Impact of wildfire recurrence on soil properties and organic carbon fractions.

The recurrence and severity of wildfire is on the rise due to factors like global warming and human activities. Mediterranean regions are prone to significant wildfire events, which cause extensive damage to ecosystems and soil properties. This study focuses on the municipality of Allande in south-western Asturias (Spain), a region highly affected by recurrent wildfires. In this regard, we sought to examine how the recurrence of such fires influences soil organic carbon fractionation and other soil parameters, such as nitrogen fractionation, pH, and cation exchange capacity. The study involved six sampling plots with between varying fire recurrence levels, from 0 to 4 events between 2005 and 2022. The results revealed some significant effects of wildfires recurrence on soil texture, inorganic elemental composition and CEC, but not on pH and CE. In soil affected by recurrent fires, labile carbon fractions (cold-water extractable & hot-water extractable), and fulvic acid concentrations decreased by up to 36%, 5%, and 45%, respectively in comparison with undisturbed soil. In contrast, humic acid concentration remained stable or increased in soils damaged by fire. Additionally, nitrogen species in soil were observed to decrease significantly in high recurrence scenarios, especially nitrate. On the basis of our findings, we conclude that wildfires impact the distinct fractions of organic carbon and nitrogen in soils and that this effect is aggravated by increasing recurrence.

B-Cell Responses in Chronic Chagas Disease: Waning of Trypanosoma cruzi-Specific Antibody-Secreting Cells Following Successful Etiological Treatment.

BACKGROUND: A drawback in the treatment of chronic Chagas disease (American trypanosomiasis) is the long time required to achieve complete loss of serological reactivity, the standard for determining treatment efficacy. METHODS: Antibody-secreting cells and memory B cells specific for Trypanosoma cruzi and their degree of differentiation were evaluated in adult and pediatric study participants with chronic Chagas disease before and after etiological treatment. RESULTS: T. cruzi-specific antibody-secreting cells disappeared from the circulation in benznidazole or nifurtimox-treated participants with declining parasite-specific antibody levels after treatment, whereas B cells in most participants with unaltered antibody levels were low before treatment and did not change after treatment. The timing of the decay in parasite-specific antibody-secreting B cells was similar to that in parasite-specific antibodies, as measured by a Luminex-based assay, but preceded the decay in antibody levels detected by conventional serology. The phenotype of total B cells returned to a noninfection profile after successful treatment. CONCLUSIONS: T. cruzi-specific antibodies in the circulation of chronically T. cruzi-infected study participants likely derive from both antigen-driven plasmablasts, which disappear after successful treatment, and long-lived plasma cells, which persist and account for the low frequency and long course to complete seronegative conversion in successfully treated participants.

[Bibliographic review of the efficacy of platelet-rich plasma treatment in lumbar disc herniation]. / Revisión bibliográfica de la eficacia del tratamiento con plasma rico en plaquetas en hernia de disco lumbar.

Platelet-rich plasma (PRP) is an autologous blood product containing growth factors and proteins, widely employed in the clinical setting for tissue repair. Robust evidence in basic science literature has facilitated clinical research involving PRP for patients with disc disease and lumbar pain. Degenerative disc disease (DDD) has been identified as a significant contributor to lower back pain, with approximately 40% of patients under 30 and 90% of those over 50 experiencing lumbar pain showing MRI findings consistent with degenerative changes in intervertebral discs. Regenerative medicine within the disc has primarily been studied in patients with chronic, untreatable lumbar pain. Objective: to understand the available evidence regarding the efficacy of PRP in lumbar disc herniation. By understanding the scientific evidence supporting PRP as a lumbar disc herniation treatment, a research project can be developed, providing the theoretical foundation for implementing this therapy in the Mexican population. A search was conducted using PUBMED, ClinicalKey (Elsevier), Medscape, Science Direct, and Google Scholar databases. Conclusions: despite promising results in several studies on intradiscal PRP injection, small sample sizes and non-standardized graft preparation procedures have hindered these research efforts.

