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Background: Invasive Meningococcal Disease is a severe disease mainly affecting infants and young children. Most infections are caused by serogroups A, B, C, W, X, and Y. In the last 10 years, serogroup B has been the main cause of Invasive Meningococcal Disease in Europe. Recent data resulting from an observational study conducted in Italy show a significant reduction in the number of Invasive Meningococcal Disease cases due to Neisseria meningitidis B after the introduction of vaccine 4CMenB. Thus, the Naples Team of Federation of Italian Primary Care Pediatricians and the Public Health Department started an active collaboration focused on vaccination process management (named "Progetto Via") with the aim of increasing Meningococcal B vaccination coverage. Study design: Source of data is the regional platform "GE.VA.". Every Primary care Pediatrician uses daily to record vaccination activity. This platform is integrated with data entered by operators of the District/Vaccination Center. Methods: Time: January 2019 - December 2019. The Federation of Italian Primary Care Pediatricians/Naples organized a meeting to identify six coordinators. The pediatricians could choose to counsel in their own offices and send children to the vaccination center or to counsel and vaccinate directly in their own clinics. Results: A total of 78 pediatricians took part in the project: 46 did only counseling and 32 did both counseling and vaccination in their medical clinic. Data obtained show an overall average vaccination coverage growth of about 13% in the first 4 months of the survey, and a further growth of about 11% in the following seven months, with a total growth in the entire period of 24%. The pediatricians' counseling is essential to recover non-compliant subjects, considering both the relationship of trust with the families and the visits already scheduled as an ideal moment for vaccinations' status check. Conclusions: The project highlights how an effective collaboration between family pediatricians and the Local Health Authority becomes valuable in getting closer to reach the Ministerial goal of 95%. Vaccination coverage increased significantly when family pediatricians supported the activity of vaccine centers in distress in many regional situations. The trust relationship, the hourly availability and the capillary network of family pediatricians' clinics were key elements for the success of this project and were also recognized by parents.
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Infecções Meningocócicas , Vacinas Meningocócicas , Criança , Pré-Escolar , Humanos , Lactente , Itália , Infecções Meningocócicas/prevenção & controle , Pediatras , Saúde Pública , Vacinação , Cobertura VacinalRESUMO
Proinflammatory cytokines and heat shock proteins play relevant roles in the pathogenesis of inflammatory diseases. We investigated whether Hsp70 1267 A/G and TNF-α -308 G/A polymorphisms are associated with proinflammatory mediators, zinc status and laboratory parameters in 1,078 healthy elderly from ZincAge study. Hsp70 1267 A/G genotype and allele distribution were similar among various European countries, while a TNF-α genetic heterogeneity was observed between the Northern and the Southern European populations, with a major frequency of the -308 A variant in France, Germany and Poland. We used linear regression models to test additive, dominant or recessive associations of each SNP with proinflammatory mediators, laboratory parameters, metallothioneins and zinc status. Hsp70 1267 A/G SNP, but not TNF-α -308 G/A SNP, influences TNF-α and IL-6 plasma levels under additive, dominant and recessive models (for TNF-α only). An association between Hsp70 1267 A/G SNP and zinc plasma levels was observed in the dominant model. In particular, G allele carriers showed increased circulating pro-inflammatory cytokines and zinc. Moreover, both these SNPs affect creatinine levels suggesting a possible influence on renal function. In conclusion, Hsp70 1267 A/G SNP is associated with pro-inflammatory cytokine production in healthy elderly and might represent a possible determinant of individual susceptibility to inflammatory diseases.
