Cell Proliferation and Apoptosis-Key Players in the Lung Aging Process.

Currently, the global lifespan has increased, resulting in a higher proportion of the population over 65 years. Changes that occur in the lung during aging increase the risk of developing acute and chronic lung diseases, such as acute respiratory distress syndrome, chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, and lung cancer. During normal tissue homeostasis, cell proliferation and apoptosis create a dynamic balance that constitutes the physiological cell turnover. In basal conditions, the lungs have a low rate of cell turnover compared to other organs. During aging, changes in the rate of cell turnover in the lung are observed. In this work, we review the literature that evaluates the role of molecules involved in cell proliferation and apoptosis in lung aging and in the development of age-related lung diseases. The list of molecules that regulate cell proliferation, apoptosis, or both processes in lung aging includes TNC, FOXM1, DNA-PKcs, MicroRNAs, BCL-W, BCL-XL, TCF21, p16, NOX4, NRF2, MDM4, RPIA, DHEA, and MMP28. However, despite the studies carried out to date, the complete signaling pathways that regulate cell turnover in lung aging are still unknown. More research is needed to understand the changes that lead to the development of age-related lung diseases.

Identification of the Remains of an Adult Using DNA from Their Deciduous Teeth as a Reference Sample.

In many forensic cases, the identification of human remains is performed by comparing their genetic profile with profiles from reference samples of relatives, usually the parents. Here, we report, for the first time, the identification of the remains of an adult using DNA from the person's deciduous teeth as a reference sample. Fragments of a skeletonized and burned body were found, and a short tandem repeat (STR) profile was obtained. A woman looking for her missing son went to the authorities. When the DNA profile of the woman was compared to a database, a positive match suggested a first-degree kinship with the person to whom the remains belonged. The woman had kept three deciduous molars from her son for more than thirty years. DNA typing of dental pulp was performed. The genetic profiles obtained from the molars and those from the remains coincided in all alleles. The random match probability was 1 in 2.70 × 1021. Thus, the remains were fully identified. In the routine identification of human remains, ambiguous STR results may occur due to the presence of null alleles or other mutational events. In addition, erroneous results can be produced by false matches with close family members or even with people who are completely unrelated to the victim, such that, in some cases, a probability of paternity greater than 99.99% does not necessarily indicate biological paternity. Whenever possible, it is preferable to use reference samples from the putative victim as a source of DNA for identification.

Back to the Basics: Usefulness of Naturally Aged Mouse Models and Immunohistochemical and Quantitative Morphologic Methods in Studying Mechanisms of Lung Aging and Associated Diseases.

Aging-related molecular and cellular alterations in the lung contribute to an increased susceptibility of the elderly to devastating diseases. Although the study of the aging process in the lung may benefit from the use of genetically modified mouse models and omics techniques, these approaches are still not available to most researchers and produce complex results. In this article, we review works that used naturally aged mouse models, together with immunohistochemistry (IHC) and quantitative morphologic (QM) methods in the study of the mechanisms of the aging process in the lung and its most commonly associated disorders: cancer, chronic obstructive pulmonary disease (COPD), and infectious diseases. The advantage of using naturally aged mice is that they present characteristics similar to those observed in human aging. The advantage of using IHC and QM methods lies in their simplicity, economic accessibility, and easy interpretation, in addition to the fact that they provide extremely important information. The study of the aging process in the lung and its associated diseases could allow the design of appropriate therapeutic strategies, which is extremely important considering that life expectancy and the number of elderly people continue to increase considerably worldwide.

Nestin-Expressing Cells in the Lung: The Bad and the Good Parts.