El plasma rico en plaquetas (PRP) es un producto sanguíneo autólogo que contiene factores de crecimiento y proteínas y se ha utilizado en todo el entorno clínico para la reparación de tejidos. La fuerte evidencia en la literatura de ciencias básicas ha permitido la investigación clínica que involucra PRP para pacientes con enfermedad del disco y dolor lumbar. La enfermedad degenerativa del disco (DDD) se ha establecido como un importante contribuyente a la causa del dolor lumbar: aproximadamente el 40% de los pacientes menores de 30 años y el 90% de los pacientes mayores de 50 años que tienen dolor lumbar también muestran hallazgos de imágenes de resonancia magnética (IRM) que son consistentes con cambios degenerativos dentro de los discos intervertebrales. La medicina regenerativa intradiscal se ha estudiado principalmente en pacientes con dolor lumbar crónico intratable. Objetivo: conocer la evidencia disponible sobre la eficacia del PRP en hernias de disco lumbar. Al conocer la evidencia científica disponible del PRP como tratamiento de hernia discal lumbar se podrá desarrollar un proyecto de investigación, lo cual sustentará las bases teóricas para realizar esta terapia en la población mexicana. Se realizó búsqueda en base de datos PUBMED, ClinicalKey (Elsevier), Medscape, Science Direct, Google Scholar. Conclusiones: aunque varias investigaciones han arrojado resultados prometedores con respecto a la inyección intradiscal de PRP los tamaños de muestra pequeños y los procedimientos de preparación de injertos no estandarizados obstaculizaron estos esfuerzos de investigación.

Reuse and recycle solutions in refineries by ozone-based advanced oxidation processes: A statistical approach.

Fresh water sources are under pressure globally by the increasing population and consequently increasing production, which increases the water demand day by day. Thus, decreasing the industrial fresh water demand and wastewater production became crucial both for the water availability in the future and for its impact to the environment. This study examined the ozone-based treatments as the possible solution to a refinery to treat the effluent already treated by the traditional techniques to reach the final requirements for reuse and recycle purposes. The screening tests performed by fractional factorial design revealed that the significant parameters for the treatment were ozone feed ratio, H2O2 amount and processing time while pH was found insignificant for this case. Based on the box-Behnken response surface methodology for effluent collected after biological treatment, the significant parameters were optimized as the ozone ratio of 0.9 g/h, H2O2 amount of 47 mg/L and 60 min duration. However, in case of increasing the H2O2 amount to 80 mg/L the duration can be minimized to 37.5 min decreasing the energy and reagent consumption costs by a 37%, reaching a final total organic carbon (TOC) under 4 mg/L, that is the target for reuse possibilities.

Sequential combined treatment with allopurinol and benznidazole in the chronic phase of Trypanosoma cruzi infection: a pilot study.

OBJECTIVES: Even though the use of combined drugs has been proved to be effective in other chronic infections, assessment of combined treatment of antiparasitic drugs in human Chagas' disease has not been performed. Herein, a pilot study was conducted to evaluate the tolerance and side effects of a sequential combined treatment of two antiparasitic drugs, allopurinol and benznidazole, in the chronic phase of Trypanosoma cruzi infection. PATIENTS AND METHODS: Changes in total and T. cruzi-specific T and B cells were monitored during a median follow-up of 36 months. Allopurinol was administered for 3 months (600 mg/day) followed by 30 days of benznidazole (5 mg/kg/day) in 11 T. cruzi-infected subjects. RESULTS: The combined sequential treatment of allopurinol and benznidazole was well tolerated. The levels of T. cruzi-specific antibodies significantly decreased after sequential combined treatment, as determined by conventional serology and by a multiplex assay using recombinant proteins. The frequency of T. cruzi-specific interferon-γ-producing T cells significantly increased after allopurinol treatment and decreased to background levels following benznidazole administration in a substantial proportion of subjects evaluated. The levels of total naive (CD45RA + CCR7 + CD62L+) CD4 + and CD8 + T cells were restored after allopurinol administration and maintained after completion of the combined drug protocol, along with a decrease in T cell activation in total peripheral CD4 + and CD8 + T cells. CONCLUSIONS: This pilot study shows that the combination of allopurinol and benznidazole induces significant modifications in T and B cell responses indicative of a reduction in parasite burden, and sustains the feasibility of administration of two antiparasitic drugs in the chronic phase of Chagas' disease.

