Morphological and functional changes in the rabbit iris and ciliary body in experimental hypopinealism

Background: Previous morphological studies have found degenerative retinal abnormalities in experimental hypopinealism. It is important to determine the morphology and function of the iris and ciliary body in prolonged pineal gland dysfunction with melatonin deficiency. Purpose: To determine the morphology and function of the iris and ciliary body in rabbits maintained under conditions of prolonged around-the-clock illumination leading to hypopinealism and melatonin deficiency. Material and Methods: Fifty five adult rabbits (110 eyes) were used in this experimental study. Animals were divided into two groups, an experimental group of 32 animals maintained under conditions of around-the-clock illumination to induce functional hypopinealism, and a control group of 23 animals maintained under natural day/night cycle conditions. Both groups were subdivided into 5 subgroups based on the duration of the experiment: 1-2 months, 3-5 months, 8-12 months, 18-19 months, and) 26-28 months. Blood melatonin levels were assessed by an enzyme-linked immunosorbent assay. A comprehensive morphological study of rabbit iris and ciliary body specimens was conducted. Results. Blood melatonin level at night time in the experimental group was almost six-fold lower than blood melatonin level in the control group. In animals maintained under conditions of around-the-clock illumination, marked circulatory abnormalities with markedly dilated and hyperemic vessels were observed in the iris and ciliary body at time points until 12 months. In addition, at 12 to 28 months, iris and ciliary body vascular circulatory abnormalities appeared to be changed by sclerotic abnormalities. In animals exposed to around-the-clock illumination, vascular sclerotic changes appeared substantially earlier, and were much more marked, than in control animals. The mean vascular wall thickness (VWT) in iris and ciliary body specimens for the experimental group was 1.5-fold higher than that for the control group (177.5 ± 7.3×10-6 m vs 101.9 ± 4.4×10-6; р < 0.05) at 18 to 19 months, and twice higher than that for the control group (217.4 ± 8.7×10-6 m vs 107.2 ± 5.2 ×10-6 m) at 26 to 28 months. The like newly formed rough bundles of collagen fibers found in an analogue of the Schlemm canal may exert a very negative effect on hydrodynamics of the eye

ВЕРОЯТНОСТНЫЕ ХАРАКТЕРИСТИКИ СУБПРОЦЕССОВ В ТЛЕЮЩЕМ РАЗРЯДЕ

As a result of analyzing experimental data, analytical expressions were developed for calculating the probabilistic characteristics of the most tangible subprocesses during nitriding in a glow discharge.Приведены аналитические выражения для расчета вероятностных характеристик наиболее весомых субпроцессов при азотировании в тлеющем разряде, полученные на основе результатов обработки экспериментальных данных

Oxidative DNA damage in lung tissue from patients with COPD is clustered in functionally significant sequences

Lung tissue from COPD patients displays oxidative DNA damage. The present study determined whether oxidative DNA damage was randomly distributed or whether it was localized in specific sequences in either the nuclear or mitochondrial genomes. The DNA damage-specific histone, gamma-H2AX, was detected immunohistochemically in alveolar wall cells in lung tissue from COPD patients but not control subjects. A PCR-based method was used to search for oxidized purine base products in selected 200 bp sequences in promoters and coding regions of the VEGF, TGF-β1, HO-1, Egr1, and β-actin genes while quantitative Southern blot analysis was used to detect oxidative damage to the mitochondrial genome in lung tissue from control subjects and COPD patients. Among the nuclear genes examined, oxidative damage was detected in only 1 sequence in lung tissue from COPD patients: the hypoxic response element (HRE) of the VEGF promoter. The content of VEGF mRNA also was reduced in COPD lung tissue. Mitochondrial DNA content was unaltered in COPD lung tissue, but there was a substantial increase in mitochondrial DNA strand breaks and/or abasic sites. These findings show that oxidative DNA damage in COPD lungs is prominent in the HRE of the VEGF promoter and in the mitochondrial genome and raise the intriguing possibility that genome and sequence-specific oxidative DNA damage could contribute to transcriptional dysregulation and cell fate decisions in COPD

P21-PARP-1 pathway is involved in cigarette smoke-induced lung DNA damage and cellular senescence

Persistent DNA damage triggers cellular senescence, which may play an important role in the pathogenesis of cigarette smoke (CS)-induced lung diseases. Both p21(CDKN1A) (p21) and poly(ADP-ribose) polymerase-1 (PARP-1) are involved in DNA damage and repair. However, the role of p21-PARP-1 axis in regulating CS-induced lung DNA damage and cellular senescence remains unknown. We hypothesized that CS causes DNA damage and cellular senescence through a p21-PARP-1 axis. To test this hypothesis, we determined the levels of γH2AX (a marker for DNA double-strand breaks) as well as non-homologous end joining proteins (Ku70 and Ku80) in lungs of mice exposed to CS. We found that the level of γH2AX was increased, whereas the level of Ku70 was reduced in lungs of CS-exposed mice. Furthermore, p21 deletion reduced the level of γH2AX, but augmented the levels of Ku70, Ku80, and PAR in lungs by CS. Administration of PARP-1 inhibitor 3-aminobenzamide increased CS-induced DNA damage, but lowered the levels of Ku70 and Ku80, in lungs of p21 knockout mice. Moreover, 3-aminobenzamide increased senescence-associated β-galactosidase activity, but decreased the expression of proliferating cell nuclear antigen in mouse lungs in response to CS. Interestingly, 3-aminobenzamide treatment had no effect on neutrophil influx into bronchoalveolar lavage fluid by CS. These results demonstrate that the p21-PARP-1 pathway is involved in CS-induced DNA damage and cellular senescence

Probabilistic Characteristics of Subprocesses in a Glow Discharge

As a result of analyzing experimental data, analytical expressions were developed for calculating the probabilistic characteristics of the most tangible subprocesses during nitriding in a glow discharge

Probabilistic characteristics of subprocesses in a glow discharge

Приведены аналитические выражения для расчета вероятностных характеристик наиболее весомых субпроцессов при азотировании в тлеющем разряде, полученные на основе результатов обработки экспериментальных данных.As a result of analyzing experimental data, analytical expressions were developed for calculating the probabilistic characteristics of the most tangible subprocesses during nitriding in a glow discharge

Probabilistic characteristics of subprocesses in a glow discharge

Приведены аналитические выражения для расчета вероятностных характеристик наиболее весомых субпроцессов при азотировании в тлеющем разряде, полученные на основе результатов обработки экспериментальных данных.As a result of analyzing experimental data, analytical expressions were developed for calculating the probabilistic characteristics of the most tangible subprocesses during nitriding in a glow discharge