of triggering healing and regenerative processes. The prevailing paradigm suggests that their influence on proliferation, angiogenesis and the extracellular matrix synthesis is minimal. However, variations in their composition and impact on different cell phenotypes have not been examined. MATERIALS AND METHODS: Sixteen fibroblast cultures obtained from three different anatomical sites (skin, synovium and tendon) of 16 donors were exposed to the molecular pool released from PRGF scaffolds, with increasing amounts of platelets. We evaluated cell proliferation, secretion of angiogenic growth factors (VEGF and HGF), synthesis of type I collagen and hyaluronic acid (HA), considering platelet dose and anatomical origin of the cells. Activity of transforming growth factor-beta (TGF-beta) in type I procollagen and HA synthesis was examined by adding exogenous TGF-beta to plasma preparations. RESULTS: All plasma preparations induced a significant proliferative response compared to non-stimulated cells (P < 0.05). Maximum proliferation rate was obtained with PRGF with 2-fold or 4-fold platelet concentration. Exposure to PRGF stimulated VEGF synthesis exclusively in tendon cells (P < 0.05), which also exhibited a different pattern of HGF production (P < 0.05). PRGF enhanced HA synthesis (P < 0.05), but did not alter collagen I production. Platelet-secreted TGF-beta may be involved in HA, but not in type I procollagen synthesis. CONCLUSIONS: Optimizing composition and use of platelet-rich products is crucial to enhancing the therapeutic potential of this technology. Our data show that the biological effects of PRGF may depend on concentration of platelets and on the anatomical source of the cells.

Intra-articular injection of an autologous preparation rich in growth factors for the treatment of knee OA: a retrospective cohort study.

OBJECTIVE: To obtain preliminary information about the effectiveness of intra-articular injections of an autologous preparation rich in growth factors (PRGF) for knee OA treatment to be explored further in future studies. METHODS: We have characterized PRGF treatment by platelet count and concentration of relevant growth factors (TGF-Beta1, PDGF-AB, VEGF-A; HGF and IGF-I) involved in healing mechanisms. We have performed an observational retrospective cohort study using hyaluronan injections as a control. Each group included 30 patients with OA of the knee, matched according to age, sex, body mass index and radiographic severity. Both treatments were based on three weekly injections. Clinical outcome was examined using the WOMAC questionnaires prior to treatment and at 5 weeks after treatment. RESULTS: The observed success rates by week 5 for the pain subscale reached 33.4% for the PRGF group and 10% for the hyaluronan group. The difference was attributed exclusively to the treatment modality, p = 0.004. The percent reductions in the physical function subscale and overall WOMAC at 5 weeks were also associated solely with treatment modality in favour of PRGF, p = 0.043 and p = 0.010 respectively. CONCLUSIONS: Although these preliminary results need to be evaluated in a randomized clinical trial, they provide useful infomration about the safety of PRGF and open new perspectives on autologous treatments for joint diseases.

The relationship between HAART use and sexual activity among HIV-positive women of reproductive age in Brazil, South Africa, and Uganda.

The purpose of this study was to determine whether current HAART use is associated with recent sexual intercourse among HIV-infected women (18-49 years) from Brazil, South Africa and Uganda. We conducted an analysis of survey data from a cross-sectional study, which enrolled 179 HIV-infected women receiving regular care from the Mbarara Hospital HIV Clinic in Uganda (n=85); the Perinatal HIV Research Unit in Soweto, South Africa (n=50); and the IPEC-Fiocruz cohort in Rio de Janeiro, Brazil (n=44). The primary outcome was sexual intercourse in the previous month. Secondary outcomes were protected sex and contraceptive use. We found that overall, 46% reported recent sexual intercourse. After adjusting for covariates, recent sexual intercourse was not associated with HAART use (AOR: 0.76; 95%CI: 0.34-1.72); however, it was significantly associated with being currently married, wanting to have more children and having higher HAART optimism. Among women reporting recent sexual intercourse (n=83), HAART users were significantly more likely to practice protected sex (crude OR: 3.64; 95%CI: 1.41-9.38) and non-significantly more likely to use contraceptive methods (crude OR: 2.15; 95%CI: 0.77-5.99). In summary, self-reported recent sexual intercourse is not more likely among women on HAART. Moreover, sexually active HAART users may be more likely to practice protected sex and use contraceptives.

Echocardiographic features of cardiac failure in Uganda.

Cardiac failure is a common medical presentation in Uganda. This study primarily focuses on the aetiology of heart failure in 65 adult patients and assesses the utility of echocardiography in a resource-limited setting. Our findings suggest that endomyocardial fibrosis is much less prevalent than previously described in other regions of Uganda and highlights the need for more basic descriptive studies on common presenting illnesses in rural Africa.

