Epidemiology of Tropical Neglected Diseases in Ecuador in the Last 20 Years

Background

Tropical and zoonotic diseases are major problems in developing countries like Ecuador. Poorly designed houses, the high proportion of isolated indigenous population and under developed infrastructure represent a fertile environment for vectors to proliferate. Control campaigns in Ecuador over the years have had varying success, depending on the disease and vectors targeted.

Aims

In our study we analyse the current situation of some neglected diseases in Ecuador and the efficiency of the control campaigns (by measuring changes in numbers of cases reported) that the Ecuadorian government has been running to limit the spread of these infectious and parasitic diseases.

Results

Our study reveals that Brucellosis, Chagas Disease, Rabies and Onchocerciasis have been controlled, but small outbreaks are still detected in endemic areas. Leptospirosis and Echinococcosis have been increasing steadily in recent years in Ecuador since the first records. The same increase has been reported world-wide also. Better diagnosis has resulted in a higher number of cases being identified, particularly with regard to the linking of outdoor activities and contact with farm animals as contributing vectors. Improvements in diagnosis are due to regular professional training, implementation of automatized systems, establishing diagnosis protocols and the creation of an epidemiological vigilance network that acts as soon as a case is reported.

Conclusion

Control campaigns performed in Ecuador have been successful in recent years, although natural phenomena limit their efficiency. Leptospirosis and Echinococcosis infections remain a growing problem in Ecuador as it is worldwide.     

The interaction between thymine DNA glycosylase and nuclear receptor coactivator 3 is required for the transcriptional activation of nuclear hormone receptors

The cellular counterpart of the “soluble” guanylyl cyclase found in tissue homogenates over 30 years ago is now recognized as the physiological receptor for nitric oxide (NO). The ligand-binding site is a prosthetic haem group that, when occupied by NO, induces a conformational change in the protein that propagates to the catalytic site, triggering conversion of GTP into cGMP. This review focuses on recent research that takes this basic information forward to the beginnings of a quantitative depiction of NO signal transduction, analogous to that achieved for other major transmitters. At its foundation is an explicit enzyme-linked receptor mechanism for NO-activated guanylyl cyclase that replicates all its main properties. In cells, NO signal transduction is subject to additional, activity-dependent modifications, notably through receptor desensitization and changes in the activity of cGMP-hydrolyzing phosphodiesterases. The measurement of these parameters under varying conditions in rat platelets has made it possible to formulate a cellular model of NO-cGMP signaling. The model helps explain cellular responses to NO and their modification by therapeutic agents acting on the guanylyl cyclase or phosphodiesterase limbs of the pathway.     

Oxidative stress during aging of the yeast in a stationary culture and its attenuation by antioxidants

Oxidative stress during aging of Saccharomyces cerevisiae in stationary culture was documented by demonstration of progressive increase in the formation of superoxide, decrease in the content of acid‐soluble thiols and of acid‐soluble antioxidant capacity of cell extracts, and accumulation of aldehydes and protein carbonyl groups in two yeast strains and decreases in activities of antioxidant enzymes. Cells of a CuZn‐SOD (superoxide dismutase)‐1‐deficient strain showed a higher loss of viability than cells of an isogenic wild‐type strain. Cell survival was augmented, and changes in biochemical parameters were ameliorated, by addition of exogenous antioxidants (ascorbic acid, glutathione and melatonin) in both strains.     

Design of riboflavin-presenting PAMAM dendrimers as a new nanoplatform for cancer-targeted delivery

This communication describes the synthesis and in vitro biological evaluation of novel generation 5 PAMAM dendrimers conjugated with riboflavin as a targeting ligand. Cell-based experiments demonstrated that a dendrimer conjugated with riboflavin is able to undergo cellular binding and uptake in KB cells, and when the dendrimer is also conjugated with methotrexate, the riboflavin dendrimer conjugate can potently inhibit cell growth.     

Plasma-mediated release of morphine from synthesized prodrugs

Two morphine prodrugs (‘PDA’ and ‘PDB’) were synthesized and the kinetics of esterase-mediated morphine release from these prodrugs were determined when incubated with plasma from different animal species. Morphine was rapidly released from PDA by all species plasma with the maximum reached within 5–10 min; the released morphine was biologically active as determined by an in vitro cAMP assay. The morphine was released from PDB at a slower and species-dependent rate (mouse > rat > guinea pig > human). Morphine’s release from PDB appeared to be mediated by carboxyl esterases as the release was inhibited by the carboxyl esterase inhibitor benzil. PDA nor PDB induce cytotoxicity in the neuronal cell lines SK-NSH and SH-SY5Y. The carboxyl and amino functional moieties present on the linker portions of PDA and PDB, respectively, may facilitate their conjugation to nanoparticles to tailor morphine pharmacokinetics and specific targeting. These studies suggest the potential clinical utility of these prodrugs for morphine release at desired rates by administration of their mixture at selected ratios.     