Nestin is a member of the intermediate filament family, which is expressed in a variety of stem or progenitor cells as well as in several types of malignancies. Nestin might be involved in tissue homeostasis or repair, but its expression has also been associated with processes that lead to a poor prognosis in various types of cancer. In this article, we review the literature related to the effect of nestin expression in the lung. According to most of the reports in the literature, nestin expression in lung cancer leads to an aggressive phenotype and resistance to chemotherapy as well as radiation treatments due to the upregulation of phenomena such as cell proliferation, angiogenesis, and metastasis. Furthermore, nestin may be involved in the pathogenesis of some non-cancer-related lung diseases. On the other hand, evidence also indicates that nestin-positive cells may have a role in lung homeostasis and be capable of generating various types of lung tissues. More research is necessary to establish the true value of nestin expression as a prognostic factor and therapeutic target in lung cancer in addition to its usefulness in therapeutic approaches for pulmonary diseases.

Schwann Cell Precursor Transplant in a Rat Spinal Cord Injury Model.

BACKGROUND: Differentiation of mesenchymal stem cells into Schwann cell precursors could reverse established lesions and sequelae of medullary transection. OBJECTIVE: The objective of this study was to study the clinical response of mesenchymal stem cell transplantation with Schwann precursor cell transplantation in a rat spinal cord injury model, using motor function and histopathologic studies. MATERIALS AND METHODS: A total of 28 Sprague-Dawley rats were randomly divided among four groups (n = 7 in each): sham group, control group, mesenchymal stem cell transplant group, and Schwann cell precursor transplant group. The surgical procedure was a laminectomy with transection of the spinal cord at the T11 level in the transplant groups and the injury control group. After 1 week, the transplant groups received stem cells directly in the injury site. Hind limb motor function was assessed using the locomotive scale of Basso, Beattie, and Bresnahan. 1 month after transplantation, all specimens were sacrificed to make a histopathologic description of sections taken from the site of injury and where stem cells were transplanted. Mean scores of mobility were compared using analysis of variance (ANOVA) of one factor with 95% reliability between groups and ANOVA of repetitive measures to evaluate evolution in the same group. RESULTS: We observed that the control group had statistically greater mobility than the other groups (p < 0.0001) and that the group with spinal injury without treatment had the lowest mean mobility. The mobility score values from the Schwann cell precursor group were statistically higher than the group treated with mesenchymal stem cells (p < 0.0001). CONCLUSION: Schwann precursor cells had a greater effect on locomotive function than mesenchymal stem cells.

Analysis of Cell Turnover in the Bronchiolar Epithelium Through the Normal Aging Process.

PURPOSE: Aging is associated with changes in the lung that leads to a decrease in its function. Alterations in structure and function in the small airways are well recognized in chronic lung diseases. The aim of this study was the assessment of cell turnover in the bronchiolar epithelium of mouse through the normal aging process. METHODS: Lungs from CD1 mice at the age of 2, 6, 12, 18, or 24 months were fixed in neutral-buffered formalin and paraffin-embedded. Proliferating cell nuclear antigen was examined by immunohistochemistry. Apoptosis was analyzed by in situ end-labeling of fragmented DNA. Epithelial dimensions were analyzed by morphometry. RESULTS: The 2-month-old mice showed significantly higher number of proliferating cells when compared with mice at all other age groups. The number of apoptotic cells in mice at 24 months of age was significantly greater than in mice at all other age groups. Thus, the number of epithelial cells decreased as the age of the subject increased. We also found reductions in both area and height of the bronchiolar epithelium in mice at 18 and 24 months of age. CONCLUSIONS: We found a decrease in the total number of epithelial cells in the aged mice, which was accompanied by a thinning of the epithelium. These changes reflect a dysregulated tissue regeneration process in the bronchiolar epithelium that might predispose to respiratory diseases in elderly subjects.

The unique effects of environmental strategies in health promotion campaigns: a review.