Platelet-released growth factors enhance the secretion of hyaluronic acid and induce hepatocyte growth factor production by synovial fibroblasts from arthritic patients.

OBJECTIVES: Autologous platelet-secreted growth factors (GFs) may have therapeutic effects in osteoarthritis (OA) capsular joints via multiple mechanisms. Our aim was to examine the effect of a platelet-derived preparation rich in growth factors (PRGFs) in OA synovial cell biology. METHODS: Synovial cells were isolated from 10 osteoarthritic patients and cultured in serum-free media (basal conditions) and exposed to either a platelet-poor preparation or PRGF for 72 h. Cells activated with interleukin-1beta (IL-1beta) for 48 h were also exposed to PRGF. Changes in several events relevant to joint homeostasis including (i) hyaluronic acid (HA) secretion, (ii) the balance between metalloproteinase-1, -3 and -13 (MMP-1, MMP-3 and MMP-13) and tissue inhibitor-1 (TIMP-1) and (iii) the secretion of transforming growth factor-beta1(TGF-beta1), vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF), were all assessed. RESULTS: PRGF significantly enhanced HA secretion compared with platelet-poor preparations, P < 0.05; at the same time release of TIMP-1, MMP-1, MMP-3 and MMP-13 were not affected. An increased HGF production was observed (P < 0.05) but VEGF and TGF-beta1 levels remained unchanged. PRGF significantly enhanced the secretion of HA induced by IL-1beta activation, P < 0.05, but it did not modify the IL-1beta-induced rise in MMP-1, MMP-3 and VEGF. In contrast, PRGF-induced HGF production was abolished by the presence of IL-1beta during PRGF treatment, P < 0.05. CONCLUSIONS: Intra-articular administration of PRGF might be beneficial in restoring HA concentration and switching angiogenesis to a more balanced status but does not halt the effects of IL-1beta on synovial cells.

[Face recognition in autism]. / Reconocimiento de caras en autismo.

INTRODUCTION: We conducted a survey of the literature on face recognition (FR), an activity that is essential for social relations and their dynamics. Unlike the recognition of non facial objects, this type of recognition is a special process since it is based on the detection of individual features. The most characteristic clinical parameter of autistic subjects is their inability to relate socially, possibly due to the difficulty they have in processing faces, although they are more skilled at recognising objects. DEVELOPMENT: We describe the two mechanisms involved in FR, one based on features and the other referring to the whole. The latter can be further divided into overall processing that allows a whole image to be compared with another previously assimilated image, and the processing of the arrangement of a face that is recognised as a whole. These may correspond to two different neuronal pathways. During the first days of life, the newborn baby has a predilection for faces in their feature and overall aspects, and processing of the arrangement is slower. Visual development in autistic children is erratic, similar to the level of a newborn infant, and their lack of interest for human faces is apparent during the first year of life, as they look at everything as if they were objects, that is, by features. CONCLUSIONS: The analysis of the literature enabled us to determine how FR mechanisms develop in the earliest days of the infant s life. It also highlighted the importance of the integrity of the pathway that facilitates stimulation for the recognition of facial arrangement, which is altered in autistic children perhaps from the peripheral area to the cortex. Further work on peripheral pathways and the fundamental cortical connections that are affected in autistic subjects will help us to understand the inefficiency of their facial arrangement recognition system.

Reconocimiento de caras en el autismo / Face recognition in autism

Introducción. Se realiza una revisión bibliográfica sobre el reconocimiento de caras (RDC), actividad fundamental para las relaciones sociales y su dinámica. Este tipo de reconocimiento es un proceso especial, en contraste con el reconocimiento de objetos no faciales, pues se basa en la detección de características individuales. El parámetro clínico más característico de los autistas es su imposibilidad para la relación social, posiblemente por su dificultad para el procesamiento de caras, aunque poseen una mayor habilidad en el reconocimiento de objetos. Desarrollo. Se plantean los dos mecanismos en el RDC, el de los rasgos y el de conjunto. El segundo comprende el procesamiento global, que permite comparar la totalidad de la imagen con una imagen previamente asimilada, y el procesamiento de la configuración de la cara reconocida como un todo; ambos pueden corresponder a dos redes neuronales distintas. En los primeros días de vida, el recién nacido tiene preferencia por las caras en sus aspectos de rasgos y global, y es más lento el proceso de la configuración. El desarrollo visual en los niños autistas es errático, como si fuese el nivel de un recién nacido, y su desinterés por las caras humanas es evidente en el primer año de vida, al mirar todo como objetos, por rasgos. Conclusiones. El análisis de la bibliografía ha permitido plantear cómo se desarrollan los mecanismos de lRDC desde los primeros días de vida, y la importancia que desempeña la integridad de la vía que facilita la estimulación para el reconocimiento de la configuración facial, alterada en los niños autistas, posiblemente desde la periferia al córtex. Nuevos trabajos sobre las vías periféricas y las conexiones corticales fundamentales afectadas en autistas ayudarán a comprender la ineficiencia de su sistema de reconocimiento de la configuración facial (AU)

Differential effect of haloperidol and clozapine on plasma homovanillic acid in elderly schizophrenic patients with or without tardive dyskinesia.