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Envelhecimento/metabolismo , Citocinas/sangue , Proteínas de Choque Térmico HSP70/genética , Inflamação/sangue , Polimorfismo de Nucleotídeo Único/genética , Fator de Necrose Tumoral alfa/genética , Zinco/metabolismo , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/genética , Proteína C-Reativa/metabolismo , Europa (Continente) , Feminino , Frequência do Gene/genética , Genótipo , Homeostase/fisiologia , Humanos , Inflamação/genética , Masculino , Metalotioneína/metabolismo , Pessoa de Meia-IdadeRESUMO
AIMS: ZnT8 Arg325Trp polymorphism has been associated with type 2 diabetes (T2DM) susceptibility. The Arg-325 risk variant shows accelerated zinc (Zn) transport kinetic and reduced glucose-stimulated insulin secretion in pancreatic cells. However, it remains unexplored the role of Znt8 polymorphism in the regulation of Zn homeostasis and inflammatory response in peripheral blood mononuclear cells (PBMCs) from T2DM patients. METHODS AND RESULTS: A total of 556 healthy controls and 413 T2DM patients were genotyped for ZnT8 Arg325Trp polymorphism confirming the association of Arg-325 variant with an increased T2DM risk (ORâ¯=â¯1.35 95% C.I: 1.10-1.66; pâ¯=â¯0.0044). Moreover, PBMCs from Arg/Arg T2DM subjects showed increased intracellular free Zn, higher gene expression of Metallothioneins, Znt1, Znt8, Zip2 genes, and reduced Znt4 and Znt7. Higher release of IL-1α, IL-1ß, IFN-γ, IL-12p70 and TNF-α and a reduced IL-10 secretion after lipopolysaccharide (LPS) stimulation were observed in PBMCs from Arg/Arg T2DM carriers as compared to subjects with the Trp variant. CONCLUSIONS: Our data provide evidence of a substantial different Zn homeostasis regulation between Znt8 Arg-325 and Trp-325 carriers in PBMCs from T2DM patients. Moreover, Znt8 Arg-325 risk variant shows an enhanced inflammatory response upon LPS stimulation that might aggravate insulin resistance and the progression of diabetes cardiovascular complications.
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Proteínas de Transporte/metabolismo , Citocinas/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Leucócitos Mononucleares/metabolismo , Polimorfismo Genético , Transportador 8 de Zinco/genética , Zinco/metabolismo , Idoso , Idoso de 80 Anos ou mais , Proteínas de Transporte/genética , Estudos de Casos e Controles , Proteínas de Transporte de Cátions/genética , Proteínas de Transporte de Cátions/metabolismo , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/patologia , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Optimization of the energy levels at the donor-acceptor interface of organic solar cells has driven their efficiencies to above 10%. However, further improvements towards efficiencies comparable with inorganic solar cells remain challenging because of high recombination losses, which empirically limit the open-circuit voltage (Voc) to typically less than 1 V. Here we show that this empirical limit can be overcome using non-fullerene acceptors blended with the low band gap polymer PffBT4T-2DT leading to efficiencies approaching 10% (9.95%). We achieve Voc up to 1.12 V, which corresponds to a loss of only Eg/q - Voc = 0.5 ± 0.01 V between the optical bandgap Eg of the polymer and Voc. This high Voc is shown to be associated with the achievement of remarkably low non-geminate and non-radiative recombination losses in these devices. Suppression of non-radiative recombination implies high external electroluminescence quantum efficiencies which are orders of magnitude higher than those of equivalent devices employing fullerene acceptors. Using the balance between reduced recombination losses and good photocurrent generation efficiencies achieved experimentally as a baseline for simulations of the efficiency potential of organic solar cells, we estimate that efficiencies of up to 20% are achievable if band gaps and fill factors are further optimized.
