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1.
Genes (Basel) ; 14(2)2023 02 10.
Article in English | MEDLINE | ID: mdl-36833388

ABSTRACT

Non-small cell lung cancer (NSCLC) accounts for the vast majority of cases of lung neoplasms. It is formed in multiple stages, with interactions between environmental risk factors and individual genetic susceptibility and with genes involved in the immune and inflammatory response paths, cell or genome stability, and metabolism, among others. Our objective was to evaluate the association between five genetic variants (IL-1A, NFKB1, PAR1, TP53, and UCP2) and the development of NSCLC in the Brazilian Amazon. The study included 263 individuals with and without lung cancer. The samples were analyzed for the genetic variants of NFKB1 (rs28362491), PAR1 (rs11267092), TP53 (rs17878362), IL-1A (rs3783553), and UCP2 (INDEL 45-bp), which were genotyped in PCR, followed by an analysis of the fragments, in which we applied a previously developed set of informative ancestral markers. We used a logistic regression model to identify differences in the allele and the genotypic frequencies among individuals and their association with NSCLC. The variables of gender, age, and smoking were controlled in the multivariate analysis to prevent confusion by association. The individuals that were homozygous for the Del/Del of polymorphism NFKB1 (rs28362491) (p = 0.018; OR = 0.332) demonstrate a significant association with NSCLC, which was similar to that observed in the variants of PAR1 (rs11267092) (p = 0.023; OR = 0.471) and TP53 (rs17878362) (p = 0.041; OR = 0.510). Moreover, the individuals with the Ins/Ins genotype of polymorphism IL-1A (rs3783553) demonstrated greater risk for NSCLC (p = 0.033; OR = 2.002), as did the volunteers with the Del/Del of UCP2 (INDEL 45-bp) (p = 0.031; OR = 2.031). The five polymorphisms investigated can contribute towards NSCLC susceptibility in the population of the Brazilian Amazon.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , NF-kappa B p50 Subunit , Receptor, PAR-1 , Tumor Suppressor Protein p53 , Uncoupling Protein 2 , Humans , Brazil/epidemiology , NF-kappa B p50 Subunit/genetics , Polymorphism, Genetic , Receptor, PAR-1/genetics , Tumor Suppressor Protein p53/genetics
2.
Genes (Basel) ; 13(4)2022 03 29.
Article in English | MEDLINE | ID: mdl-35456416

ABSTRACT

In Brazil, Acute lymphoid leukemia (ALL) is the leading cause of cancer deaths in children and adolescents. Treatment toxicity is one of the reasons for stopping chemotherapy. Amerindian genomic ancestry is an important factor for this event due to fluctuations in frequencies of genetic variants, as in the NUDT15 and SLC22A1 genes, which make up the pharmacokinetic and pharmacodynamic pathways of chemotherapy. This study aimed to investigate possible associations between NUDT15 (rs1272632214) and SLC22A1 (rs202220802) gene polymorphism and genomic ancestry as a risk of treatment toxicities in patients with childhood ALL in the Amazon region of Brazil. The studied population consisted of 51 patients with a recent diagnosis of ALL when experiencing induction therapy relative to the BFM 2009 protocol. Our results evidenced a significant association of risk of severe infectious toxicity for the variant of the SLC22A1 gene (OR: 3.18, p = 0.031). Genetic ancestry analyses demonstrated that patients who had a high contribution of African ancestry had a significant protective effect for the development of toxicity (OR: 0.174; p = 0.010), possibly due to risk effects of the Amerindian contribution. Our results indicate that mixed populations with a high degree of African ancestry have a lower risk of developing general toxicity during induction therapy for ALL. In addition, individuals with the SLC22A1 variant have a higher risk of developing severe infectious toxicity while undergoing the same therapy.