Seronegative conversion after incomplete benznidazole treatment in chronic Chagas disease.

In 12-18% of adult patients, treatment with benznidazole for chronic Chagas disease has to be discontinued because of side-effects. We identified and analysed a cohort of 81 adult patients with three positive tests for Trypanosoma cruzi infection and serological monitoring following incomplete treatment with benznidazole for a median of 10 days. Twenty percent of these patients (16/81) met the criteria of cure, showing that the optimal schedule of benznidazole administration remains to be determined.

QSPR in oral bioavailability: specificity or integrality?

During the last decade the technological advances in drug discovery changed the absorption, distribution, metabolism, excretion and toxicity (ADMET) profiles of New Chemical Entities (NCEs). Among ADMET processes, absorption plays an important role in the research and development of more effective orally administered drugs. Although significant progress has been made in in vitro, in situ and in vivo experimental determinations of absorption, the development of in silico methodologies has emerged as a cheaper and fast alternative to predict them. Even though several in silico models have been described in the literature to predict oral bioavailability and related properties, the prediction accuracy and their potential use is still limited. The low precision and high variability of data, the lack of a complete experimental and theoretical validation of in silico approach, and above all, the multi-factorial nature of the oral absorption term, make the development of predictive in silico models a thorny task. The present review discusses several important advances regarding the QSPR approaches used in the development of predictive oral bioavailability models. The importance of fixing the problem associated with data resource, as well as improving the reliability of in silico results is highlighted. Optimization of individual properties along the absorption process must be integrated in a multi-objective scenario for studying oral bioavailability behavior in the early drug discovery and development.

Cancer survival in Cuba, 1994-1995.

The population-based cancer registry in Cuba is a national cancer registry established in 1964; cancer registration is entirely done by passive methods. Data on survival from 13 cancer sites or types registered during 1994-1995 are reported. Follow-up has been carried out predominantly by passive methods, with median follow-up ranging from 13-54 months. The proportion with histologically verified diagnosis for various cancers ranged between 34-100%; death certificates only (DCOs) comprised 8-50%; 50-89% of total registered cases were included for the survival analysis. The 5-year age-standardized relative survival for selected cancers were breast (69%), colon (41%), cervix (56%), urinary bladder (64%), rectum (48%) and non-Hodgkin lymphoma (49%). The 5-year relative survival by age group showed no distinct pattern or trend, and was fluctuating. A decreasing survival with increasing clinical extent of disease was noted for all cancers studied. The data on survival trend revealed that the 5-year relative survival of most cancers diagnosed in 1994-1995 was greater than that in 1988-1989.

Endogenous and exogenous porphyrins as photosensitizers in the Hep-2 human carcinoma cell line.