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OBJECTIVE: To evaluate growth and pubertal development in children with IDDM and the influence of the age at onset of IDDM and the degree of metabolic control on final height. RESEARCH DESIGN AND METHODS: We conducted a retrospective evaluation of 62 subjects followed longitudinally both clinically and metabolically from the onset of IDDM until final height was reached. RESULTS: Height at diagnosis was within the normal percentiles in boys (0.5 +/- 1.0 standard deviation score [SDS]) and girls (0.4 +/- 1.0 SDS), but above the genetic target height (-1.0 +/- 0.9 SDS in boys and -1.1 +/- 0.6 SDS in girls; P = 0.0001 for both comparisons). Although a lesser height gain was observed during the ensuing years, the final height reached by boys (-0.4 +/- 1.1 SDS) and girls (-0.4 +/- 0.9 SDS) was higher than the genetic target height. Blunted total pubertal growth was observed both in boys (24.5 +/- 3.6 cm) and girls (20.1 +/- 4.2 cm). The decrease in height gain was independent of the duration of IDDM, the degree of metabolic control, or the insulin requirement. The greater the height at diagnosis, with respect to the genetic target height, the lesser was the subsequent height gain to reach final adult height (r = 0.34, p < 0.01). BMI increased with age as normally occurs in healthy children, independent of the duration of disease and the degree of metabolic control. Pubertal development began and progressed normally both in boys and girls. In boys, a testicular volume of 4 ml was reached at a mean age of 12.1 +/- 0.9 years. In girls, breast enlargement occurred at a mean age of 10.4 +/- 1.2 years and the mean age of menarche was 12.8 +/- 1.4 years. Pubertal development and progression occurred independent of the age at onset of IDDM, the glycemic control, or the insulin requirement during the pubertal period. CONCLUSIONS: Children with IDDM have normal onset of puberty and normal sexual maturation. Even though final height falls within the normal percentiles, the diminished height gain after diagnosis requires further investigation.
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Glicemia/metabolismo , Estatura , Diabetes Mellitus Tipo 1/fisiopatologia , Crescimento , Puberdade , Maturidade Sexual , Adulto , Idade de Início , Criança , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/tratamento farmacológico , Feminino , Hemoglobinas Glicadas/análise , Humanos , Insulina/uso terapêutico , Estudos Longitudinais , Masculino , Menarca , Análise de Regressão , Estudos Retrospectivos , Fatores SexuaisRESUMO
Different age-related immune pathogenetic mechanisms in myasthenia gravis (MG) have been suggested because of restoration after thymectomy (Tx) of altered zinc, thymulin (TH) and T-cell subsets exclusively in early-onset patients (younger <50 years), not in late-onset patients (older >50 years). In this context interleukin-2 (IL-2), interleukin-6 (IL-6) and thymoma are crucial because both involved in MG pathogenesis and correlated with acetylcholine receptors (AchRs) Ab production. Moreover, IL-2 and IL-6 are zinc-dependent, are altered in aging and related with zinc and TH age-dependent declines. Moreover, zinc is relevant for immune efficiency. In order to confirm these different age-related pathogenetic mechanisms further, the role of thymoma, zinc, TH, IL-2 and IL-6 is studied in MG patients with generalized MG with and without thymoma before and 1 month and 1 year after Tx. The high IL-2, IL-6, zinc, and AChR Ab levels observed before Tx are significantly correlated each other in younger MG patients (<50 years) independently by thymoma and in older MG patients (>50 years) with thymoma. No correlations exist in older MG patients without thymoma. Thymulin is not correlated with other parameters considered to be both in younger and older MG patients independently by the thymoma. Thymectomy restores zinc; immune parameters and AChR Ab are exclusively in the younger group, not in the older one. These findings suggest that IL-2 and IL-6, via zinc, rather than TH, may be involved in different age-related pathogenetic mechanisms mainly in early-onset MG. By contrast, thymoma may be involved in MG etiology in late-onset representing, as such, a useful discriminant tool for MG etiology between early and late-onset MG patients. Because autoimmune phenomena may rise in aging, a parallelism with altered immune functions during aging is discussed.