Subject(s)
Organic Cation Transporter 1 , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Adolescent , Black People , Child , Humans , Organic Cation Transporter 1/genetics , Polymorphism, Genetic , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics , Pyrophosphatases/genetics
3.
Genes (Basel) ; 13(3)2022 03 11.
Article in English | MEDLINE | ID: mdl-35328047

ABSTRACT

Lung cancer is one of the most frequent neoplasms in the world. Because it is a complex disease, its formation occurs in several stages, stemming from interactions between environmental risk factors, such as smoking, and individual genetic susceptibility. Our objective was to investigate associations between a UGT1A1 gene polymorphism (rs8175347) and lung cancer risk in an Amazonian population. This is a pilot study, case-controlled study, which included 276 individuals with cancer and without cancer. The samples were analyzed for polymorphisms of the UGT1A1 gene (rs8175347) and genotyped in PCR, followed by fragment analysis in which we applied a previously developed set of informative ancestral markers. We used logistic regression to identify differences in allelic and genotypic frequencies between individuals. Individuals with the TA7 allele have an increased chance of developing lung adenocarcinoma (p = 0.035; OR: 2.57), as well as those with related genotypes of reduced or low enzymatic activity: TA6/7, TA5/7, and TA7/7 (p = 0.048; OR: 8.41). Individuals with homozygous TA7/7 have an increased chance of developing squamous cell carcinoma of the lung (p = 0.015; OR: 4.08). Polymorphism in the UGT1A1 gene (rs8175347) may contribute as a risk factor for adenocarcinoma and lung squamous cell carcinoma in the population of the Amazon region.


Subject(s)
Carcinoma, Squamous Cell , Glucuronosyltransferase , Lung Neoplasms , Glucuronosyltransferase/genetics , Humans , Lung Neoplasms/genetics , Pilot Projects , Polymorphism, Genetic , Risk Factors
4.
Genes (Basel) ; 14(1)2022 12 24.
Article in English | MEDLINE | ID: mdl-36672804

ABSTRACT

Gastric cancer (GC) is a multifactorial, complex, and aggressive disease with a prevalence of one million new cases and high global mortality. Factors such as genetic, epigenetic, and environmental changes contribute to the onset and progression of the disease. Identification of INDELs in miRNA and its target sites in current studies showed an important role in the development of cancer. In GC, miRNAs act as oncogenes or tumor suppressors, favoring important cancer pathways, such as cell proliferation and migration. This work aims to investigate INDELs in the coding region of miRNAs (hsa-miR-302c, hsa-miR-548AJ-2, hsa-miR-4274, hsa-miR-630, hsa-miR-516B-2, hsa-miR-4463, hsa-miR-3945, hsa-miR-548H_4, hsa-miR-920, has-mir-3171, and hsa-miR-3652) that may be associated with susceptibility and clinical variants of gastric cancer. For this study, 301 patients with GC and 145 individuals from the control group were selected from an admixed population in the Brazilian Amazon. The results showed the hsa-miR-4463, hsa-miR-3945, hsa-miR-548H_4, hsa-miR-920 and hsa-miR-3652 variants were associated with gastric cancer susceptibility. The hsa-miR-4463 was significantly associated with clinical features of GC such as diffuse gastric tumor histological type, "non-cardia" localization region, and early onset. Our findings indicated that INDELs could be potentially functional genetic variants for gastric cancer risk.


Subject(s)
MicroRNAs , Stomach Neoplasms , Humans , Stomach Neoplasms/pathology , Gene Expression Regulation, Neoplastic , MicroRNAs/genetics , MicroRNAs/metabolism , Oncogenes , Biomarkers, Tumor/genetics
5.
J Pers Med ; 11(10)2021 Oct 19.
Article in English | MEDLINE | ID: mdl-34683186

ABSTRACT

BACKGROUND: Sarcopenia is a disease characterized by progressive reduction in muscle mass and strength or function. Although it is known that sarcopenia may be associated with environmental factors, studies suggest the identification of genes related to skeletal muscle maintenance that explain the susceptibility to the disease. OBJECTIVE: To analyze the influence of NFkB1 gene polymorphism on susceptibility to sarcopenia in the elderly. METHODS: This is a case-control study, which included 219 elderly people, 74 elderly people with sarcopenia, and 145 without sarcopenia. Samples were analyzed for NFkB1 gene polymorphism (rs28362491), genotyped in PCR, and followed by fragment analysis. To avoid misinterpretation due to population substructure, we applied a previously developed set of 61 informative ancestral markers that were genotyped by multiplex PCR. We used logistic regression to identify differences in genotypic frequencies between elderly people with and without sarcopenia. RESULTS: It was observed that the NFkB1 gene polymorphism presented frequencies of 24%, 50%, and 26% for the genotype DEL/DEL, DEL/INS, and INS/INS, respectively. Furthermore, elderly individuals with the INS/INS genotype had increased chances (p = 0.010; OR:2.943; 95%CI:1.301-6.654) for the development of sarcopenia. CONCLUSION: The INDEL polymorphism of the NFkB1 gene (rs28362491) may influence the susceptibility to sarcopenia in the elderly in elderly people in the Amazon.

