Obesity,metabolic health and omics: Current status and future directions

The growing obesity epidemic is becoming a major public health concern, and the associated costs represent a considerable burden on societies. Among the most common complications of severe obesity are the development of hypertension, dyslipidemia, type 2 diabetes, cardiovascular disease, and various types of cancer. Interestingly, some obese individuals have a favorable metabolic profile and appear to be somehow protected from the detrimental effects of excessive adipose tissue accumulation. These individuals remain normoglycemic, insulin sensitive, and hypotensive with proper blood lipid levels, despite their high body mass index and/or waist circumference. Multiple independent observations have led to the concept of the metabolically healthy obese (MHO) phenotype, yet no consensus has been reached to date regarding a universal definition or the main mechanism behind this phenomenon. Recent technological advances and the use of high-throughput analysis techniques have revolutionized different areas of biomedical research. A multi-omics approach, which is used to investigate changes at different molecular levels in an organism or tissue, may provide valuable insights into the interplay between the molecules or pathways and the roles of different factors involved in the mechanisms underlying metabolic health deterioration. The aim of this review is to present the current status regarding the use of omics technologies to investigate the MHO phenotype, as well as the results of targeted analyses conducted in MHO individuals.     

Primary and acquired drug resistance of tuberculosis bacilli in Poland

Information about resistant pattern of Mycobacterium tuberculosis isolates against antituberculon drugs is a very important part of tuberculosis control and indicates the directions of TB policy in each country. Poland joined WHO/IUATLD global project on drug resistance surveillance, and carried out the first prospective survey, simultaneously on primary and acquired drug resistance of tuberculosis patients according WHO/IUATLD recommendations. The programme covered the whole country, basing on cooperation between the National Reference Laboratory (NRL) with regional TB laboratories. Questionnaires and cultures were obtained from patients who excreted TB bacilli during the period from 1 November 1996 to 1 November 1997 (12 months). Drug susceptibility testing to INH, SM, EMB and RMP were performed on Lowenstein-Jensen medium according to the proportion method or/and radiometric Bactec 460 TB system. 3970 TB patients bacteriologically confirmed by culture were included in a one-year study. The male to female ratio was 2.6:1. Patients were at the age of 6 to 83 years. Majority of patients (86% males and 77% of females) was older than 35 years. Primary resistance to any drug was found in 3.6% of new cases and 2.4% of those patients who excreted monoresistant strains. No monoresistance to EMB was found. 18 patients (0.6%) were infected by MDR strains. Total resistance in new cases was for INH--2.6%, for SM--1.8%, for RMP--0.7% and for EMB--0.1%. Acquired resistance to any drug was found in 17.0% of treated. Majority of patients--7.7% excreted monoresistant strains. 7.0% were infected by MDR strains. Total resistance to INH was 14.8%, to SM--9.2%, to RMP--7.8%, and to EBM--2.5%. No correlation was found between sex and primary resistance rates. Among new cases, 3.7% of males and 3.3% of females were infected with resistant strains. However, among treated patients, males (20%) excreted resistant strains twice as much as females (9.1%). Mean age of women and men infected with primary and acquired resistant strains was similar.     

Inhibition of cyclooxygenase-2 indirectly potentiates antitumor effects of photodynamic therapy in mice.

PURPOSE: The aim of the present study was to potentiate the antitumor effectiveness of photodynamic therapy (PDT). A cDNA microarray analysis was used to evaluate the gene expression pattern after Photofrin-mediated PDT to find more effective combination treatment with PDT and inhibitor(s) of the identified gene product(s) overexpressed in tumor cells. EXPERIMENTAL DESIGN: Atlas Mouse Stress Array was used to compare the expression profile of control and PDT-treated C-26 cells. The microarray results have been confirmed using Western blotting. Cytostatic/cytotoxic in vitro assay as well as in vivo tumor models were used to investigate the antitumor effectiveness of PDT in combination with cyclooxygenase (COX) 2 inhibitors. RESULTS: PDT induced the expression of 5 of 140 stress-related genes. One of these genes encodes for COX-2, an enzyme important in the tumor progression. Inhibition of COX-2 in vitro with NS-398, rofecoxib, or nimesulide, or before PDT with nimesulide did not influence the therapeutic efficacy of the treatment. Administration of a selective COX-2 inhibitor after PDT produced potentiated antitumor effects leading to complete responses in the majority of treated animals. CONCLUSIONS: COX-2 inhibitors do not sensitize tumor cells to PDT-mediated killing. However, these drugs can be used to potentiate the antitumor effectiveness of this treatment regimen when administered after tumor illumination.     

Anxiety and depression and their influence on the quality of life after total hip replacement: preliminary report

Objective. The study investigated health-related quality of life in relation to mental status (anxiety and depression) and demographic factors in patients before and after total hip replacement due to osteoarthrosis. Methods. The SF-36, HADS, socio-demographic data questionnaire was delivered to a group of 184 subjects (108 females, 76 males) at the mean age at the time of surgery of 59 years. Questionnaires were delivered to the subjects 2 weeks before the surgery and 6 months after the operation (by mail). Results. Patients after hip replacement showed significant improvement in health-related quality of life in most domains of SF-36 score and summary scale of PCS (Physical Component Summary Scale) and MCS (Mental Component Summary Scale). They also showed improvement in mental status. Elderly patients were more likely to show worse score in MCS and PCS before and after surgery. BMI (body mass index) was correlated only with preoperative PCS. Mental status was associated with postoperative PCS and MCS. Patients who were satisfied with the results of the surgery showed higher PCS and MCS score. Conclusion. Hip replacement surgery brings significant improvement to the quality of life. Age and mental status of those patients influence markedly their postoperative performance.