Various strategies are used as tools in health promotion campaigns to increase health-related outcomes among target populations. Evaluations of these campaigns examine effects on changing people's knowledge, attitudes, and/or behaviors. Most evaluations examine the combined impact of multiple strategies. Less is known about the unique effects of particular strategies. To address this gap, we used highly systematic methods to identify and review scientifically rigorous evaluations of 18 campaigns that examined the unique effects of three sets of intervention strategies (entertainment education, law enforcement, and mass media) on changes in knowledge, attitudes, and practice with regard to various health behaviors. Results showed differences in evaluation processes based on the type of strategy used to promote campaign messages. For instance, evaluations of mass-media based campaigns were more likely to examine changes in knowledge, relative to evaluations of campaigns that used law enforcement strategies. In addition, campaign effects varied by particular strategies. Mass media-based campaigns were more likely to affect knowledge, relative to behaviors. Law enforcement and entertainment education-based campaigns showed positive effects on behaviors. The implications for planning and evaluating health promotion campaigns are described.

Genetic factors play an important role in the pathogenesis of hyperlipidemia post-transplantation.

BACKGROUND: Our purpose was to identify factors associated with hyperlipidemia post-transplantation in a Hispanic population. METHODS: From 1985 to 1999, a kidney graft survival longer than 3 months occurred in 293 cases at the Instituto Nacional de la Nutrición. Most of the patients living in Mexico City were included (n = 83). The evaluation included a questionnaire, blood samples, and assessment of body composition and dietary habits. As many as possible first-degree relatives were studied. RESULTS: Women had higher values of cholesterol (236 +/- 51 versus 215 +/-41; P < 0.05), low-density lipoprotein cholesterol (147 +/- 42 versus 131 +/- 34; P = 0.05), high-density lipoprotein cholesterol (57.3 +/- 14 versus 47.9 +/- 14; P = 0.002) and high-density lipoprotein-2 cholesterol. Isolated hypercholesterolemia was the most common lipid abnormality (40.9%), followed by mixed hyperlipidemia. Lipoprotein (a) greater than 30 mg/dL was found in 13 cases. Familial combined hyperlipidemia (FCHL) in the patient's relatives was a marker for dyslipidemia (odds ratio, 7.04; 95% confidence interval, 1.2 to 59.7). These cases had a worse lipid profile. Cyclosporine-treated FCHL patients had higher lipid levels compared with the non-FCHL, cyclosporine-treated patients. The effects of cyclosporine on the lipid levels were lower, but significant, after the exclusion of the FCHL cases. CONCLUSION: Post-transplant dyslipidemia is determined by genetic and environmental factors. FCHL in the patient's relatives was associated with post-transplant hyperlipidemia; an additive effect with cyclosporine was found. The evaluation of the lipid profile of relatives may be useful for the assessment of the risk of post-transplant dyslipidemia.

Study of the complexation behavior of tenoxicam with cyclodextrins in solution: improved solubility and percutaneous permeability.

Complexation of tenoxicam (TEN) with gamma-, HPgamma-, beta,-, HPbeta-, and Mbeta-cyclodextrin (CD) in aqueous solution at pH 7.4 has been investigated using phase solubility diagrams. TEN formed soluble complexes with 1:1 stoichiometry with all the CDs studied, although the inclusion stability constants (K1:1) obtained had low values. The presence of propylene glycol (PG) in the dissolution medium decreased the stability constants and led to a higher fraction of free drug by competitive displacement and by an increase in the lipophility of the media. Among the CDs tested, MbetaCD was chosen for further studies since TEN-MbetaCD complexes yielded the best results: good solubility and the highest stability constant. The effect of MbetaCD and PG on the TENpartitioning coefficient was also studied in skin-buffer systems. Although each substance reduced the partitioning value, the combination of PG and MbetaCD increased this parameter. The noticeable increase in solubility of the drug found in the presence of MbetaCD allowed the formulation of carbopol gels with higher doses of TEN and a reduced amount of cosolvent. The presence of MbetaCD improved the percutaneous penetration of TEN through abdominal rat skin by increasing the solubility of the drug in the vehicle and by affecting the partitioning behavior of TEN in the skin. In addition, TEN retention in the skin was found to be related to the flux values attained with the corresponding gels.