Associations between anthropometric indicators in early life and low-grade inflammation,insulin resistance and lipid profile in adolescence

Background and aimsThe long-term relations between excessive adiposity in early childhood and unfavourable cardiometabolic profiles in later ages are not yet completely understood. We aimed to assess the associations between birth weight (BW) and BMI from 6 months to 6 years of age, with biomarkers indicative of low-grade inflammation, insulin resistance and lipid profiles in adolescence.Methods and resultsRetrospective school-based study with 415 Portuguese adolescents (220 girls), mean age of 14.08 ± 1.6 years old. Anthropometric data from birth to 6 years old was extracted from individual child health book records. Actual weight and height were measured and BMI calculated. Participants were classified at each time point as normal weight or overweight according to WHO reference values. Biomarkers were obtained from venous blood samples. Linear regressions were used to explore the associations between the biomarkers and early life anthropometric indicators. From 2 years onwards, BMI associated positively with the inflammatory score and HOMA-IR in adolescence. Children who were overweight/obese from 2 to 6 years of age presented significantly higher inflammatory score and HOMA-IR later in adolescence. TC/HDL ratio was also positively associated with BMI from the age of 5 years onwards. The associations between BMI and cardiometabolic outcomes remained positive in adolescence, with overweight adolescents presenting a higher inflammatory score, HOMA-IR and TC/HDL than normal weight adolescents.ConclusionA high BMI from an early age was consistently associated with worse inflammatory and lipid profiles and insulin resistance in adolescence. No associations were found between BW and the same studied outcomes.     

Localized Kaposi''s sarcoma in a patient with pemphigus vulgaris

We report the case of a patient with a 13-year history of pemphigus vulgaris (PV) treated with immunosuppressive agents, prednisone and mycophenolate mofetil who had developed lesions of Kaposi's sarcoma (KS) on a sole plaque of PV that had been previously treated with intralesional injections of steroids. The lesions were surgically removed and polymerase chain reaction (PCR) demonstrated human herpesvirus-8 (HHV-8) DNA. There were neither recurrences nor later dissemination of KS following gradual decrease of the immunosuppressive therapy. We suggest that the treatment with intralesional steroids may have influenced the local reactivation of a latent infection of the virus, determining the appearance of this localized KS.     

Effect of sorbinil on blood-retinal barrier in early diabetic retinopathy

To study the effect of sorbinil on the alteration of the blood-retinal barrier, 32 adult-onset, non-insulin-dependent diabetic patients with minimal or no retinopathy were randomly assigned to receive either oral sorbinil (250 mg once a day) or a placebo for 6 mo. All patients underwent fundus photography, fluorescein angiography, and vitreous fluorophotometry before treatment and at 3 and 6 mo after treatment. Vitreous fluorophotometry data showed that the alteration of the blood-retinal barrier increased significantly less in the sorbinil-treated group compared with the placebo group during the 6-mo study period. Side effects were limited to hypersensitivity reactions, with skin rash and fever, in only 2 of the 16 patients who received the drug. These hypersensitivity reactions disappeared with discontinuation of the medication. Aldose-reductase inhibition may play an important role in stabilization of the blood-retinal barrier in early diabetic retinopathy.     

Flerobuterol: a potential antidepressant drug related to β-adrenergic agonists. Experimental profile in mice

The potential antidepressant effect of flerobuterol (dl-(fluoro-2 phenyl)-1 t-butylamino-2 ethanol), a new drug related to beta-adrenoceptor agonists, was evaluated and compared with imipramine and salbutamol using classical psychopharmacological tests in mice. Like imipramine and salbutamol, flerobuterol (0.5-32 mg kg-1, ip) fully prevented apomorphine (16 mg kg-1, sc)- and partly reversed reserpine- and oxotremorine-induced hypothermia. At higher doses (16-32 mg kg-1), flerobuterol enhanced the toxic effects of yohimbine. Unlike imipramine, flerobuterol and salbutamol did not reduce immobility duration in the behavioural despair test. Salbutamol and flerobuterol decreased locomotor activity. Flerobuterol did not induce mydriasis, did not prevent oxotremorine-induced tremors or salivary and lacrimal gland secretion and did not reduce reserpine-induced palpebral ptosis. Propranolol (8 mg kg-1, ip) but not alpha-methyl-paratyrosine (75 mg kg-1, ip) prevented the flerobuterol-induced antagonism of apomorphine-induced hypothermia. Our results suggest that flerobuterol demonstrates potential antidepressant activity, which could be related to beta-adrenoceptor activation in mice.     