The photodynamic activity of three photosensitizers (PS): AL-induced PPIX, the porphyrin derivative 5-(4-trimethylammoniumphenyl)-10, 5, 20-tris (2,4,6- trimethoxyphenyl) porphyrin (CP) and the molecular dyad porphyrin-C(60) (P-C(60)), the last two incorporated into liposomal vesicles, was evaluated on Hep-2 human larynx carcinoma cell line. ALA-induced accumulation of the endogenous PS PPIX, reached saturation values between 5 and 24 h incubation time; the maximal PPIX content was 5.7 nmol/106 cells. The same intracellular level was accumulated when the cationic porphyrin CP was used, while the amount of P-C(60) attained was 1.5 nmol/106 cells. Under violet-blue exciting light, the fluorescence of PPIX and P-C(60) was found in the cytoplasm showing a granular appearance indicating lysosomal localization. CP was mainly detected as a filamentous pattern characteristic of mitochondrial localization. No dark cytotoxicity was observed using 1mM ALA, 5 microM CP and 1 microM P-C(60) after 24 h incubation. Cell morphology was analyzed using Hoechst-33258, toluidine blue staining, TUNEL assay and DNA fragmentation, 24 h after irradiation with 54 J/cm2. When photosensitized with ALA and P-C(60), chromatine condensation characteristic of apoptotic cell death was found; instead, 58 % of necrotic cells were observed with CP. The results show that in the Hep-2 cells, of the three PS analyzed, the molecular dyad P-C(60) was more efficient than CP and PPIX, and confirm that PDT can induce different mechanisms of cell death depending on the PS and the irradiation dose.

Increased gap junctional intercellular communication is directly related to the anti-tumor effect of all-trans-retinoic acid plus tamoxifen in a human mammary cancer cell line.

Additive effects against tumor cells might be achieved by combining anti-neoplastic agents directed against one or more altered mechanisms in cancer. We investigated the participation of gap junctional intercellular communication (GJIC), which is commonly dysfunctional in tumor cells as a possible mediating mechanism of the effect of all-trans-retinoic acid (RA) and tamoxifen (Tx) in MCF-7 human breast cancer cell lines. The combination of RA + Tx stimulated GJIC in approximately 53 +/- 3% of MCF-7 cells as early as after 6 h of treatment remaining communicated through 144 h of culture. The GJIC enhancement occurred along with immunolocalization of Cx26 and 43 at the membrane of contacting cells and correlated with higher protein levels. Cx40 immunoreactive plaques were detected at cell-to-cell contacts during 48 h of RA + Tx treatment that did not involve higher protein expression, to the contrary, a downregulation occurred after 72 h of treatment. Cell proliferation inhibition upon RA + Tx exposure was observed with optimal effects at 96-120 h of culture with an accumulation of cells primarily in G2/M and G0/G1 cell cycle boundaries. An enhancement of the pre-existing E-cadherin levels was observed after drug exposure along with a downregulation of Bcl-2 and C-myc protein levels and a reduction of telomerase activity, suggesting partial tumor phenotype reversion. Blockage of the RA + Tx-induced GJIC with 18-beta-glycyrrhetinic acid (beta-Gly) prevented in 34% the inhibition of MCF-7 proliferation and the E-cadherin increment in 30% at 96 h of culture. GJIC blockage did not alter the downregulation of Bcl-2, c-Myc, or telomerase activity induced by RA + Tx. Our results showed the participation of GJIC as a mediator mechanism of the combined action of RA and Tx in MCF-7 cells. The chemopreventive modulation of GJIC might represent an approachable alternative for the improvement of cancer therapy.

Physiological parameters and biodistribution of 5,10,15,20-tetra (4-methoxyphenyl) porphyrin in rats.

Physiological parameters on hepatic and renal functionality and biodistribution, accumulation and elimination, in different organs of the 5,10,15,20-tetra (4-methoxyphenyl) porphyrin (TMP) were determined in Wistar rats. The transport of TMP by low-density (LDL) and high-density lipoproteins (HDL) was also investigated. The photosensitizer is accumulated in the spleen, where its concentration is significantly increased 21 d post-injection; it also accumulates in the liver and in a lower proportion, in the duodenum, and poorly in brain and muscle. The urine and serum biochemical parameters reached normal values both in control and treated groups. The glomerular filtrate rate was not affected by the TMP treatment in any of the studied times. These results would indicate that the sensitizer does not modify the renal glomerular function. TMP is mainly eliminated from the organism via the bile-gut pathway. Considering the total amount of porphyrin bound to both lipoproteins (LDL and HDL) in comparison with the total value of the TMP in serum, it can be inferred that a large amount of the agent is transported by lipoproteins in the plasma. This study proves information about the behavior of TMP in vivo under dark conditions. The results can be used to design photodynamic treatments using this porphyrin model as the sensitizer.