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Envelhecimento/imunologia , Interleucina-2/imunologia , Interleucina-6/imunologia , Miastenia Gravis/imunologia , Receptores Colinérgicos/imunologia , Fator Tímico Circulante/imunologia , Timoma/complicações , Neoplasias do Timo/complicações , Zinco/imunologia , Adolescente , Adulto , Idoso , Feminino , Humanos , Interleucina-2/sangue , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade , Miastenia Gravis/sangue , Miastenia Gravis/complicações , Miastenia Gravis/cirurgia , Timectomia , Fator Tímico Circulante/análise , Timoma/sangue , Timoma/imunologia , Neoplasias do Timo/sangue , Neoplasias do Timo/imunologia , Fatores de Tempo , Zinco/sangueRESUMO
Changes in transepithelial water and electrolyte transport as causative or contributing factors of the diarrhoea and constipation found associated with changes in thyroid physiology were studied. Albino Wistar rats were pharmacologically made either hypothyroid or hyperthyroid. After sacrifice, the small intestine was mounted in Ussing chambers in order to measure in vitro ion net fluxes under short-circuit conditions. Hypothyroid animals showed an increase in intestinal transit time, Cl- absorption (mainly due to an increment in its mucosal to serosal component) and residual ion flux (which is believed to represent HCO3- secretion) when compared with euthyroid animals. The hyperthyroid animals showed a decrease in Cl- mucosal to serosal transport. Furthermore, a significant correlation was found between serum L-thyroxine (T4) levels and both net Cl- transport (r = -0.74, P < 0.00001) and residual ion flux (r = -0.55, P < 0.005). These results indicate that the effect of T4 is firstly to inhibit Cl-/HCO3- anion exchange thereby influencing transepithelial flux transport and secondly to affect intestinal motility. Such inhibition was not found when T4 was acutely added to rat ileum, suggesting that the effect on electrolyte transport probably requires protein synthesis. In conclusion, the phenomenon observed in vitro could explain the clinical manifestations of constipation and diarrhoea in hypo- and hyper-thyroidism respectively.
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Cloretos/metabolismo , Trânsito Gastrointestinal/efeitos dos fármacos , Absorção Intestinal/efeitos dos fármacos , Doenças da Glândula Tireoide/metabolismo , Tiroxina/farmacologia , Animais , Bicarbonatos/metabolismo , Hipertireoidismo/metabolismo , Hipotireoidismo/metabolismo , Técnicas In Vitro , Intestino Delgado/metabolismo , Transporte de Íons/efeitos dos fármacos , Ratos , Ratos WistarRESUMO
BACKGROUND: The intellectual outcome in children with congenital hypothyroidism detected by neonatal screening is generally good; however, subtle neurological dysfunctions, subnormal IQ, or both, have been reported. OBJECTIVE: To evaluate the intellectual outcome in 12-year-old patients with congenital hypothyroidism, detected by neonatal screening, in an attempt to identify factors that may affect intellectual development. METHODS: The intelligence quotient (IQ) of 40 children with congenital hypothyroidism was evaluated at 12 years of age, using the Wechsler Intelligence Scale for Children -- Revised, and compared with the IQ of 40 healthy siblings (control group). RESULTS: The mean IQ score (88.4+/-13.1) was not significantly different from that of the control group (93.4+/-10.7). Thirteen patients showed subnormal IQ score (72.4+/-4.9) compared with their siblings (86.7+/-9.6; P<0.0001) and with the other patients (96.1+/-9.6; P<0.0001). The low IQ score was associated with lower serum concentrations of thyroxine at diagnosis, poor treatment compliance during follow-up and lower familial IQ. Interviews with parents of children with congenital hypothyroidism revealed that a refusal to acknowledge the disease was linked to poor attention to the child's emotional life and to poor treatment compliance in some cases (11%). CONCLUSION: Even though the mean IQ score in patients with congenital hypothyroidism falls within normal for the control population, low IQ scores may be present in patients with severe hypothyroidism, inadequate compliance to replacement therapy during follow-up and poor parental pedagogic attitude.