6.
Am J Transl Res ; 12(7): 4043-4050, 2020.
Article in English | MEDLINE | ID: mdl-32774757

ABSTRACT

It is known that abnormal expression of miRNAs in the gastric cancer (GC) contributes to its carcinogenesis. Therefore, ingestion of commercial (usual) water on a daily basis may be a contributing factor for the occurrence of alterations in the gastric mucosal. In this study, it was evaluated the expression of the miRNAs miR-29c, miR-7, miR-155, and miR-135b in the gastric tissue of patients with gastritis before and after the consumption of alkaline water (pH range from 8.0 to 10.0), as well as the clinic pathological characteristics. METHODS: 50 subjects from the Amazon region, diagnosed with gastritis that routinely used commercial (usual) water with a pH lower than 5.0, were enrolled to change the consume water to a pH of 8.5 to 10.0 for 5 months. RESULTS: Endoscopic findings of gastritis were such different (less severe disease), P = 0.024; in 43% diagnosed with moderate gastritis upfront esophagogastroduodenoscopy (EGD) presented mild gastritis after the consumption of alkaline water, according to study methods; there were no worsening gastritis and there were a significant increase in the expression of miR-135b (P = 0.039) and miR-29c (P = 0.039). CONCLUSION: Modified pH range water (from 8.0 to 10.0) ingested for 5 months was able lead to a less severe gastritis according to the Sidney classification system, suggesting that this lifestyle change represented a clinical benefit in patients with gastritis on the Amazon region. In addition, higher expression of miR-135b and miR-29c was observed after the consumption of alkaline water for 5 months.

7.
Insects ; 12(1)2020 Dec 29.
Article in English | MEDLINE | ID: mdl-33383724

ABSTRACT

Spodoptera frugiperda was first reported in Africa in 2016 and has since become a serious threat to maize/cereal production on the continent. Current control of the pest relies on synthetic chemical insecticides, which can negatively impact the environment and promote the development of resistance when used indiscriminately. Therefore, great attention is being paid to the development of safer alternatives. In this study, several biorational products and a semi-synthetic insecticide were evaluated. Two household soaps ("Palmida" and "Koto") and a detergent ("So Klin") were first tested for their efficacy against the larvae under laboratory conditions. Then, the efficacy of the most effective soap was evaluated in field conditions, along with PlantNeem (neem oil), Dezone (diatomaceous earth), and Emacot 19 EC (emamectin benzoate), in two districts, N'Dali and Adjohoun, located, respectively, in northern and southern Benin. The soaps and the detergent were highly toxic t second-instar larvae with 24 h lethal concentrations (LC50) of 0.46%, 0.44%, and 0.37% for So Klin, Koto, and Palmida, respectively. In field conditions, the biorational insecticides produced similar or better control than Emacot 19 EC. However, the highest maize grain yields of 7387 and 5308 kg/ha were recorded, respectively, with Dezone (N'Dali) and Emacot 19 EC (Adjohoun). A cost-benefit analysis showed that, compared to an untreated control, profits increased by up to 90% with the biorational insecticides and 166% with Emacot 19 EC. Therefore, the use of Palmida soap at 0.5% concentration, neem oil at 4.5 L/ha, and Dezone at 7.5 kg/ha could provide an effective, environmentally friendly, and sustainable management of S. frugiperda in maize.