Frequency of Hospitalization for Angina Pectoris,Stroke, and Peripheral Venous Thrombosis and Its Relationship to Elements in Rainwater in Opole Voivodship,Poland, During 2000–2002

The content of elements in rainwater is an indirect indicator of its occurrence in air dust. This is sometimes referred to as rain fallout and is investigated in applied environmental pollution monitoring schemes. The annual content of elements in rainwater may be recognized as good index for assessing influence of those environmental factors on human body. The possible relationship between the concentrations of selected elements in rainwater and the frequency of hospitalization by reason of angina pectoris, stroke, and peripheral venous thrombosis was investigated in the Opole Voivodship (Poland) area during the period 2000–2002. There is a relatively high or partly significant correlation between frequency of hospitalization by reason of these conditions and content of lead, cadmium, chromium, zinc, and chloride in rainwater. Significant gender-dependent differences were observed only in peripheral venous thrombosis, where important correlations with lead, cadmium, and chromium were found only in men.     

Non-malignant thyroid diseases after a wide range of radiation exposures

The thyroid gland is one of the most radiosensitive human organs. While it is well known that radiation exposure increases the risk of thyroid cancer, less is known about its effects in relation to non-malignant thyroid diseases. The aim of this review is to evaluate the effects of high- and low-dose radiation on benign structural and functional diseases of the thyroid. We examined the results of major studies from cancer patients treated with high-dose radiotherapy or thyrotoxicosis patients treated with high doses of iodine-131, patients treated with moderate- to high-dose radiotherapy for benign diseases, persons exposed to low doses from environmental radiation, and survivors of the atomic bombings who were exposed to a range of doses. We evaluated radiation effects on structural (tumors, nodules), functional (hyper- and hypothyroidism), and autoimmune thyroid diseases. After a wide range of doses of ionizing radiation, an increased risk of thyroid adenomas and nodules was observed in a variety of populations and settings. The dose response appeared to be linear at low to moderate doses, but in one study there was some suggestion of a reduction in risk above 5 Gy. The elevated risk for benign tumors continues for decades after exposure. Considerably less consistent findings are available regarding functional thyroid diseases including autoimmune diseases. In general, associations for these outcomes were fairly weak, and significant radiation effects were most often observed after high doses, particularly for hypothyroidism. A significant radiation dose-response relationship was demonstrated for benign nodules and follicular adenomas. The effects of radiation on functional thyroid diseases are less clear, partly due to the greater difficulties encountered in studying these diseases.     

The ratio of amount of haemoglobin to total surface area of erythrocytes in mammals

The literature provides all the data needed to calculate the ratio between the amount of haemoglobin and the total surface area of erythrocytes in 54 species of mammals ranging in body mass from 2.5 g to more than 1000 kg. Analysis shows that the concentration of haemoglobin (Hb; g%) does not depend on the body mass of the mammals studied. The number of erythrocytes in 1 mm³ of blood (RBC; 10⁶×mm⁻³) is significantly lower, and the diameter of these cells significantly higher, among larger mammals as opposed to smaller ones. The result is that the total surface area of erythrocytes in 1 mm³ of blood (TSAE; mm²×mm⁻³) is significantly lower among larger mammals, while the Hb/TSAE ratio (pg×μm⁻²) is significantly greater. These results point to the smaller size of erythrocytes of smaller mammals permitting much greater numbers to exist, thereby producing a greater TSAE and smaller Hb/TSAE ratio. The greater total surface area of red blood cells per unit volume of blood in small mammals can in turn be presumed to allow for full saturation of haemoglobin by oxygen, even where the period of contact between erythrocytes and air in the lungs is shorter than in their larger counterparts.

     

Mitochondria-mediated ATP depletion by anti-cancer agents of the jasmonate family

Jasmonates are plant stress hormones that induce suppression of proliferation and death in cancer cells, while being selectively inactive towards non-transformed cells. Jasmonates can overcome apoptotic blocks and exert cytotoxic effects on drug-resistant cells expressing p53 mutations. Jasmonates induce a rapid depletion of ATP in cancer cells. Indeed, this steep drop occurs when no signs of cell death are detectable yet. Experiments using modulators of ATP synthesis via glycolysis or oxidative phosphorylation suggest that the latter is the pathway suppressed by jasmonates. Consequently, the direct effects of jasmonates on mitochondria were evaluated. Jasmonates induced cytochrome c release and swelling in mitochondria isolated from cancer cells but not from normal ones. Thus, the selectivity of jasmonates against cancer cells is rooted at the mitochondrial level, and probably exploits differences between mitochondria from normal versus cancer cells. These findings position jasmonates as promising anti-cancer drugs acting via energetic depletion in neoplastic cells.