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Adaptação Psicológica , Hipotireoidismo Congênito/psicologia , Inteligência , Relações Pais-Filho , Fatores Etários , Estudos de Casos e Controles , Criança , Hipotireoidismo Congênito/sangue , Hipotireoidismo Congênito/congênito , Hipotireoidismo Congênito/tratamento farmacológico , Feminino , Humanos , Testes de Inteligência , Modelos Lineares , Masculino , Núcleo Familiar , Cooperação do Paciente , Prognóstico , Hormônios Tireóideos/sangue , Resultado do TratamentoRESUMO
T-cell growth factor (TCGF) activity was studied in phytohemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PBMC) from 10 type-1 diabetic patients who had been diagnosed within the previous 12 months (group A), from 9 diabetic patients in whom the duration of disease was more than 1 year (group B) and from 12 healthy controls (group C). The effects of indomethacin on PHA-induced TCGF activity and the effects of adherent cells (macrophages) from group A and group C on TCGF production of normal group-matched non-adherent cells (lymphocytes) were also studied. TCGF activity was assayed on TCGF-dependent blast cells and calculated as a stimulation index (SI). TCGF activity in group A (SI 0.86 +/- 0.8) was significantly different from that in group B (SI 1.75 +/- 1.02; P = 0.037) and in group C (SI 1.91 +/- 1.29; P = 0.023). Following the addition of indomethacin, TCGF SI was 1.35 +/- 0.74 in group A, 1.85 +/- 0.73 in group B and 2.06 +/- 1.19 in group C. The responses to indomethacin were found to correlate with the basal TCGF activity in all subjects (r = -0.48; P = 0.006) independently of the disease process studied or its duration. No correlation was found between TCGF activity and parameters of metabolic control (HBA1c and fructosamine). Interestingly, a significant inverse correlation was found between TCGF activity and the required dose of insulin only in group A (r = -0.66; P < 0.05). Adherent cells from diabetic patients were found not to inhibit TCGF production.(ABSTRACT TRUNCATED AT 250 WORDS)
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Diabetes Mellitus Tipo 1/imunologia , Ativação Linfocitária , Linfocinas/biossíntese , Linfócitos T/metabolismo , Adolescente , Bioensaio , Criança , Pré-Escolar , Diabetes Mellitus Tipo 1/sangue , Feminino , Hexosaminas/sangue , Humanos , Indometacina/farmacologia , Interleucina-2/biossíntese , Interleucina-2/imunologia , Ativação Linfocitária/fisiologia , Linfocinas/imunologia , Macrófagos/fisiologia , Masculino , Fito-Hemaglutininas/farmacologia , Linfócitos T/fisiologiaRESUMO
BACKGROUND: Head circumference of children with multiple pituitary-hormone deficiency (MPHD) may be subnormal for age. Moreover it is known that linear growth in infancy is growth-hormone (GH) dependent. Therefore, aim of the study has been to compare head circumference measurements in children with hypopituitarism after L-thyroxine (L-T4) therapy alone, before therapy with GH, and after GH was added to the therapy. METHODS: Five infants (2 girls, 3 boys) with MPHD, diagnosed and treated before the age of 2 years and whose auxological parameters records during L-T4 therapy alone were available, were retrospectively studied. Head circumference and length measurements were expressed as standard deviation score (SDS). Weight measurements were expressed as weight for length ratio percentage. RESULTS: Initially treated with L-T4 alone for a mean period of 4, 5 months, there were neither positive effects on head circumference nor on linear growth. A significant catch-up growth was observed only employing GH therapy in addition to L-T4: mean head circumference SDS and length SDS increased respectively from -2.20 to -0.89 SDS and from -4.16 to -0.87 SDS after a mean period of 18 months of combined GH and L-T4 therapy. CONCLUSIONS: Therefore, head circumference growth, in infancy, is growth hormone dependent as well as linear growth, and during GH treatment, monitoring head circumference growth is important as much as monitoring linear growth.
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Cabeça/crescimento & desenvolvimento , Hormônio do Crescimento Humano/uso terapêutico , Hipopituitarismo/tratamento farmacológico , Tiroxina/uso terapêutico , Quimioterapia Combinada , Feminino , Humanos , Lactente , Masculino , Estudos RetrospectivosRESUMO
The impact of treatment of central precocious puberty (CPP) with gonadotropin-releasing hormone agonists (GnRHa) on final height remains controversial. We analyzed the long term results of 23 girls with CPP treated with triptorelin or leuprolide. Their "near final height" (NFH) assessed at a bone age of at least 14 years and expressed as SDS, was compared either with predicted height before treatment (PAH) or with parental height (TH). We also compared NFH of 12 girls treated before 8 years of age (7.0 +/- 0.5 yr) with NFH of 11 girls treated after 8 years old (8.5 +/- 0.3 yr). The NFH of the 23 girls (-0.9 +/- 1.0 SDS) was not different either from PAH (-0.85 +/- 1.5 SDS) or from TH (-0.5 +/0.6 SDS). Earlier treated girls reached a NFH (-0.97 +/- 1.0 SDS) not different from later treated girls (-0.91 +/- 1.0 SDS; p = ns) and both groups reached parental height (NFH - TH = -0.44 +/- 1 and -0.09 +/- 0.83 SDS, respectively). In conclusion, our patients, treated either earlier or later, reached a near final height comparable to predicted height and familial target; however, these results might still improve further because the girls have not yet reached their final adult height.
