Adverse environmental conditions influence age-related innate immune responsiveness

Hutchinson-Gilford progeria syndrome (HGPS) is a rare premature aging disorder that belongs to a group of conditions called laminopathies which affect nuclear lamins. Mutations in two genes, LMNA and ZMPSTE24, have been found in patients with HGPS. The p.G608G LMNA mutation is the most commonly reported mutation. The aim of this work was to compile a comprehensive literature review of the clinical features and genetic mutations and mechanisms of this syndrome as a contribution to health care workers. This review shows the necessity of a more detailed clinical identification of Hutchinson-Gilford progeria syndrome and the need for more studies on the pharmacologic and pharmacogenomic approach to this syndrome.     

An introduction to provisional stenting

Provisional or conditional stenting should be defined as the use of stents limited to those conditions and cases in which the operator, despite an aggressive balloon angioplasty technique with large balloons and high pressure, has been unable to obtain a result that ensures optimal chances of early and late patency. The paramount issue is how to discriminate the patients with optimal results after balloon angioplasty for whom additional stent implantation is unlikely to improve or may even worsen long-term outcome. The better results of elective stent implantation in the OPUS study suggest that visual assessment of the PTCA result is not sufficient to detect lesions with suboptimal lumen gain after PTCA. The addition of physiologic parameters (Doppler flow velocity measurements, fractional flow reserve) has improved the results of the provisional stent group, with the best outcome observed when complex lesions and multivessel treatment were included in these studies (FROST, DESTINI). Intravascular ultrasound, although more expensive and time-consuming, has the additional advantage to guide the dilatation strategy.     

Age at menopause in Puebla,Mexico

Comparisons of age at menopause are made difficult by the different methodologies applied across populations. This study extended an opportunity to apply different methodologies to the same data to draw some preliminary conclusions about age at menopause in Puebla, Mexico. Among 755 women aged 28 to 70 interviewed in the capital city of Puebla, Mexico, 447 (59.6%) were naturally or surgically postmenopausal. Mean recalled age at natural menopause in Puebla (46.7 years) appears to be similar to mean recalled age at menopause in Mexico City (46.5 years), suggesting that age at menopause is similar in urban Mexican populations. However, median age at menopause computed by probit analysis was later in the city of Puebla (49.6 years) compared to the median age computed by the same method in the capital city of León, Guanajuato, Mexico (48.2 years). Median age at menopause computed by Kaplan-Meier survival analysis suggests that age at menopause in Puebla (50.0 years) is older still, and close to that of the United States (51.1 years). The differences in median ages at menopause in Puebla are solely due to methodological choices and highlight the difficulty inherent in making inferences across studies of age at menopause between biological and/or cultural groups. Factors associated with age at menopause offer another avenue for comparing and understanding variation in this basic biological process. In Puebla, smoking, low levels of education, and nulliparity are associated with an earlier age at menopause.     

The medicalization of female fertility--points of significance for the study of menopause

This paper illustrates the need for human biologists to take into account the far-reaching influences of biomedicine in the study of reproductive aging. Data were drawn from western Massachusetts and Puebla, Mexico, to illustrate the effects of hysterectomy rates, tubal ligations and hormone replacement therapy (HRT) on studies of age and symptom experience at menopause. First, in examining age at natural menopause in relation to level of education, a country-specific, non-random pattern of participant exclusion due to hysterectomies was encountered. Second, in examining symptom frequency in relation to late childbearing, sample sizes were very small in part due to a high frequency of tubal ligations (43%) in Puebla, Mexico. Third, hot flash frequency during the two weeks prior to interview was, unexpectedly, not lower among women who used HRT. Human biologists who study the biological process of reproductive aging must also attend to the cultural influences of biomedicine.     

The Influence of Reactive Oxygen Species on the Adhesion of Pancreatic Carcinoma Cells to the Peritoneum

Postoperative peritoneal carcinomatosis is a significant clinical problem after “curative” resection of pancreatic carcinoma. Preoperative surgical trauma activates a cascade of peritoneal defense mechanisms responsible for postoperative intra-abdominal tumor recurrence. Reactive oxygen species (ROS) play a pivotal role in this postoperative inflammatory reaction. This study explores the influence of ROS on adhesion of human pancreatic carcinoma cells to human mesothelial cells. Furthermore this study explores the influence of ROS on the presentation of adhesion molecules on Panc-1 and mesothelial cells. ROS were produced using the enzymatic reaction of xanthine with xanthine oxidase (X/XO). A reproducible in vitro assay to study adhesion of human Panc-1 carcinoma tumor cells to a mesothelial cell monolayer of primary human mesothelial cells was used. Mesothelial monolayers were incubated with ROS produced prior to adhesion of the tumor cells. Incubation of the mesothelial cells with X/XO resulted in a significant increase (69.5%) in adhesion of Panc-1 in all patients. SOD/catalase, anti-oxidants, could reduce this increase by 56.7%. ROS significantly influenced the expression of the adhesion molecules ICAM-1, VCAM-1 and CD44h on mesothelial cells, but did not influence adhesion molecule expression on Panc-1. The ROS released during the post-operative inflammatory reaction may play an important role in the adhesion of pancreatic tumor cells to the mesothelium-possibly by influencing adhesion molecule expression on mesothelial cells. Therefore ROS can partly be responsible for the enhanced post-operative intra-abdominal tumor recurrence.Key words: reactive oxygen species, mesothelium, Panc-1     