Synthesis and biological evaluation of methoxyphenyl porphyrin derivatives as potential photodynamic agents.

A new meso-2,4,6-trimethoxyphenyl porphyrin covalently linked to a 2',6'-dinitro-4'-trifluoromethylphenyl group by an amine bond 5 and its metal complex with Cd(II) 6 was prepared. The photodynamic activities of 5 and 6 were evaluated in vitro on Hep-2 cells. A considerable increase in the photocytotoxic effect was found for 6, which has higher singlet molecular oxygen, O(2)((1)Delta(g)), production.

Photodynamic studies of metallo 5,10,15,20-tetrakis(4-methoxyphenyl) porphyrin: photochemical characterization and biological consequences in a human carcinoma cell line.

The photodynamic activities of the free-base 5,10,15,20-tetrakis(4-methoxyphenyl)porphyrin (TMP) and their metal complexes with zinc(II) (ZnTMP), copper(II) (CuTMP) and cadmium(II) (CdTMP) have been compared in two systems: reverse micelle of n-heptane/sodium bis(2-ethylhexyl)sulfosuccinate/water bearing photooxidizable substrates and Hep-2 human larynx carcinoma cell line. The quantum yields of singlet molecular oxygen, O2(1 delta g), production (phi delta) of TMP, ZnTMP and CdTMP in tetrahydrofuran, were determined yielding values of 0.65, 0.73 and 0.73, respectively, while O2(1 delta g) formation was not detected for CuTMP. In the reverse micellar system, the amino acid L-tryptophan (Trp) was used as biological substrate to analyze the O2(1 delta g)-mediated photooxidation. The observed rate constants for Trp photooxidation (kobsTrp) were proportional to the sensitizer quantum yield of O2(1 delta g). A value of approximately 2 x 10(7) s-1 M-1 was found for the second-order rate constant of Trp (krTry) in this system. The response of Hep-2 cells to cytotoxicity photoinduced by these agents in a biological medium was studied. The Hep-2 cultures were treated with 1 microM of porphyrin for 24 h at 37 degrees C and the cells exposed to visible light. The cell survival at different light exposure levels was dependent on phi delta. Under these conditions, the cytotoxic effect increases in the order: Cu-TMP << TMP < ZnTMP approximately CdTMP, correlating with the production of O2(1 delta g). A similar behavior was observed in both the chemical and biological media indicating that the O2(1 delta g) mediation appears to be mainly responsible for the cell inactivation.

Photodynamic activity of 5,10,15,20-tetrakis(4-methoxyphenyl)porphyrin on the Hep-2 human carcinoma cell line: effect of light dose and wavelength range.

The photodynamic activity of 5,10,15,20-tetrakis(4-methoxyphenyl)porphyrin (TMP) has been investigated in two systems: reverse micelles of n-heptane/sodium bis(2-ethylhexyl)sulfosuccinate (AOT)/water-bearing photooxidizable substrates and on a Hep-2 human carcinoma cell line. The effect of variation in the light dose and wavelength range (360-800, 455-800, and 590-800 nm) was compared in both media. The aerobic singlet oxygen-mediated photooxidation of L-tryptophan (Trp) was used as a model of biological substrate in a micellar system. A considerable increase of the observed rate constants of Trp (k(Trp)(obs)) was noted, increasing the irradiated area of the TMP spectrum. In vitro, the survival curves of Hep-2 cells, treated with TMP, were markedly dependent on the light wavelength ranges used for irradiation. A linear behavior between k(Trp)(obs) and the photoinactivation rate of Hep-2 cells was found, indicating that the singlet oxygen (1O2 ) is the main species responsible for cell inactivation. These results contributed to an understanding of the photodynamic process yielded by this porphyrin in vitro and the sensitivity of Hep-2 cells to photodamage.

