Extent Of Amelioration Research Articles

Effects of long-term antipsychotic medication on brain instability in first-episode schizophrenia patients: a resting-state fMRI study

Early initiation of antipsychotic treatment plays a crucial role in the management of first-episode schizophrenia (FES) patients, significantly improving their prognosis. However, limited attention has been given to the long-term effects of antipsychotic drug therapy on FES patients. In this research, we examined the changes in abnormal brain regions among FES patients undergoing long-term treatment using a dynamic perspective. A total of 98 participants were included in the data analysis, comprising 48 FES patients, 50 healthy controls, 22 patients completed a follow-up period of more than 6 months with qualified data. We processed resting-state fMRI data to calculate coefficient of variation of fractional amplitude of low-frequency fluctuations (CVfALFF), which reflects the brain regional activity stability. Data analysis was performed at baseline and after long-term treatment. We observed that compared with HCs, patients at baseline showed an elevated CVfALFF in the supramarginal gyrus (SMG), parahippocampal gyrus (PHG), caudate, orbital part of inferior frontal gyrus (IOG), insula, and inferior frontal gyrus (IFG). After long-term treatment, the instability in SMG, PHG, caudate, IOG, insula and inferior IFG have ameliorated. Additionally, there was a positive correlation between the decrease in dfALFF in the SMG and the reduction in the SANS total score following long-term treatment. In conclusion, FES patients exhibit unstable regional activity in widespread brain regions at baseline, which can be ameliorated with long-term treatment. Moreover, the extent of amelioration in SMG instability is associated with the amelioration of negative symptoms.

Ameliorative Potential of Selenium against Bisphenol A-Induced Hepatotoxicity in Rats

Background: environmental pollutants affect various tissues. Bisphenol A, a compound used in making epoxy resins and polycarbonate plastics, induces many hazardous effects. Aim of the work: this work was designed to test the ameliorative potential of selenium against hepatotoxicity caused by bisphenol A. Materials and Methods: male rats were divided into four groups. Group 1 served as control, group 2 given sodium selenite, group 3 was administered with suspension of bisphenol A that is dissolved in corn oil. Rats of group 4 were administered with selenium plus bisphenol A. Liver specimens and blood samples were inspected after 3 and 6 weeks of treatment. Results: there was no statistical difference between control and selenium -administered rats in all parameters. Rats treated with bisphenol A suffered significant depression in weight whereas selenium administration decreased the effect on rat's weight. Bisphenol A administration induced blood vessels congestion, inflammatory infiltration, bile duct proliferation, cytoplasmic vacuolization and macrosteatosis while selenium administration improved liver histopathological criteria either after 3 or 6 weeks. Bisphenol A treatment elevated nuclear PCNA and caspase-3 expression in the cytoplasm and liver function enzymes (serum AST and ALT) and bilirubin. Again, selenium ameliorated these changes. In conclusion, bisphenolA exerted deleterious impact on rats' hepatocytes and serum biochemical parameters in a time-dependent manner. Selenium supplementation provides an extent of amelioration against bisphenol A- induced hepatotocixity.

The Clinically Active PARP Inhibitor AG014699 Ameliorates Cardiotoxicity but Does Not Enhance the Efficacy of Doxorubicin, despite Improving Tumor Perfusion and Radiation Response in Mice

AG014699 was the first inhibitor of the DNA repair enzyme PARP-1 to enter clinical trial in cancer patients. In addition to enhancing the cytotoxic effect of DNA-damaging chemotherapies, we have previously shown that AG014699 is vasoactive, thereby having the potential to improve drug biodistribution. The effectiveness of the clinical agent doxorubicin is confounded both by poor tumor penetration and cardiotoxicity elicited via PARP hyperactivation. In this study, we analyzed the impact of AG014699 on doxorubicin tolerance and response in breast (MDA-MB-231) and colorectal (SW620, LoVo) tumor models in vitro and in vivo. As anticipated, AG014699 did not potentiate the response to doxorubicin in vitro. In vivo, AG014699 did not influence the pharmacokinetics of doxorubicin; however, it did ameliorate cardiotoxicity. Both toxicity and extent of amelioration were more pronounced in male than in female mice. AG014699 improved vessel perfusion in both MDA-MB-231 and SW620 tumors; however, this neither led to improved tumor-accumulation of doxorubicin nor enhanced therapeutic response. In contrast, when combined with radiotherapy, AG014699 significantly enhanced response both in vitro and in vivo. Real-time assessment of tumor vessel function and companion histologic studies indicate that doxorubicin causes a profound antivascular effect that counters the positive effect of AG014699 on perfusion. These data indicate that although AG014699 can enhance response to some chemotherapeutic drugs via improved delivery, this does not apply to doxorubicin. PARP inhibitors may still be of use to counter doxorubicin toxicity, and if the gender effect translates from rodents to humans, this would have greater effect in males.