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Estatura/efeitos dos fármacos , Encefalopatias/complicações , Hormônio Liberador de Gonadotropina/agonistas , Puberdade Precoce/tratamento farmacológico , Puberdade Precoce/etiologia , Desenvolvimento Ósseo , Criança , Feminino , Humanos , Leuprolida/uso terapêutico , Puberdade Precoce/fisiopatologia , Pamoato de Triptorrelina/uso terapêuticoRESUMO
Polyneuropathy caused by n-hexane contained in glues was, until recently, the typical occupational disease of shoemakers. Glues no longer contain large concentrations of this solvent, and in some cases, it as been completely replaced by other hydrocarbons. The authors investigated the health status in a group of shoemakers using glues containing 35% technical heptane. The same glue, not containing n-hexane, was used by a shoemaker who worked at home; she developed an otherwise unexplainable peripheral polyneuropathy. For each of the 16 subjects, the following procedures were carried out: environmental sampling, biological monitoring for Mek and heptane metabolites, a neurological and electromyographic examination. No neurological abnormalities were found in the workers that could be attributable to occupational exposure, probably due to the low level environmental contamination (< 100 mg/m3 n-heptane) found in the 7 factories and workshops studied where acceptable hygiene conditions existed. The time course and ratio of urinary metabolites of heptane were also studied, the latter showing a predominance of 2- and 3- heptanol in the initial phase and 2-5 heptandione at the end of the work week; probably, the presence of other solvents, such as Mek, can modify the ratio of metabolites and consequently the formation of neurotoxic compounds could result.
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Adesivos/efeitos adversos , Exposição Ambiental , Heptanos/efeitos adversos , Doenças Profissionais/induzido quimicamente , Sapatos , Adulto , Poluentes Ocupacionais do Ar/análise , Eletromiografia , Monitoramento Ambiental , Feminino , Heptanos/metabolismo , Humanos , Masculino , Doenças Profissionais/diagnóstico , Ocupações , Nervos Periféricos/efeitos dos fármacos , Polineuropatias/induzido quimicamente , Polineuropatias/diagnósticoRESUMO
AIM: The authors report the results of a retrospective study carried out with family pediatricians (PDF) in the area of Naples to verify the epidemiology of cryptorchidism and retractile testis, the therapeutic strategy adopted and to assess whether they were in agreement with the data of the scientific literature. METHODS: The study enrolled 6880 children, aged between 0-14 years, till March 2007; among those were recruited the patients with a diagnosis of cryptorchid and/or retractile testis. A patient schedule was completed with the affected side or bilaterality, age at diagnosis, type of treatment and the number of ascent retractile testis. RESULTS: A purely descriptive analysis of the data was carried out: 81 patients were diagnosed with cryptorchid patients (1.18%) and 116 with retractile testis (1.68%). In 11 cases an ascent testicle was detected (9.48%). Forty-nine of the 81 cryptorchid patients (60.49%) were diagnosed in the age group of 0-2 years, 25 (30.86%) between 2-4 years and 7 (8.64 %) between 4-8 years. The hormonal therapy associated with surgery was mainly adopted in cryptorchid patients (35 patients). CONCLUSION: The incidence of cryptorchidism in the area of Naples (1.18%) has not changed significantly. Only 60.49% of patients have been treated in an appropriate age group (0-2 years). The survey confirms the need to follow up the retractile testes for the possibility of definitive ascent in the inguinal canal. The study highlights the need for early diagnosis and treatment of this disease.