8.
Plant Biol (Stuttg) ; 22(1): 55-61, 2020 Jan.
Article in English | MEDLINE | ID: mdl-31550071

ABSTRACT

Frost events occur with a significant frequency in savannas of the Southern Hemisphere, especially in the Cerrados of Brazil. One of the main strategies to deal with such events is to invest in thick and dense bark, which can insulate internal branch tissues and protect buds, essential to ensure resprouting if frost damage causes plant canopy die-back. Such strategies may be fundamental to determine the persistence of savanna species in regions where low temperatures and frost events are recurrent. Here we describe bud protection and bark strategies of 53 woody species growing in typical savanna vegetation of central Brazil. In addition, we used an experimental approach exposing branches to 0 °C to measure temperature variation in internal branch tissue and test its relationship to bud protection and bark properties. We found that the majority of species (69%) showed medium to high bud protection against extreme temperatures; however, the degree of bud protection was not clearly related to bark properties, such as bark thickness and density. Bark density is a fundamental trait in determining protection against low temperatures (0 °C), since species with low bark density showed lower temperature variation in their internal branch tissues, independently of the bud protection degree. Bark properties and bud protection are two different (albeit related) strategies for the protection and persistence of savanna trees under extreme environmental temperatures and can explain ecological observations related to savanna tree responses after frost events.


Subject(s)
Cold Temperature , Grassland , Trees , Brazil , Plant Bark/anatomy & histology , Plant Bark/physiology
9.
Plant Physiol Biochem ; 147: 172-180, 2020 Feb.
Article in English | MEDLINE | ID: mdl-31865163

ABSTRACT

Plants that perform the Crassulacean acid metabolism (CAM), which obtain CO2 overnight and convert it mainly in malic acid, successfully grow in environments with water and nutrient shortages, that is partly associated with their higher water- and nitrogen-use efficiencies. Water and nutrient limitations can impair photosynthesis through the reduction of RuBisCO and increment of photorespiration, disturbing the plant carbon balance. In this context, we conducted a controlled experiment with the epiphytic C3-CAM bromeliad Guzmania monostachia to investigate how the combined water and nutritional deficits affect the activity of RuBisCO and its activation state (RAS), and to evaluate the efficiency of photosynthesis during the transition from C3 to CAM. Apart from an increase in CAM activity, bromeliads submitted to both water and nutritional deficits showed higher RAS values and unaltered RuBisCO activity compared to C3 bromeliads and, surprisingly, the maximum quantum efficiency of photosynthesis increased. Glucose, fructose and starch levels were maintained, while sucrose concentrations increased over time. These results, combined with the high RAS values, suggest an increased efficiency of RuBisCO functioning. Our results reinforce the ability of epiphytic bromeliads to deal with stressful habitats by a higher efficiency of RuBisCO during the transition to CAM, another feature that may allow their evolution in the epiphytic environment.


Subject(s)
Bromeliaceae , Photosynthesis , Ribulose-Bisphosphate Carboxylase , Bromeliaceae/enzymology , Photosynthesis/physiology , Ribulose-Bisphosphate Carboxylase/metabolism , Water/metabolism
10.
G3 (Bethesda) ; 8(11): 3577-3582, 2018 11 06.
Article in English | MEDLINE | ID: mdl-30185426

ABSTRACT

Estimates of different ancestral proportions in admixed populations are very important in population genetics studies, especially for the detection of population substructure effects in studies of case-control associations. Brazil is one of the most heterogeneous countries in the world, both from a socio-cultural and a genetic point of view. In this work, we investigated a previously developed set of 61 ancestry informative markers (AIM), aiming to estimate the proportions of four different ancestral groups (African, European, Native American and Asian) in Brazilian populations. To the best of our knowledge, this is the first study to use a set of AIM to investigate the genetic contribution of all four main parental populations to the Brazilian population, including Asian contribution. All selected markers were genotyped through multiplex PCR and capillary electrophoresis. The set was able to successfully differentiate the four ancestral populations (represented by 939 individuals) and identify their genetic contributions to the Brazilian population. In addition, it was used to estimate individual interethnic admixture of 1050 individuals from the Southeast region of Brazil and it showed that these individuals present a higher European ancestry contribution, followed by African, Asian and Native American ancestry contributions. Therefore, the 61 AIM set has proved to be a valuable tool to estimate individual and global ancestry proportions in populations mainly formed by these four groups. Our findings highlight the importance of using sets of AIM to evaluate population substructure in studies carried in admixed populations, in order to avoid misinterpretation of results.


