Georgios S. Papaetis

Central obesity, type 2 diabetes and insulin: exploring a pathway full of thorns

The prevalence of type 2 diabetes (T2D) is rapidly increasing. This is strongly related to the contemporary lifestyle changes that have resulted in increased rates of overweight individuals and obesity. Central (intra-abdominal) obesity is observed in the majority of patients with T2D. It is associated with insulin resistance, mainly at the level of skeletal muscle, adipose tissue and liver. The discovery of macrophage infiltration in the abdominal adipose tissue and the unbalanced production of adipocyte cytokines (adipokines) was an essential step towards novel research perspectives for a better understanding of the molecular mechanisms governing the development of insulin resistance. Furthermore, in an obese state, the increased cellular uptake of non-esterified fatty acids is exacerbated without any subsequent β-oxidation. This in turn contributes to the accumulation of intermediate lipid metabolites that cause defects in the insulin signaling pathway. This paper examines the possible cellular mechanisms that connect central obesity with defects in the insulin pathway. It discusses the discrepancies observed from studies organized in cell cultures, animal models and humans. Finally, it emphasizes the need for therapeutic strategies in order to achieve weight reduction in overweight and obese patients with T2D.

Chlamydophila pneumoniae infection and COPD: More evidence for lack of evidence?

Chlamydophila pneumoniae has been recognized as a common cause of respiratory tract infections affecting all age groups. The organism has been implicated as an infectious trigger for acute exacerbations of COPD. Moreover, the intracellular existence of this pathogen and the ability to cause chronic respiratory infections have led to a number of studies that investigated its possible association with disease development. The present paper examines and discusses the possible association of acute C. pneumoniae infection in episodes of acute exacerbation of COPD. It also reviews the existing evidence of chronic C. pneumoniae infection with disease pathogenesis and severity. The significant interstudy variation of the choice of diagnostic methods and criteria applied is most likely responsible for the great diversity of results observed. The use of well-standardized, commercially available diagnostic tools, as well as the adoption of a more unified diagnostic approach is probably the key element missing in order to clarify the exact role of C. pneumoniae in COPD.

Asymptomatic stage I sarcoidosis complicated by pulmonary tuberculosis: a case report

IntroductionSarcoidosis is a multisystem granulomatous disorder characterized pathologically by the presence of non-caseating granulomas in involved tissues. Depressed cellular immunity predisposes patients to infections with certain intracellular organisms, mostly fungi, Mycobacterium tuberculosis and Nocardia species. As these infections are mainly insidious and difficult to differentiate from the underlying disease, a possible misdiagnosis may lead to fatal complications for the patient.Case presentationWe present a case of a 67-year-old woman with undiagnosed asymptomatic stage I sarcoidosis for at least 8 years before her admission and a 1-month history of fever, exertional dyspnea and dry cough, in whom pulmonary tuberculosis was documented.ConclusionThis case highlights the need for great vigilance among physicians in order to rule out any possible infection before establishing the diagnosis of sarcoidosis.

Polymorphisms of the NRAMP1 gene: distribution and susceptibility to the development of pulmonary tuberculosis in the Greek population.

Summary Background Ample evidence suggests that host genetic factors affect human susceptibility to tuberculosis. The natural resistance–associated macrophage protein 1 (NRAMP1) gene seems to play a role in the pathophysiology of a number of intracellular infections, including mycobacteria. A case-control study was conducted in the Greek population to determine whether NRAMP1 polymorphisms affect the susceptibility to development of overt pulmonary tuberculosis. Material/Methods NRAMP1 polymorphisms (3′UTR, D543N, INT4) were evaluated among 142 patients with culture-positive pulmonary tuberculosis and 144 ethnically matched healthy controls having latent M. tuberculosis infection. Patients with human immunodeficiency virus infection were excluded. Results Out of the 3 NRAMP1 polymorphisms, a trend of increased incidence of INT4 polymorphism was found in the patients’ group compared to the control group. A lack of association was observed between the 2 groups as far as the other 2 polymorphisms (D543N, 3′UTR) are concerned. INT4-CC homozygotes were found to have a higher risk to develop pulmonary tuberculosis compared to GG homozygotes (p=0.022). An increased incidence G/TGTG/C genotype combination was found in the patients’ group as compared to controls. G/TGTG/C genotype combination was associated with a 36% higher risk of developing pulmonary tuberculosis (p=0.004) compared to the baseline expression of G/TGTG/G combination. Conclusions INT4-NRAMP1 polymorphism may have a role in the development of culture-positive pulmonary tuberculosis after an initial M. tuberculosis latent infection. The possible role of INT4-NRAMP1 polymorphism in the development of active pulmonary tuberculosis needs further investigation.

Serological evidence of Mycoplasma pneumoniae infection in patients with acute exacerbation of COPD: analysis of 100 hospitalizations.

PURPOSE A prospective study was conducted in order to investigate the serologic evidence of Mycoplasma pneumoniae infection in Greek hospitalized patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Furthermore, we have assessed the frequency of a number of variables in the group of patients with a serological diagnosis of an acute M. pneumoniae infection compared to patients in whom M. pneumoniae infection was not documented. MATERIALS/METHODS One hundred patients with AECOPD were enrolled in a 29- month study period. Serum IgG, IgA and IgM M. pneumoniae antibody titers were determined during the first day of their hospitalization and 30 days after enrolment, using a commercial ELISA. RESULTS Nine patients (9%) had serological evidence of an acute M. pneumoniae infection. Acute infection was mainly documented by IgA antibody titer changes. It was mainly attributed to a reinfection rather than a primary infection. Patients with serological evidence of an acute M. pneumoniae infection had a higher heart rate (99±12 versus 88±14 beats/minute, p=0.02) and a higher hematocrit value (47±4.5% versus 40.4±6.2%, p=0.004) at admission than patients without a serological diagnosis for this pathogen. CONCLUSIONS Serologic evidence of M. pneumoniae infection is rather common in Greek hospitalized patients with AECOPD. The determination of all three antibody classes was necessary in order to obtain an optimal level of serodiagnosis. No differences were found in the majority of characteristics of patients with and without serological evidence for this pathogen. The clinical utility of these results should be further clarified in future studies.