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Criptorquidismo/epidemiologia , Criptorquidismo/terapia , Adolescente , Criança , Pré-Escolar , Humanos , Lactente , Itália/epidemiologia , Masculino , Estudos Retrospectivos , Testículo/anormalidadesAssuntos
Hiperplasia Suprarrenal Congênita/sangue , Hiperplasia Suprarrenal Congênita/complicações , Trombocitose/complicações , 17-alfa-Hidroxiprogesterona , Feminino , Humanos , Hidroxiprogesteronas/sangue , Recém-Nascido , Masculino , Contagem de Plaquetas , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Abnormal increments of pro-inflammatory cytokines (IL-6 and TNF-alpha) characterize the outbreak of infectious diseases, which are the major cause of death in the elderly. A counterbalance to the inflammation is exerted by IL-10 with an inhibitory role on TNF-alpha production. As is well known, some cytokine gene polymorphisms influence the cytokine production, playing a role as susceptibility or resistance factors against immune-mediated and infectious disease. Genetic variations in the -308A/G locus for TNF-alpha seems to affect the clinical outcome of some infectious diseases. In fact, the -308A allele is associated with severe septic shock and death. On this basis, we have screened healthy old subjects, nonagenarians and old patients affected by the acute phase of chronic obstructive bronchitis and bronchopneumonia of bacteria origin for the -308G/A locus (PCR-RFLP). Subjects are grouped in A+ (AG, AA genotypes) and A- (GG genotype) and data on IL-6, TNF-alpha, IL-10, NK cell cytotoxicity, zinc and metallothioneins (MTs) gene expression (RT-PCR) were stratified according to different TNF-alpha genotypes. The frequency of the A allele was increased in infected patients in comparison with healthy old controls. No differences existed between A+ and A- young adult, old and nonagenarian controls in tested parameters. Conversely, A+-infected patients displayed elevated IL-6, TNF-alpha and MTmRNA, low IL-10 coupled with impaired NK cell cytotoxicity and lower zinc ion than A- patients. However, the data reported are gender independent. Therefore, the -308A polymorphism at the locus of TNF-alpha may be one of the susceptibility factor for infectious diseases in old persons, particularly considering its association to the increased release of pro-inflammatory cytokines and to the reduction of zinc release and MTs synthesis involved in the control of the inflammatory response. These data strongly suggest that the genetic screening of the -308G/A polymorphism may be a valid tool for identification of subjects needing a more appropriate therapy when affected by acute and/or recurrent infectious diseases.
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Doenças Transmissíveis/genética , Polimorfismo Genético , Fator de Necrose Tumoral alfa/genética , Adulto , Idoso , Bronquite Crônica/genética , Bronquite Crônica/imunologia , Bronquite Crônica/microbiologia , Broncopneumonia/genética , Broncopneumonia/imunologia , Broncopneumonia/microbiologia , Doenças Transmissíveis/imunologia , Feminino , Frequência do Gene , Genótipo , Humanos , Interleucina-6/genética , Interleucina-6/metabolismo , Células Matadoras Naturais/imunologia , Masculino , Metalotioneína/metabolismo , Pessoa de Meia-Idade , Zinco/metabolismoRESUMO
This study was designed to evaluate whether a single blood sample drawn after the home injection of a long-acting gonadotropin-releasing hormone (GnRH) agonist (GnRHa) in patients treated for central precocious puberty (CPP) could be a more simple and inexpensive test with respect to the conventional GnRH stimulating test in assessing adequate suppression of the pituitary-gonadal axis. The response to the first therapeutic injection of the GnRHa triptorelin was studied in 14 newly diagnosed untreated females with CPP. The results were compared with the response that the same patients had to the conventional GnRH stimulation test performed at the time of diagnosis. A significant increase in LH, FSH and E2 levels was observed 12 h after the triptorelin intramuscular injection; serum peak values of LH (70.3 +/- 58.5 IU/l), FSH (44.2 +/- 21.7 IU/l) and E2 (489.7 +/- 263.9 pmol/l) were significantly greater than those obtained with the conventional GnRH test (LH 31.4 +/- 21.7, p = 0.002; FSH 19.8 +/- 10. 7, p = 0.001; E2 83.3 +/- 25, p < 0.001). In particular, the E2 response, 12 h after triptorelin injection, was clearly consistent with gonadal activation compared to the modest E2 increase in response to the GnRH test. Thereafter 22 girls who were already being treated with triptorelin for CPP were evaluated to see whether a single blood sample drawn 12 h after the therapeutic home injection of GnRHa could be informative in assessing adequate suppression of the pituitary-gonadal axis. This response was also compared to the conventional GnRH stimulation test performed 2 days before the therapeutic triptorelin injection. In 7 girls with evidence of pubertal progression, the E2 response following the GnRHa injection (136.3 +/- 44.4 pmol/l) was significantly higher with respect to the response after the GnRH stimulation test (73.0 +/- 0.0; p < 0.02) indicating an inadequate suppression of the pituitary-gonadal axis. The present data suggest that a single blood sample drawn 12 h after the therapeutic home administration of triptorelin provides a simple, comfortable and inexpensive means of monitoring pituitary as well as gonadal function in girls treated for CPP.
