RESUMO
We showed that the chemokine receptor C-X-C Motif Chemokine Receptor 2 (CXCR2) is essential for cartilage homeostasis. Here, we reveal that the CXCR2 ligand granulocyte chemotactic protein 2 (GCP-2) was expressed, during embryonic development, within the prospective permanent articular cartilage, but not in the epiphyseal cartilage destined to be replaced by bone. GCP-2 expression was retained in adult articular cartilage. GCP-2 loss-of-function inhibited extracellular matrix production. GCP-2 treatment promoted chondrogenesis in vitro and in human cartilage organoids implanted in nude mice in vivo. To exploit the chondrogenic activity of GCP-2, we disrupted its chemotactic activity, by mutagenizing a glycosaminoglycan binding sequence, which we hypothesized to be required for the formation of a GCP-2 haptotactic gradient on endothelia. This mutated version (GCP-2-T) had reduced capacity to induce transendothelial migration in vitro and in vivo, without affecting downstream receptor signaling through AKT, and chondrogenic activity. Intra-articular adenoviral overexpression of GCP-2-T, but not wild-type GCP-2, reduced pain and cartilage loss in instability-induced osteoarthritis in mice. We suggest that GCP-2-T may be used for disease modification in osteoarthritis.
Assuntos
Quimiocina CXCL6 , Osteoartrite , Humanos , Animais , Camundongos , Quimiocinas CXC/metabolismo , Quimiocinas CXC/farmacologia , Camundongos Nus , Estudos Prospectivos , Receptores de Quimiocinas , CondrogêneseRESUMO
Background: Leptin is a hormone regulating lifetime energy homeostasis and metabolism and its concentration is important starting from prenatal life. We aimed to investigate the association of perinatal leptin concentrations with growth trajectories during the first year of life. Methods: Prospective, longitudinal study, measuring leptin concentration in maternal plasma before delivery, cord blood (CB), and mature breast milk and correlating their impact on neonate's bodyweight from birth to 1 year of age, in 16 full-term (FT), 16 preterm (PT), and 13 intrauterine growth-restricted (IUGR) neonates. Results: Maternal leptin concentrations were highest in the PT group, followed by IUGR and FT, with no statistical differences among groups (p = 0.213). CB leptin concentrations were significantly higher in FT compared with PT and IUGR neonates (PT vs. FT; IUGR vs. FT: p < 0.001). Maternal milk leptin concentrations were low, with no difference among groups. Maternal leptin and milk concentrations were negatively associated with all the neonates' weight changes (p = 0.017 and p = 0.006), while the association with CB leptin was not significant (p = 0.051). Considering each subgroup individually, statistical analysis confirmed the previous results in PT and IUGR infants, with the highest value in the PT subgroup. In addition, this group's results negatively correlated with CB leptin (p = 0.026) and showed the largest % weight increase. Conclusions: Leptin might play a role in neonatal growth trajectories, characterized by an inverse correlation with maternal plasma and milk. PT infants showed the highest correlation with hormone levels, regardless of source, seeming the most affected group by leptin guidance. Low leptin levels appeared to contribute to critical neonates' ability to recover a correct body weight at 1 year. An eventual non-physiological "catch-up growth" should be monitored, and leptin perinatal levels may be an indicative tool. Further investigations are needed to strengthen the results.
Assuntos
Trajetória do Peso do Corpo , Leptina , Peso ao Nascer , Feminino , Retardo do Crescimento Fetal , Humanos , Lactente , Recém-Nascido , Estudos Longitudinais , Gravidez , Estudos ProspectivosRESUMO
Endometriosis is a chronic gynecological disorder involved in the pathogenesis of chronic pelvic pain, based on a probable up regulation of the inflammatory system. The objective of the study is to investigate the peritoneal and serum levels of ENA-78 with the severity of endometriosis symptoms (dysmenorrhea, chronic pelvic pain and dyspareunia) using the visual analogue scale (VAS). This is a prospective case-control study that included 53 symptomatic women with evidence of endometriosis and 53 age-matched controls who underwent elective laparoscopic surgery for benign diseases. The concentration of ENA-78 was assessed in blood and peritoneal fluid samples in the follicular phase. In peritoneal fluid and plasma, the concentration of ENA-78 was significantly higher in cases than in controls (p < 0.001). A significant correlation was observed between peritoneal fluid ENA-78 levels and the severity of dysmenorrhea (Spearman Rho = 0.237; p = 0.014), and chronic pelvic pain (Spearman Rho = 0.220; p = 0.022) in endometriosis patients. Plasma levels ENA-78 showed a significant correlation with the severity (VAS score) of chronic pelvic pain (Spearman Rho = 0.270, p = 0.005 for cases), though a weak correlation was evident between plasma levels of ENA-78 and severity of dysmenorrhea (Spearman Rho = 0.083, p = 0.399 for cases). In conclusion, chronic pelvic pain in endometriosis is caused by changes of local and systemic activated chemokine patterns. These modifications involve the relationship between pro-inflammatory, angiogenic and angiostatic chemokines that modulate the severity of endometriosis associated symptoms.
