Using the Gompertz-Strehler model of aging and mortality to explain mortality trends in industrialized countries.

Mortality trends in industrialized countries are characterized by declines in vascular disease (ischemic heart disease and stroke) and rises in cancers and degenerative diseases. These trends are typically analyzed by examining each disorder in isolation using the perspective of genetic and environmental influences. However, longitudinal Gompertzian analysis and the Gompertz-Strehler model of aging and mortality as modified by Lestienne suggest that age-specific mortality rates, for both general and disease-specific mortality, are an interrelated deterministic function of aggregate genetic, environmental and competitive influences. Consequently, evolving mortality trends and patterns appear to be influenced by three factors (with deterministic competition being the third factor), rather than just two factors (genetic and environmental) as commonly depicted.     

Comparison of the Staph-Ident System with a Conventional Method for Species Identification of Urine and Blood Isolates of Coagulase-Negative Staphylococci

The Staph-Ident system (Analytab Products) for species identification of coagulase-negative staphylococci was compared with the conventional method of Kloos and Schleifer (21). A total of 101 clinical isolates from urine cultures and 95 clinical isolates from blood cultures were studied: overall agreement between the two methods was 86%. We concluded that the Staph-Ident system is a practical test for most clinical microbiology laboratories and that results obtained from this rapid test are comparable to those obtained from the more cumbersome conventional method. Additional investigations are needed to determine the clinical relevance of such species identification.     

Exposure of brown Norway rats to diesel exhaust particles prior to ovalbumin (OVA) sensitization elicits IgE adjuvant activity but attenuates OVA-induced airway inflammation.

Exposure to diesel exhaust particles (DEP) during the sensitization process has been shown to increase antigen-specific IgE production and aggravate allergic airway inflammation in human and animal models. In this study, we evaluated the effect of short-term DEP exposure on ovalbumin (OVA)-mediated responses using a post-sensitization model. Brown Norway rats were first exposed to filtered air or DEP (20.6 +/- 2.7 mg/m3) for 4 h/day for five consecutive days. One day after the final air or DEP exposure (day 1), rats were sensitized with aerosolized OVA (40.5 +/- 6.3 mg/m3), and then again on days 8 and 15, challenged with OVA on day 29, and sacrificed on days 9 or 30, 24 h after the second OVA exposure or the final OVA challenge, respectively. Control animals received aerosolized saline instead of OVA. DEP were shown to elicit an adjuvant effect on the production of antigen-specific IgE and IgG on day 30. At both time points, no significant airway inflammatory responses and lung injury were found for DEP exposure alone. However, the OVA-induced inflammatory cell infiltration, acellular lactate dehydrogenase activity and albumin content in bronchoalveolar lavage (BAL) fluid, and numbers of T cells and their CD4+ and CD8+ subsets in lung-draining lymph nodes were markedly reduced by DEP on day 30 compared with the air-plus-OVA exposure group. The OVA-induced nitric oxide (NO) in the BAL fluid and production of NO, interleukin (IL)-10, and IL-12 by alveolar macrophages (AM) were also significantly lowered by DEP on day 30 as well as day 9. DEP or OVA alone decreased intracellular glutathione (GSH) in AM and lymphocytes on days 9 and 30. The combined DEP and OVA exposure resulted in further depletion of GSH in both cell types. These results show that short-term DEP exposure prior to sensitization had a delayed effect on enhancement of the sensitization in terms of allergen-specific IgE and IgG production, but caused an attenuation of the allergen-induced airway inflammatory responses.     

Vitamin D,folate, and potential early lifecycle environmental origin of significant adult phenotypes