Subject(s)
Racial Groups/genetics , Brazil , Electrophoresis, Capillary , Genetic Markers , Genotype , Humans , Polymerase Chain Reaction
12.
Toxicon ; 57(5): 764-71, 2011 Apr.
Article in English | MEDLINE | ID: mdl-21333665

ABSTRACT

The effects induced by Apis mellifera venom (AMV), melittin-free AMV, fraction with molecular mass < 10 kDa (F<10) or melittin in nociceptive and inflammatory pain models in mice were investigated. Subcutaneous administration of AMV (2, 4 or 6 mg/kg) or melittin-free AMV (1, 2 or 4 mg/kg) into the dorsum of mice inhibited both phases of formaldehyde-induced nociception. However, F<10 (2, 4 or 6 mg/kg) or melittin (2 or 3 mg/kg) inhibited only the second phase. AMV (4 or 6 mg/kg), but not F<10, melittin-free AMV or melittin, induced antinociception in the hot-plate model. Paw injection of AMV (0.05 or 0.10 mg), F<10 (0.05 or 0.1 mg) or melittin (0.025 or 0.050 mg) induced a nociceptive response. In spite of inducing nociception after paw injection, scorpion (Tityus serrulatus) or snake (Bothrops jararaca) venom injected into the dorsum of mice did not inhibit formaldehyde-induced nociception. In addition, AMV (6 mg/kg), but not F<10 (6 mg/kg) or melittin (3 mg/kg), inhibited formaldehyde paw oedema. Concluding, AMV, F<10 and melittin induce two contrasting effects: nociception and antinociception. AMV antinociception involves the action of different components and does not result from non-specific activation of endogenous antinociceptive mechanisms activated by exposure to noxious stimuli.


Subject(s)
Bee Venoms/toxicity , Inflammation/chemically induced , Melitten/toxicity , Pain/chemically induced , Analysis of Variance , Animals , Formaldehyde/toxicity , Male , Mice , Motor Activity/drug effects , Pain Measurement
13.
Toxicon ; 54(1): 23-32, 2009 Jul.
Article in English | MEDLINE | ID: mdl-19298834

ABSTRACT

Antimicrobial peptides are components of innate immunity that is the first-line defense against invading pathogens for a wide range of organisms. Here, we describe the isolation, biological characterization and amino acid sequencing of a novel neutral Glycine/Leucine-rich antimicrobial peptide from skin secretion of Leptodactylus pentadactylus named leptoglycin. The amino acid sequence of the peptide purified by RP-HPLC (C(18) column) was deduced by mass spectrometric de novo sequencing and confirmed by Edman degradation: GLLGGLLGPLLGGGGGGGGGLL. Leptoglycin was able to inhibit the growth of Gram-negative bacteria Pseudomonas aeruginosa, Escherichia coli and Citrobacter freundii with minimal inhibitory concentrations (MICs) of 8 microM, 50 microM, and 75 microM respectively, but it did not show antimicrobial activity against Gram-positive bacteria (Staphylococcus aureus, Micrococcus luteus and Enterococcus faecalis), yeasts (Candida albicans and Candida tropicalis) and dermatophytes fungi (Microsporum canis and Trichophyton rubrum). No hemolytic activity was observed at the 2-200 microM range concentration. The amino acid sequence of leptoglycin with high level of glycine (59.1%) and leucine (36.4%) containing an unusual central proline suggests the existence of a new class of Gly/Leu-rich antimicrobial peptides. Taken together, these results suggest that this natural antimicrobial peptide could be a tool to develop new antibiotics.