Assuntos
Dor Crônica , Endometriose , Laparoscopia , Estudos de Casos e Controles , Doença Crônica , Dor Crônica/complicações , Dismenorreia/etiologia , Endometriose/patologia , Feminino , Humanos , Neutrófilos/patologia , Dor PélvicaRESUMO
OBJECTIVE: To evaluate the dynamical interplay between perinatal leptin concentrations and neonatal weight evolution until 3 months of age. METHODS: In a prospective observational study, maternal, cord blood and neonatal plasma leptin concentrations were correlated to birthweight and 3-month weight in 26 full-term, 20 preterm, and 17 intrauterine growth restriction (IUGR) mother-neonate couples. RESULTS: The median of maternal, cord blood, neonatal leptin concentrations were significantly different among the three groups (p = 0.010; <0.001; =0.041 correspondingly). In the respect of the full-term group, higher concentrations were reported in preterm and IUGR mothers and lower concentrations in cord blood and neonatal plasma. The post-hoc comparisons showed that maternal concentrations were significantly higher in the IUGR group (p = 0.005 vs full-term), cord blood concentrations resulted always significantly lower (preterm, IUGR vs full-term p < 0.001) and neonatal concentrations were significantly lower in the preterm group (p = 0.018 vs full-term). Neonatal birthweight and 3-month weight were always significantly different among groups (p < 0.001), even if preterm and IUGR still had lower weight than full-term, the percent increasing of weight between birth and 3-month demonstrated that preterm and IUGR infants have grown significantly faster, (preterm, IUGR vs full-term p < 0.001). The univariable analysis showed a maternal leptin association with offspring' birthweight (R = -38%, p = 0.006) and with 3-month weight (R = -43%, p = 0.002). Accounting for confounders, these associations lost significance. Cord blood leptin concentrations positively correlated with birthweight and with 3-month weight (both, p < 0.001). The latter correlation, when adjusting for birthweight became negative (R = -43% p < 0.001). CONCLUSION: Our results showed that maternal leptin levels lost their influence on neonatal weight when considering confounders. At 3-month, once birthweight adjusted, the percent increasing of weight was statistically larger in preterm and IUGR than the full-term group and the correlation between cord blood leptin and weight turned negative, from positive at birth. These data may be a clue for further investigation on the relationship between perinatal leptin concentrations and catch-up growth.
Assuntos
Retardo do Crescimento Fetal , Leptina , Peso ao Nascer , Feminino , Idade Gestacional , Humanos , Lactente , Recém-Nascido , Mães , GravidezRESUMO
The purpose of the study was to compare cytokines (CK) and chemokines concentrations in blood and cervico-vaginal samples between human papillomavirus (HPV)-positive and HPV-negative women, who had no previous history of HPV infection. A case-control study compares the activity and the concentration of CK/chemokines between 19 HPV-positive and 22 HPV-negative women matched by age. Plasma and cervico-vaginal levels of CK and chemokines were measured using cytofluorimetric analysis and expressed as mean of percentages. Plasma rates of interleukin (IL)-6 were significantly greater in HPV-negative women (mean value of 5.20±4.79 pg/ml) in comparison with HPV-positive women (mean value of 2.57±3.09 pg/ml) (p = 0.001). On the contrary, plasma levels of Eotaxin and hMCP-1 were significantly higher in HPV-positive women, with a mean value of 13.87±4.54 pg/ml (p = 0.022) and 53.53±19.51 pg/ml (p = 0.005), respectively. Differences in cervico-vaginal CK/chemokines concentrations were statistically not significant. Difference in plasma concentrations of IL-6, Eotaxin, IL-1ß and hMCP-1 was statistically significant even by analyzing HPV-16/18 and multiple HPV genotypes infections. Primary HPV infection shows a characteristic pattern of plasma CK/chemokines concentration as opposed to HPV-negative subjects and persistent HPV infection. Keywords: chemokines; cytokines; HPV primary infection; plasma pattern.