Retrospective review of pemetrexed with or without platinum in malignant mesothelioma: The Australian 'Special Access Scheme' experience

Background: Pemetrexed and cisplatin have recently been shown to significantly improve survival compared with cisplatin alone. However, there are only limited data reflecting teaching hospital experience outside a clinical trial. Pemetrexed has only been available in Australia on a restricted basis since 2002. We reviewed our experience of patients treated on the Australian ‘Special Access Scheme’ at three major thoracic oncology units. Methods: Charts were reviewed for all patients enrolled on the scheme. Data was extracted on age, World Health Organization (WHO) performance status, histology, prior therapy, time from diagnosis to starting pemetrexed, chemotherapy (pemetrexed alone or with a platinum), cycle number, response rate, actuarial progression‐free and overall survival. Doses were cisplatin 75 mg/m² or carboplatin AUC = 5 and pemetrexed 500 mg/m² every 21 days. Results: 52 patients (32 male and 20 female) were reviewed. Median age was 58 years and 88% were WHO 0–1. Histology included 54% epithelial, 17% biphasic (epithelial and sarcomatoid) and 21% undefined. The median time from diagnosis to administration of pemetrexed was 145 days. Sixty‐five percent had minimal surgical intervention with video assisted thoracoscopy, pleurodesis and biopsy, while 19% had received prior palliative radiation. Seventy‐one percent were chemotherapy naïve, the remaining 29% having received previous platinum and/or gemcitabine regimens. Twenty‐three percent had pemetrexed alone, 35% in combination with carboplatin and 42% with cisplatin. The median number of cycles was 4 (range 1–13). The response rate was 33%. No toxicity was observed in 20% grade 3–4 toxicity in 10% (majority nausea/vomiting). The median progression‐free and overall survival times from starting pemetrexed were 184 days and 298 days, respectively. Conclusions: Pemetrexed‐based regimens are safe and effective in a community setting in malignant mesothelioma.     

Apoptosis and asthma in the elderly.

BACKGROUND: Asthma is a chronic inflammatory disorder of the airways. The persistence of airway inflammation depends on a decrease in apoptosis of T lymphocytes and eosinophils and survival of these activated cells. T lymphocytes expressing gamma delta receptors can be identified in human lungs and play an important role in immune defence against pathogens and in the regulation of chronic inflammation. Aging is associated with evidence of some immune dysregulation. OBJECTIVE: The aim of this study was to analyze the apoptosis receptors of T lymphocytes in long-lasting asthma, to establish their correlation with activation markers such as CD25+ and human leukocyte antigen (HLA)-DR+, and to analyze the gama delta T cell expression in this disease. METHODS: A group of 64 individuals (group A) who had had asthma for more than 30 years (mean age [+/-SD] 72 +/- 5 years) and 61 healthy individuals acting as controls--group B with 41 individuals (mean age 79 +/- 7 years) and group C with 20 individuals (mean age 38 +/- 12 years) were included in the study. All subjects underwent clinical evaluation and spirometric testing. Peripheral blood cells were stained with monoclonal antibodies anti-CD3, anti-CD4, anti-CD8, anti-CD25, anti-TCR gamma delta, anti-HLA-DR and anti-CD95. Statistical comparisons were performed between the asthmatics and the elderly control group and between the elderly control group and the adult control group. RESULTS: The average percentage of predicted forced expiratory volume in the first second was 73.6 gamma delta 25.3. The mean values of T cell receptors for asthma group A vs elderly control group B vs adult control group C respectively, were the following: CD3, 74.9+/-7 vs. 74.8 +/- 8.8 (P=ns) vs. 76.7 +/- 4.2 (P=ns); CD4, 48.8 +/- 8.7 vs. 43.5 +/- 10.2 (P=ns) vs. 44.8 +/- 3.8 (P=ns); CD8, 23.3 +/- 7.9 vs. 25.7 +/- 10.2 (P=ns) vs. 25.6 +/- 4.5 (P=ns); CD25, 14.3 +/- 5.9 vs. 22.4 +/- 7.8 (P = .0001) vs. 5.5 +/- 2.4 (P = .0001); TCR gamma delta, 2.8 +/- 2.1 vs. 4.1 +/- 3.3 (P < .05) vs. 4.6 +/- 2.1 (P=ns); HLA-DR, 18.4 +/- 9.2 vs. 17.8 +/- 5.9 (P=ns) vs. 15.4 +/- 5.1 (P=ns) and CD95, 49.3 +/- 13.7 vs. 52.6 +/- 12.1 (P=ns) vs. 13.8 +/- 10.8 (P = .0001). CONCLUSIONS: The immunological and inflammatory changes related to ageing may cause an increase in CD95 and CD25 T cell expression. In asthma, blood cells may express increased activation and apoptosis markers but in elderly patients taking steroids, these receptors remain within normal ranges. The number of gamma delta T cells may be lower in long-lasting asthma, and have a limited modulatory effect on allergic inflammatory reactions. The evaluation of patients with long-lasting asthma should take into account the immunological and inflammatory changes present in the elderly in order to avoid results being misinterpreted.