Background and objectives: Vitamin D and folate are highly UV sensitive, and critical for maintaining health throughout the lifecycle. This study examines whether solar irradiance during the first trimester of pregnancy influences vitamin D receptor (VDR) and nuclear folate gene variant occurrence, and whether affected genes influence late-life biochemical/clinical phenotypes.Methodology: 228 subjects were examined for periconceptional exposure to solar irradiance, variation in vitamin D/folate genes (polymerase chain reaction (PCR)), dietary intake (food frequency questionnaire (FFQ)) and important adult biochemical/clinical phenotypes.Results: Periconceptional solar irradiance was associated with VDR-BsmI (P = 0.0008^wk7), TaqI (P = 0.0014^wk7) and EcoRV (P = 0.0030^wk6) variant occurrence between post-conceptional weeks 6–8, a period when ossification begins. Similar effects were detected for other VDR gene polymorphisms. Periconceptional solar irradiance was also associated with 19 bp del-DHFR (P = 0.0025^wk6), and to a lesser extent C1420T-SHMT (P = 0.0249^wk6), a folate-critical time during embryogenesis. These same genes were associated with several late-life phenotypes: VDR-BsmI, TaqI and ApaI determined the relationship between dietary vitamin D and both insulin (P < 0.0001/BB, 0.0007/tt and 0.0173/AA, respectively) and systolic blood pressure (P = 0.0290/Bb, 0.0299/Tt and 0.0412/AA, respectively), making them important early and late in the lifecycle. While these and other phenotype associations were found for the VDR variants, folate polymorphism associations in later-life were limited to C1420T-SHMT (P = 0.0037 and 0.0297 for fasting blood glucose and HbA1c levels, respectively). We additionally report nutrient–gene relationships with body mass index, thiol/folate metabolome, cognition, depression and hypertension. Furthermore, photoperiod at conception influenced occurrence of VDR-Tru9I and 2R3R-TS genotypes (P = 0.0120 and 0.0360, respectively).Conclusions and implications: Findings identify environmental and nutritional agents that may interact to modify gene–phenotype relationships across the lifecycle, offering new insight into human ecology. This includes factors related to both disease aetiology and the evolution of skin pigmentation.     

A comparative study of three methods of nasal irrigation

OBJECTIVE: To assess the effectiveness of three methods of nasal irrigation on distributing saline to the nasal cavity and paranasal sinuses. DESIGN:: A prospective, cross-over study. MATERIALS AND METHODS: Twelve subjects (9 patients with chronic sinusitis after functional endoscopic sinus surgery and 3 healthy controls) underwent nasal irrigation with normal saline containing Technetium 99m sulfur colloid. The distribution of radioactivity was assessed on each subject after three different irrigation techniques: metered nasal spray, nebulization with RinoFlow, and nasal douching while kneeling with the head on the floor. RESULTS: The nasal cavity was well irrigated by all three techniques. Compared with the other two methods, douching was significantly more effective in penetrating the maxillary sinus (P = .036) and frontal recess (P = .003). The sphenoid and frontal sinuses were poorly irrigated by all three techniques. CONCLUSION: Nasal douches are more effective in distributing irrigation solution to the maxillary sinus and frontal recess. This should be the method of choice for irrigating these areas.     

Hyperosmolar solution effects in guinea pig airways. IV. Lipopolysaccharide-induced alterations in airway reactivity and epithelial bioelectric responses to methacholine and hyperosmolarity

We investigated the in vivo and in vitro effects of lipopolysaccharide (LPS) treatment (4 mg/kg i.p.) on guinea pig airway smooth muscle reactivity and epithelial bioelectric responses to methacholine (MCh) and hyperosmolarity. Hyperosmolar challenge of the epithelium releases epithelium-derived relaxing factor (EpDRF). Using a two-chamber, whole body plethysmograph 18 h post-treatment, animals treated with LPS were hyporeactive to inhaled MCh aerosol. This could involve an increase in the release and/or actions of EpDRF, because LPS treatment enhanced EpDRF-induced smooth muscle relaxation in vitro in the isolated perfused trachea apparatus. In isolated perfused tracheas the basal transepithelial potential difference (Vt) was increased after LPS treatment. The increase in Vt was inhibited by amiloride and indomethacin. Concentration-response curves for changes in Vt in response to serosally and mucosally applied MCh were biphasic (hyperpolarization, <3 x 10(-7)M; depolarization, >3 x 10(-7)M); MCh was more potent when applied serosally. The hyperpolarization response to MCh, but not the depolarization response, was potentiated after LPS treatment. In both treatment groups, mucosally applied hyperosmolar solution (using added NaCl) depolarized the epithelium; this response was greater in tracheas from LPS-treated animals. The results of this study indicate that airway hyporeactivity in vivo after LPS treatment is accompanied by an increase in the release and/or actions of EpDRF in vitro. These changes may involve LPS-induced bioelectric alterations in the epithelium.     