Effects of alpha-difluoromethylornithine on the Fas expression and apoptosis in Hep-2 cells

DFMO is an irreversible inhibitor of ornithine decarboxilase (ODC), the key enzyme in mammalian polyamine biosynthesis, and has been shown to induce apoptosis. In this paper, the relation between the effects of DFMO on the polyamine content, apoptotic index and Fas expression in HEP-2 cells was determined. Fas is a type I membrane protein with a molecular mass of 45 kDa, which mediates apoptosis. The results suggest that the treatment with the polyamine inhibitor DFMO induced the expression of the surface antigen Fas, which could be responsible for trigger apoptosis in these cells.

Effects of alpha-difluoromethylornithine on the Fas expression and apoptosis in Hep-2 cells

DFMO is an irreversible inhibitor of ornithine decarboxilase (ODC), the key enzyme in mammalian polyamine biosynthesis, and has been shown to induce apoptosis. In this paper, the relation between the effects of DFMO on the polyamine content, apoptotic index and Fas expression in HEP-2 cells was determined. Fas is a type I membrane protein with a molecular mass of 45 kDa, which mediates apoptosis. The results suggest that the treatment with the polyamine inhibitor DFMO induced the expression of the surface antigen Fas, which could be responsible for trigger apoptosis in these cells.(AU)

Expression of Fas antigen and apoptosis caused by 5,10,15, 20-tetra(4-methoxyphenyl)porphyrin (TMP) on carcinoma cells: implication for photodynamic therapy.

The photodynamic effects of 5,10,15, 20-tetra(4-methoxyphenyl)porphyrin (TMP) on a Hep-2 cell line were investigated. TMP toxicity in the dark and in relation to illumination with visible light was examined. Hep-2 cells were treated with different TMP concentrations (1, 5 and 10 microM). The uptake of TMP by Hep-2 cells increased with TMP concentration and an increase of the initial uptake rate was observed with increasing TMP concentrations. However, after 24 h of incubation, a similar value of intracellular TMP concentration was reached at all three concentrations of TMP added. Cell toxicity induced by TMP was analyzed in the dark at different concentrations of the photosensitizer and at several incubation periods. The cell mortality obtained after exposure of the cell cultures to visible light was exclusively due to the photosensitization effect of TMP produced by light irradiation. Staining with the hematoxylin-eosin method demonstrated that treatment with TMP, followed by exposure to visible light, notably increased the apoptotic figures. Fas antigen was only expressed in these conditions. The results contribute to the understanding of the photodynamic therapy (PDT) mechanism produced by TMP on Hep-2 carcinoma cell line.

Molecular basis of cancer and clinical applications.

This article attempts to show the vertiginous advances that exist today in the concept of what cancer is. The authors chose some multiple biologic concepts that have enabled the progress in the knowledge of this disease to occur at a speed no one could imagine until recently. Although the areas and biologic problems that remain to be solved are more numerous and complex than they expected, the basic fundamentals already partially understood and the multidisciplinary integration of the various medical specialties with biomolecular research enable physicians to face the next millennium with great optimism about the possibilities of therapeutic success, prevention, and effective early diagnosis.

Effects of alpha-difluoromethylornithine on the Fas expression and apoptosis in Hep-2 cells.

DFMO is an irreversible inhibitor of ornithine decarboxilase (ODC), the key enzyme in mammalian polyamine biosynthesis, and has been shown to induce apoptosis. In this paper, the relation between the effects of DFMO on the polyamine content, apoptotic index and Fas expression in HEP-2 cells was determined. Fas is a type I membrane protein with a molecular mass of 45 kDa, which mediates apoptosis. The results suggest that the treatment with the polyamine inhibitor DFMO induced the expression of the surface antigen Fas, which could be responsible for trigger apoptosis in these cells.