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Puberdade Precoce/sangue , Pamoato de Triptorrelina/uso terapêutico , Criança , Estradiol/sangue , Feminino , Hormônio Foliculoestimulante/sangue , Humanos , Injeções Intramusculares , Cinética , Hormônio Luteinizante/sangue , Puberdade Precoce/tratamento farmacológico , Pamoato de Triptorrelina/administração & dosagemRESUMO
BACKGROUND: Head circumference of children with multiple pituitary-hormone deficiency (MPHD) may be subnormal for age. Moreover it is known that linear growth in infancy is growth-hormone (GH) dependent. Therefore, aim of the study has been to compare head circumference measurements in children with hypopituitarism after L-thyroxine (L-T4) therapy alone, before therapy with GH, and after GH was added to the therapy. METHODS: Five infants (2 girls, 3 boys) with MPHD, diagnosed and treated before the age of 2 years and whose auxological parameters records during L-T4 therapy alone were available, were retrospectively studied. Head circumference and length measurements were expressed as standard deviation score (SDS). Weight measurements were expressed as weight for length ratio percentage. RESULTS: Initially treated with L-T4 alone for a mean period of 4, 5 months, there were neither positive effects on head circumference nor on linear growth. A significant catch-up growth was observed only employing GH therapy in addition to L-T4: mean head circumference SDS and length SDS increased respectively from -2.20 to -0.89 SDS and from -4.16 to -0.87 SDS after a mean period of 18 months of combined GH and L-T4 therapy. CONCLUSIONS: Therefore, head circumference growth, in infancy, is growth hormone dependent as well as linear growth, and during GH treatment, monitoring head circumference growth is important as much as monitoring linear growth.
Assuntos
Cabeça/anatomia & histologia , Hormônio do Crescimento Humano/uso terapêutico , Hipopituitarismo/tratamento farmacológico , Tiroxina/uso terapêutico , Adolescente , Antropometria , Criança , Feminino , Humanos , Masculino , Estudos RetrospectivosRESUMO
UNLABELLED: We evaluated whether hepatic abnormalities represent a specific feature in girls with Turner syndrome (TS) or whether they are related to an increased susceptibility to hormonal therapies and/or other factors. Alanine aminotransferase, aspartate aminotransferase and gamma-glutamyl transferase were monitored in 70 patients with TS for a mean period of 7.6+/-4.2 years. An increase in serum liver enzymes was observed in 14 out of 70 girls (20%) at a mean age of 12.7 years; it was present at entry before hormonal therapy in 3 girls and developed thereafter during the follow up in the other 11. The increase in serum liver enzymes was never observed before the age of 7 years. In the majority of cases (10/14) it was drug related: in 50% the liver abnormalities were transient and self-limiting, in the remaining cases they required interruption of hormonal therapy. Hepatotoxicity was more frequently observed in girls treated with oestrogens or oxandrolone than in those treated with growth hormone. In a small number of cases, liver disease was either auto-immunity-related (2/14), or cryptogenic (1/14) with a benign and self-limiting course. Obesity was a frequent finding, but it played a likely pivotal role only in one patient. CONCLUSION: Hepatic abnormalities are relatively frequent in Turner syndrome and surveillance of liver function should be included in the management of these patients independent of initiation of hormonal treatment.