Suppression in lung defense responses after bacterial infection in rats pretreated with different welding fumes

Epidemiology suggests that inhalation of welding fumes increases the susceptibility to lung infection. The effects of chemically distinct welding fumes on lung defense responses after bacterial infection were compared. Fume was collected during gas metal arc (GMA) or flux-covered manual metal arc (MMA) welding using two consumable electrodes: stainless steel (SS) or mild steel (MS). The fumes were separated into water-soluble and -insoluble fractions. The GMA-SS and GMA-MS fumes were found to be relatively insoluble, whereas the MMA-SS was highly water soluble, with the soluble fraction comprised of 87% Cr and 11% Mn. On day 0, male Sprague-Dawley rats were intratracheally instilled with saline (vehicle control) or the different welding fumes (0.1 or 2 mg/rat). At day 3, the rats were intratracheally inoculated with 5 x 10(3) Listeria monocytogenes. On days 6, 8, and 10, left lungs were removed, homogenized, cultured overnight, and colony-forming units were counted to assess pulmonary bacterial clearance. Bronchoalveolar lavage (BAL) was performed on right lungs to recover phagocytes and BAL fluid to measure the production of nitric oxide (NO) and immunomodulatory cytokines, including tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-2, IL-6, and IL-10. In contrast to the GMA-SS, GMA-MS, and saline groups, pretreatment with the highly water soluble MMA-SS fume caused significant body weight loss, extensive lung damage, and a dramatic reduction in pulmonary clearance of L. monocytogenes after infection. NO concentrations in BAL fluid and lung immunostaining of inducible NO synthase were dramatically increased in rats pretreated with MMA-SS before and after infection. MMA-SS treatment caused a significant decrease in IL-2 and significant increases in TNF-alpha, IL-6, and IL-10 after infection. In conclusion, pretreatment with MMA-SS increased production of NO and proinflammatory cytokines (TNF-alpha and IL-6) after infection, which are likely responsible for the elevation in lung inflammation and injury. In addition, MMA-SS treatment reduced IL-2 (involved in T cell proliferation) and enhanced IL-10 (involved in inhibiting macrophage function) after bacterial infection, which might result in a possible suppression in immune response and an increase in susceptibility to infection.     

Do tumor necrosis factor inhibitors cause uveitis? A registry-based study

OBJECTIVE: Population-based studies of patients with ankylosing spondylitis indicate that tumor necrosis factor (TNF) inhibitors prevent uveitis. Paradoxically, anecdotal reports implicate etanercept as a cause of uveitis. Therefore, using the information from 2 drug events databases, the purpose of this study was to assess reported cases of uveitis associated with the use of TNF inhibitors. METHODS: Uveitis cases occurring in the US associated with etanercept, infliximab, or adalimumab therapy that were reported to 2 spontaneous reporting databases prior to January 1, 2006 were reviewed. RESULTS: Overall, there were 43 cases of uveitis associated with etanercept, 14 associated with infliximab, and 2 associated with adalimumab. After normalizing for the estimated number of patients treated with each medication, etanercept was associated with a greater number of uveitis cases than infliximab (P < 0.001) and adalimumab (P < 0.01), while no such association was found between adalimumab and infliximab (P > 0.5). Using a priori criteria to avoid including patients whose underlying disease was associated with uveitis, 20 cases associated with etanercept, 4 cases associated with infliximab, and 2 cases associated with adalimumab were identified. A repeat analysis again revealed a greater number of uveitis cases associated with etanercept (P < 0.001 versus infliximab). CONCLUSION: Etanercept therapy is associated with a significantly greater number of reported uveitis cases in comparison with infliximab and adalimumab in 2 medication side effect registries. These results are consistent with previous studies and suggest that this relationship is drug specific and not related to TNF inhibitors as a whole. However, our findings do not support the use of infliximab over etanercept; rather, if a patient develops uveitis during etanercept therapy, then a change to infliximab may be warranted.