Creatine kinase isoenzyme activity during and after an ultra-distance (200 km) run

It is commonly assumed that creatine kinase (CK) activity in plasma is related to the state of an inflammatory response at 24-48 h, and also it has shown biphasic patterns after a marathon run. No information is available on CK isoenzymes after an ultra-marathon run. The purpose of the present study is to examine the CK isoenzymes after a 200 km ultra-marathon run and during the subsequent recovery. Blood samples were obtained during registration 1 2 h before the 200-km race and during the race at 100 km, 150 km and at the end of 200 km, as well as after a 24 h period of recovery. Thirty-two male ultra-distance runners participated in the study. Serum CPK showed a marked increase throughout the race and 24 h recovery period (p < 0.001). Serum CK during the race occurs mostly in the CK-MM isoform and only minutely in the CK-MB isoform and is unchanged in the CK-BB isoform. High-sensitivity C-reactive protein (hs-CRP), oestradiol, AST and ALT increased significantly from the pre-race value at 100 km and a further increase took place by the end of the 200 km run. The results of our study demonstrate a different release pattern of creatine kinase after an ultra-distance (200 km) run compared to the studies of marathon running and intense eccentric exercise, and changes in several biomarkers, indicative of muscle damage during the race, were much more pronounced during the latter half (100–200 km) of the race. However, the increases in plasma concentration of muscle enzymes may reflect not only structural damage, but also their rate of clearance.     

Calibration of mammalian skeletal muscle Ca2+ transients recorded with the fast Ca2+ dye Mag-Fluo-4

BackgroundMag-Fluo-4 is increasingly employed for studying Ca²⁺ signaling in skeletal muscle; however, the lack of information on the Ca²⁺-Mag-Fluo-4 reaction limits its wider usage.MethodsFluorescence and isothermal titration calorimetry (ITC) experiments were performed to determine the binding stoichiometry (n) and thermodynamics (enthalpy (ΔH) and entropy (ΔS) changes), as well as the in vitro and in situ K_d of the Ca²⁺-Mag-Fluo-4 reaction. Rate constants (k_on, k_off), fluorescence maximum (F_max), minimum (F_min), and the dye compartmentalization were also estimated. Experiments in cells used enzymatically dissociated flexor digitorum brevis fibres of C57BL6, adult mice, loaded at room temperature for 8 min, with 6 μM Mag-Fluo-4, AM, and permeabilized with saponin or ionomycin. All measurements were done at 20 °C.ResultsThe in vitro fluorescence assays showed a binding stoichiometry of 0.5 for the Ca²⁺/Mag-Fluo-4 (n = 5) reaction. ITC results (n = 3) provided ΔH and ΔS values of 2.3 (0.7) kJ/mol and 97.8 (5.9) J/mol.K, respectively. The in situ K_d was 1.652 × 10⁵μM²(n = 58 fibres, R² = 0.99). With an F_max of 150.9 (8.8) A.U. (n = 8), F_min of 0.14 (0.1) A.U. (n = 10), and ΔF of Ca²⁺ transients of 8.4 (2.5) A.U. (n = 10), the sarcoplasmic [Ca²⁺]_peak reached 22.5 (7.8) μM. Compartmentalized dye amounted to only 1.1 (0.7)% (n = 10).CONCLUSIONS: Two Mag-Fluo-4 molecules coalesce around one Ca²⁺ ion, in an entropy-driven, very low in situ affinity reaction, making it suitable to reliably track the kinetics of rapid muscle Ca²⁺ transients.General significanceOur results may be relevant to the quantitative study of Ca²⁺ kinetics in many other cell types.     

Methicillin-Resistant Staphylococcus aureus USA300 Latin American Variant in Patients Undergoing Hemodialysis and HIV Infected in a Hospital in Bogotá, Colombia

We aimed to determine the prevalence of MRSA colonization and examine the molecular characteristics of colonizing isolates in patients receiving hemodialysis and HIV-infected in a Colombian hospital. Patients on hemodialysis and HIV-infected were prospectively followed between July 2011 and June 2012 in Bogota, Colombia. Nasal and axillary swabs were obtained and cultured. Colonizing S. aureus isolates were identified by standard and molecular techniques. Molecular typing was performed by using pulse-field gel electrophoresis and evaluating the presence of lukF-PV/lukS-PV by PCR. A total of 29% (n = 82) of HIV-infected and 45.5% (n = 15) of patients on hemodialysis exhibited S. aureus colonization. MSSA/MRSA colonization was observed in 28% and 3.6% of the HIV patients, respectively and in 42.4% and 13.3% of the hemodialysis patients, respectively. Staphylococcal cassette chromosome mec typing showed that four MRSA isolates harbored the type IV cassette, and one type I. In the hemodialysis group, two MRSA isolates were classified as belonging to the USA300-LV genetic lineage. Conversely, in the HIV infected group, no colonizing isolates belonging to the USA300-Latin American Variant (UDA300-LV) lineage were identified. Colonizing isolates recovered from the HIV-infected group belonged to the prevalent hospital-associated clones circulating in Latin America (Chilean [n = 1] and Pediatric [n = 2]). The prevalence of MRSA colonization in the study groups was 3.6% (HIV) and 13.3% (hemodialysis). Surveillance programs should be implemented in this group of patients in order to understand the dynamics of colonization and infection in high-risk patients.