Subject(s)
Anti-Infective Agents/chemistry , Antimicrobial Cationic Peptides/chemistry , Ranidae/metabolism , Skin/chemistry , Amino Acid Sequence , Animals , Anti-Infective Agents/isolation & purification , Anti-Infective Agents/pharmacology , Antimicrobial Cationic Peptides/isolation & purification , Antimicrobial Cationic Peptides/pharmacology , Bacteria/drug effects , Female , Fungi/drug effects , Glycine/chemistry , Hemolysis/drug effects , Humans , Indicators and Reagents , Leucine/chemistry , Male , Mass Spectrometry , Microbial Sensitivity Tests , Molecular Sequence Data , Molecular Weight
14.
Aging Cell ; 7(6): 813-23, 2008 Dec.
Article in English | MEDLINE | ID: mdl-18778411

ABSTRACT

Large, long-lived species experience more lifetime cell divisions and hence a greater risk of spontaneous tumor formation than smaller, short-lived species. Large, long-lived species are thus expected to evolve more elaborate tumor suppressor systems. In previous work, we showed that telomerase activity coevolves with body mass, but not lifespan, in rodents: telomerase activity is repressed in the somatic tissues of large rodent species but remains active in small ones. Without telomerase activity, the telomeres of replicating cells become progressively shorter until, at some critical length, cells stop dividing. Our findings therefore suggested that repression of telomerase activity mitigates the increased risk of cancer in larger-bodied species but not necessarily longer-lived ones. These findings imply that other tumor suppressor mechanisms must mitigate increased cancer risk in long-lived species. Here, we examined the proliferation of fibroblasts from 15 rodent species with diverse body sizes and lifespans. We show that, consistent with repressed telomerase activity, fibroblasts from large rodents undergo replicative senescence accompanied by telomere shortening and overexpression of p16(Ink4a) and p21(Cip1/Waf1) cycline-dependent kinase inhibitors. Interestingly, small rodents with different lifespans show a striking difference: cells from small shorter-lived species display continuous rapid proliferation, whereas cells from small long-lived species display continuous slow proliferation. We hypothesize that cells of small long-lived rodents, lacking replicative senescence, have evolved alternative tumor-suppressor mechanisms that prevent inappropriate cell division in vivo and slow cell growth in vitro. Thus, large-bodied species and small but long-lived species have evolved distinct tumor suppressor mechanisms.


Subject(s)
Biological Evolution , Body Size/genetics , Genes, Tumor Suppressor/physiology , Longevity/genetics , Rodentia/genetics , Animals , Body Size/physiology , Cells, Cultured , Cellular Senescence/genetics , Cricetinae , Guinea Pigs , Longevity/physiology , Mice , Mice, Inbred C57BL , Rats , Rats, Inbred BN , Rats, Inbred F344 , Rodentia/physiology , Telomerase/physiology , Telomere/metabolism
15.
Biol Reprod ; 79(3): 578-84, 2008 Sep.
Article in English | MEDLINE | ID: mdl-18509159

ABSTRACT

In humans, adverse pregnancy outcomes (low birth weight, prematurity, and intrauterine growth retardation) are associated with exposure to urban air pollution. Experimental data have also shown that such exposure elicits adverse reproductive outcomes. We hypothesized that the effects of urban air pollution on pregnancy outcomes could be related to changes in functional morphology of the placenta. To test this, future dams were exposed during pregestational and gestational periods to filtered or nonfiltered air in exposure chambers. Placentas were collected from near-term pregnancies and prepared for microscopical examination. Fields of view on vertical uniform random tissue slices were analyzed using stereological methods. Volumes of placental compartments were estimated, and the labyrinth was analyzed further in terms of its maternal vascular spaces, fetal capillaries, trophoblast, and exchange surface areas. From these primary data, secondary quantities were derived: vessel calibers (expressed as diameters), trophoblast thickness (arithmetic mean), and total and mass-specific morphometric diffusive conductances for oxygen of the intervascular barrier. Two-way analysis of variance showed that both periods of exposure led to significantly smaller fetal weights. Pregestational exposure to nonfiltered air led to significant increases in fetal capillary surface area and in total and mass-specific conductances. However, the calibers of maternal blood spaces were reduced. Gestational exposure to nonfiltered air was associated with reduced volumes, calibers, and surface areas of maternal blood spaces and with greater fetal capillary surfaces and diffusive conductances. The findings indicate that urban air pollution affects placental functional morphology. Fetal weights are compromised despite attempts to improve diffusive transport across the placenta.