Water‐Stable Aggregation in Relation to the Normalized Stability Index

In spite of the good quality of soils in Hungary, soil structure is deteriorated by intensive tillage. Because of general dissimilarities between field and laboratory circumstances and therefore lack of comparability, the former results are questionable. An optimized method initiated by Six, Elliott, and Paustian (2000) was adapted to investigate changes in soil structure and quality caused by different kinds of added organic matters. Our samples originated from the long‐term fertilization experiments in Keszthely, western Hungary. The experiments were set up in 1960. The texture of the investigated soil is sandy loam; the type of soil is Eutric Cambisol (soil type FAO) or Alfisol (soil type USDA). Tillage and its depth was fall plowing to 25 cm. Crop rotation was maize–maize–potato–winter wheat–winter wheat. Samples were taken from depths of 0–20 and 20–30 cm, from the fallow, which had the same treatment as the potato field. Changes in soil structure were quantified by wet sieving. Soil structural stability was characterized by comparing aggregate size distribution after the use of a lower and a higher disruptive force, which was simulated by two different pretreatments. Determinations were done in triplicates. Soil structure may be improved by adding readily decomposable organic matter. The extent of amelioration depends on the chemical buildup and decomposability of the crop residues. Three different kinds of organic matters were investigated: (1) maize stem (M), (2) wheat straw (W), and (3) maize stem and wheat straw (MW). By comparing the aggregate stabilizing effects of the differently decomposable organic matters to each other and predicting the lower decomposability but persisting effect of M, the expected MW > M > W order was proven. These are parallel with those results of Harris, Chesters, and Allen (1966) and John et al. (2005), who observed decreasing aggregate stability in the M > W order. We observed increased macroaggregate stability in both macroaggregate fractions (2000–7000 µm and 250–2000 µm) in all three case of organic‐matter addition, but these newly formed bindings were easily broken up because of the weaker bindings of the higher aggregate hierarchical orders. This is remarkable mainly in the upper layer because crop residues were mixed to the upper layer and therefore could not have affected the lower one. Furthermore, adding organic materials has decreased the mass of the 53–250 µm microaggregate fraction in all treatments and depth layers and in addition in both pretretments. This proves that adding organic matter enhances the transient and temporary binding agents between microaggretages grouped into macroaggregates but that these bindings are temporal.

Effect of crop residues on soil aggregate stability

Soil structure may be improved by adding readily decomposable organic matter. The extent of amelioration depends on the chemical build-up and decomposability of the crop residues. Three different kinds of organic matters were investigated: (1) maize stem, (2) wheat straw, and (3) maize stem& wheat straw. Comparing the aggregate stabilizing effects of the differently decomposable organic matters to each other, the expected maize stem & wheat straw (mw) > maize stem (m) > wheat straw (w) order was proved.

Amelioration of teratogenesis. I. Modification of hydroxyurea-induced teratogenesis by the antioxidant propyl gallate.

Hydroxyurea (HU) is a potent teratogen which caused 100% embryotoxic effects in New Zealand white rabbits when injected sc on gestational day 12. These included a high percentage of resorptions and severe craniofacial, trunk and limb deformities of all survivors. Co-treatment of pregnant animals with the phenolic antioxidant propyl gallate (PG) resulted in amelioration of the embryotoxicity. Various amounts of PG (362-906 mg/kg) and HU (600-750 mg/kg) were eigher injected simultaneously or mixed together for periods of time up to 45 min. The extent of amelioration was dependent upon the amount of PG, although the highest dose of PG caused maternal toxicity. Simultaneous injections of HU and PG were not as efficacious as mixture of the two chemicals prior to injection. The length of time which the HU and PG mixture was allowed to stand prior to injection had no effect on the extent of amelioration. The protective action of PG resulted in significant linear reductions in both resorptions and specific malformations with increasing doses of PG. Histologic analysis of HU and HU-PG embryos disclosed that HU produced rapid cell death in the mesenchymal compartment of the embryo, particularly in the limb-buds, beginning at 2 h after treatment. Cell debris increased in amount until 8 h and remained extensive at 16 h. In contrast, HU-PG delayed the onset for cell death until 8 h. Nevertheless, at 16 h, the amount of cell debris in the limb-buds was appreciable. Thin layer chromatography (TLC) of HU-PG solution revealed no breakdown products or intermediate compounds suggesting that HU and PG do not react chemically. The presence of HU within both HU and HU-PG treated embryos was confirmed by TLC of embryonic sonicants. In contrast, TLC of embryonic extracts revealed PG only in HU-PG embryos. Light microscopy of other embryos from those same litters demonstrated extensive cell debris in the HU embryos but not in HU-PG embryos. It is suggested that the delay in onset of HU cytotoxicity is caused by the antioxidant properties of PG acting within the embryos, and that this may account for the amelioration of HU teratogenesis by PG.