Assuntos
Infecções por Papillomavirus , Estudos de Casos e Controles , Quimiocinas , Citocinas , Feminino , Papillomavirus Humano 16/genética , Papillomavirus Humano 18 , Humanos , Projetos PilotoRESUMO
BACKGROUND: Type I endometrial cancer is the most common gynaecological tumour in developed countries and its incidence is increasing also because of population aging. The aim of this work is to test the feasibility and safety of anastrozole as palliative treatment of endometrial cancer in elderly women ineligible for standard surgical treatment. METHODS: Patients with histological diagnosis of type I endometrial cancer not suitable for surgical treatment were enrolled in this pilot study. Anastrozole was administered 1 mg daily orally after performing an accurate clinical and radiological staging. Validated questionnaire and self-reported outcomes were used to evaluate quality of life and compliance during the study period. RESULTS: Eight patients with a mean age of 85 (range 80-88 years) were enrolled. All patients had endometrial cancer confined to the uterus, and none progression of disease was observed during the study period. A partial response to the therapy was reported in seven patients, while one patient had stable disease. Tumour symptoms improvement such as pain, vaginal bleeding and vaginal discomfort was reported. The endometrial thickness after twelve months has showed a reduction of 9.25 ± 4.77 mm. The average follow-up time was 18.25 months. Four women died for non oncological reasons, none death related to endometrial cancer was reported. Evaluation of symptoms showed a significant reduction of appetite loss and insomnia, while a significant increase of global health status and fatigue was reported. CONCLUSIONS: Our preliminary data suggested that the palliative use of anastrozole may be a suitable therapy for the proper management of early stages endometrial cancer in elderly women not suitable for surgical treatment with good compliance and tolerance. TRIAL REGISTRATION: 2013000840. Date of registration: 21/09/2013. URL: trials.sanmatteo.loc .
Assuntos
Neoplasias do Endométrio , Qualidade de Vida , Idoso , Idoso de 80 Anos ou mais , Anastrozol/uso terapêutico , Neoplasias do Endométrio/tratamento farmacológico , Feminino , Humanos , Nitrilas/uso terapêutico , Cuidados Paliativos , Projetos Piloto , Tamoxifeno , Triazóis/uso terapêuticoRESUMO
BACKGROUND: Measuring service quality aids health care providers to recognize specific and unmet needs of patients. Nevertheless, perceived quality of health care services (PQC) is often investigated with inadequate techniques which may lead to biased results. OBJECTIVE: The aim of the present study is to develop a proof-of-concept for estimating the PQC using the scale-up estimator, with reference to a concrete assessment in patients of a major Oncology Hospital in Veneto (IOV). Results have then been compared with those collected by the Customer Relations Office (CRO) after the annual survey conducted with traditional questionnaire based techniques. MATERIAL AND METHODS: Seven hundred and eighty-three sets consisting of two questionnaires were handed out to IOV patients between 26 and 28 November 2012. The first questionnaire was the CRO annual one composed by 15 direct questions about the perception of quality satisfaction rate using a Likert scale. The second questionnaire was the scale-up (NSUM) one, composed by 20 indirect questions, 5 of which were reproducing the main target of CRO for estimating PQC. RESULTS: The comparisons made over 299 sets of questionnaires showed differences between the two techniques. Network Scale-Up Method (NSUM) questionnaire seems to be able to produce lower estimates of PQC with respect to the CRO annual questionnaire. In some cases, the NSUM showed dissatisfaction rates which are 20-fold higher respect to CRO. CONCLUSION: NSUM could be a promising method for assessing the perceived quality of care.