Subject(s)
Particulate Matter/toxicity , Placenta/anatomy & histology , Placenta/drug effects , Air Pollution/adverse effects , Animals , Animals, Newborn , Birth Weight/drug effects , Cities , Female , Litter Size/drug effects , Male , Mice , Models, Biological , Organ Size/drug effects , Placenta/blood supply , Placenta/ultrastructure , Pregnancy
16.
J Anat ; 210(4): 449-59, 2007 Apr.
Article in English | MEDLINE | ID: mdl-17362488

ABSTRACT

The effects of partial urethral obstruction on the detrusor muscle of rabbit urinary bladder were investigated using stereological sampling and estimation tools. Twelve female Norfolk rabbits (2.5-3.0 kg body weight) were divided into four groups: 3, 7 and 12 weeks after surgical intervention to produce a standard partial obstruction and unobstructed controls. Following removal, bladder axes (craniocaudal, dorsoventral and laterolateral) and organ weights were recorded. Bladders were prepared for light microscopy by multistage random sampling procedures. Stereological methods were used to estimate the volume of muscle and the packing density and total number of myocyte nuclei in each bladder. We also estimated mean myocyte volume and the mean cross-sectional area and length of myocytes. Group comparisons were made by one-way analysis of variance. Changes in bladder axes were mainly laterolateral and craniocaudal. Mean bladder weight increased roughly six-fold by 3 weeks and 17-fold by 12 weeks and was accompanied, on average, by 12- and 33-fold increases in total muscle volume. These variables did not differ at 3 and 7 weeks post-obstruction. Increases in muscle content were not accompanied by changes in packing densities but were associated with increases in the total numbers of myocyte nuclei (13-fold by 3 weeks, 28-fold by 12 weeks). Mean myocyte volume did not vary significantly between groups but cells in obstructed groups were shorter and wider. These findings support the notion that partial outflow obstruction leads to an increase in the number, but not mean volume, of myocytes. If due solely to myocyte mitosis, the total of 43 x 10(8) cells found at 12 weeks could be generated by the original complement of 15 x 10(7) cells if an average of only 2.1 x 10(6) new cells was produced every hour. In reality, even this modest proliferation rate is unlikely to be achieved because myocyte proliferation rates are very low and it is possible that new myocytes can arise by differentiation of mesenchymal or other precursor cells.


Subject(s)
Myocytes, Smooth Muscle/pathology , Urethral Obstruction/pathology , Urinary Bladder/pathology , Animals , Cell Count , Cell Size , Female , Hyperplasia , Models, Animal , Rabbits
17.
Aging Cell ; 6(1): 45-52, 2007 Feb.
Article in English | MEDLINE | ID: mdl-17173545

ABSTRACT

In multicellular organisms, telomerase is required to maintain telomere length in the germline but is dispensable in the soma. Mice, for example, express telomerase in somatic and germline tissues, while humans express telomerase almost exclusively in the germline. As a result, when telomeres of human somatic cells reach a critical length the cells enter irreversible growth arrest called replicative senescence. Replicative senescence is believed to be an anticancer mechanism that limits cell proliferation. The difference between mice and humans led to the hypothesis that repression of telomerase in somatic cells has evolved as a tumor-suppressor adaptation in large, long-lived organisms. We tested whether regulation of telomerase activity coevolves with lifespan and body mass using comparative analysis of 15 rodent species with highly diverse lifespans and body masses. Here we show that telomerase activity does not coevolve with lifespan but instead coevolves with body mass: larger rodents repress telomerase activity in somatic cells. These results suggest that large body mass presents a greater risk of cancer than long lifespan, and large animals evolve repression of telomerase activity to mitigate that risk.