BACKGROUND: Plasma homovanillic acid (HVA) changes in response to a challenge of several days with haloperidol have been found to be predictive of the therapeutic response to haloperidol over a longer period of treatment. METHODS: Twenty-six elderly women who gave informed consent were divided into two groups, with or without tardive dyskinesia, and subjected to an 80-day washout, after which both the dyskinetic and nondyskinetic group was divided, and half of each group given haloperidol or clozapine. CONCLUSIONS: The nondyskinetic group had a brief rise in plasma HVA, then a decline. The dyskinetic group had no change in plasma HVA. Neither group challenged with clozapine had any change in plasma HVA.

Schizophrenia: gender, family risk, and plasma homovanillic acid.

Plasma homovanillic acid concentration was assessed in 60 young schizophrenic patients, with and without first-degree relatives with schizophrenia, before treatment, and 3 days after starting haloperidol treatment. The baseline concentration of homovanillic acid in plasma was no different in the two groups before treatment; it was, however, significantly higher in the patients with relatives than in those without relatives diagnosed of schizophrenia after 3 days of haloperidol treatment.

Chronic neuroleptic treatment does not suppress the dynamic characteristics of the dopaminergic receptor D2 system.

1. Rats were treated with either haloperidol (0.5 mg/kg) or haloperidol plus an anticholinergic drug (0.5 and 0.15 mg/kg/day respectively) for 3 days, 7 days and 16 months. 2. Estimates made twenty hours after the last doses showed that haloperidol reduced the concentrations of the dopamine metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the striatum and the olfactory tubercle. 3. A challenge dose of either haloperidol or haloperidol plus an anticholinergic drug was administered to rats pretreated with haloperidol or haloperidol plus an anticholinergic drug; this challenge dose reversed the reduction in dopamine metabolites caused by neuroleptic administration. 4. After sixteen months of haloperidol administration dopamine levels were reduced, but adding an anticholinergic drug to haloperidol treatment prevented this reduction in dopamine concentration.

Morning variations of plasma homovanillic acid in untreated schizophrenic patients.

Plasma concentrations of homovanillic acid were determined in samples obtained at 8.30 a.m. and 12.30 p.m. from 29 untreated schizophrenic patients, 14 males and 15 females. When the earlier samples were compared with the later, a significant decrease in mean plasma homovanillic acid level was observed, but only in the male patients. The morning fall was observed in 10 of 14 male patients and 6 of the 15 female patients. This morning rhythm in plasma homovanillic acid concentration may mask the putative rises in plasma homovanillic acid provoked by neuroleptic administration and may explain some of the observed differences between findings in studies involving the assessment of this metabolite.

Evidence of low dopaminergic activity in elderly women with spontaneous orofacial dyskinesia.

Evidence of low dopaminergic activity was found in elderly women exhibiting spontaneous orofacial dyskinesias. The dyskinesia was significantly reduced by haloperidol. The results are not compatible with dopamine receptor supersensitivity in this dyskinesia.

Persistence of cyclicity of the plasma dopamine metabolite, homovanillic acid, in neuroleptic treated schizophrenic patients.

The dopamine metabolite, homovanillic acid, decreases in concentration in plasma between 8:30 A.M. and 12:30 P.M. In patients with schizophrenia this cyclic change is attenuated by chronic neuroleptic treatment; however, if the 8 A.M. dose of neuroleptic is omitted, the decrease in level occurs. Presuming that neuroleptics attenuate the decline through a receptor mediated compensatory increase in dopamine release, it would appear that receptors are not fully occupied by neuroleptics even at therapeutically effective doses. The usual morning decrease in plasma cortisol levels was unaffected by neuroleptics.

Plasma homovanillic acid as a predictor of response to neuroleptics.

Fourteen schizophrenic subjects were evaluated for degree of psychosis before and after treatment with the antipsychotic drug haloperidol and for plasma homovanillic acid concentration after four and 28 days of treatment. A significant correlation was found between an increase in homovanillic acid concentration on day 4 or a decrease from day 4 to day 28 and the degree of improvement after four weeks of treatment. Thus, those patients who had the greatest change in plasma homovanillic acid in response to neuroleptic blockade showed the greatest improvement. These and other observations have led us to propose that the central dopaminergic system, through adaptive changes in activity, serves as a physiologic buffer system protecting against destabilization of mental function from diverse biologic or psychologic insults.