Subject(s)
Biological Evolution , Body Weight/physiology , Longevity/physiology , Rodentia/physiology , Telomerase/metabolism , Animals , Cellular Senescence/physiology , Female , Male , Mice , Organ Specificity , Phylogeny , Rats , Rats, Inbred F344 , Species Specificity , Telomere/chemistry
18.
Cell Tissue Res ; 326(3): 737-48, 2006 Dec.
Article in English | MEDLINE | ID: mdl-16826374

ABSTRACT

Capybara might be a useful model for studying changes in cerebral circulation as the natural atrophy of the internal carotid artery (ICA) occurs in this animal at maturation. In this study, confocal and electron microscopy combined with immunohistochemical techniques were applied in order to reveal the changes in morphology and innervation to the proximal part of ICA in young (6-month-old) and mature (12-month-old) capybaras. Some features of the basilar artery (BA) were also revealed. The ICA of young animals degenerated to a ligamentous cord in mature animals. Immunolabelling positive for pan-neuronal marker protein gene product 9.5 but negative for tyrosine hydroxylase was observed in the proximal part of ICA at both ages examined. Axon varicosities positive for synaptophysin were present in the adventitia of ICA of young animals but were absent in the ligamentous cord of mature animals. In the ICA of young animals, adventitial connective tissue invaded the media suggesting that the process of regression of this artery began within the first 6 months of life. An increase in size of the BA was found in mature animals indicating increased blood flow in the vertebro-basilar system, possibly making capybara susceptible to cerebrovascular pathology (e.g. stroke). Capybara may therefore provide a natural model for studying adaptive responses to ICA regression/occlusion.


Subject(s)
Aging/physiology , Carotid Artery, Internal/metabolism , Carotid Artery, Internal/pathology , Rodentia/anatomy & histology , Animals , Atrophy , Basilar Artery/anatomy & histology , Basilar Artery/metabolism , Biomarkers/metabolism , Carotid Artery, Internal/innervation , Carotid Artery, Internal/ultrastructure , Female , Fluorescent Antibody Technique, Indirect , Immunohistochemistry , Microscopy, Confocal , Models, Biological , Synaptophysin/metabolism , Synaptophysin/ultrastructure
19.
Rev. Ciênc. Méd. Biol. (Impr.) ; 4(2): 125-130, maio-ago. 2005. ilus
Article in Portuguese | LILACS, BBO - Dentistry | ID: lil-472250

ABSTRACT

Garrotilho é uma doença infecto-contagiosa do trato respiratório superior dos eqüídeos, freqüente e importante, que causa pirexia, descarga nasal e abscedação dos linfonodos adjacentes. Acomete basicamente equídeos jovens, e é causada pelo Streptococcus equi â-hemolítico. Ocasionalmente, o garrotilho pode deixar seqüelas como sinusites, empiema das bolsas guturais e formação de abcessos à distância, principalmente no mesentério. O objetivo deste estudo é avaliar o timpanismo e empiema de bolsa gutural, clínico e cirúrgico, conseqüente a garrrotilho, ocorrido num eqüino jovem.


Subject(s)
Humans , Male , Female , Communicable Diseases , Empyema , Streptococcal Infections , Respiratory Tract Infections , Streptococcus equi
20.
J Mol Histol ; 36(1-2): 25-34, 2005 Feb.
Article in English | MEDLINE | ID: mdl-15703996

ABSTRACT

Little is known about cerebral vasculature of capybara, which seems may serve as a natural model of studying changes in cerebral circulation due to internal carotid artery atrophy at animal sexual maturation. This is the first study of the light- and electron-immunocytochemical localisation of endothelin-1 (ET-1) and ETA and ETB endothelin receptors in the basilar artery of capybaras (6 to 12-month-old females and males) using an ExtrAvidin detection method. All animals examined showed similar patterns of immunoreactivity. Immunoreactivity for ET-1 was detected in the endothelium and adventitial fibroblasts, whilst immunoreactivity for ETA and ETB receptors was present in the endothelium, vascular smooth muscle, perivascular nerves and fibroblasts. In endothelial cells immunoreactivity to ET-1 was pronounced in the cytoplasm or on the granular endoplasmic reticulum. Similar patterns of immunolabelling were observed for ETA and ETB receptors, though cytoplasmic location of clusters of immunoprecipitate seems dominant. These results suggest that the endothelin system is present throughout the wall of the basilar artery of capybara.


Subject(s)
Basilar Artery/cytology , Endothelin-1/analysis , Endothelium, Vascular/chemistry , Receptor, Endothelin A/analysis , Receptor, Endothelin B/analysis , Rodentia/anatomy & histology , Animals , Endothelium, Vascular/ultrastructure , Female , Male
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