Miracle-dz/UniFAR-FTUs huggingface dataset:
In vitro/in vivo evaluation of an optimized fast dissolving oral film containing olanzapine co-amorphous dispersion with selected carboxylic acids

Abstract Improvement of water solubility, dissolution rate, oral bioavailability, and reduction of first pass metabolism of OL (OL), were the aims of this research. Co-amorphization of OL carboxylic acid dispersions at various molar ratios was carried out using rapid solvent evaporation. Characterization of the dispersions was performed using differential scanning calorimetry (DSC), Fourier transform infrared spectrometry (FTIR), X-ray diffractometry (XRD), and scanning electron microscopy (SEM). Dispersions with highest equilibrium solubility were formulated as fast dissolving oral films. Modeling and optimization of film formation were undertaken using artificial neural networks (ANNs). The results indicated co-amorphization of OL-ascorbic acid through H-bonding. The co-amorphous dispersions at 1:2 molar ratio showed more than 600-fold increase in solubility of OL. The model optimized fast dissolving film prepared from the dispersion was physically and chemically stable, demonstrated short disintegration time (8.5 s), fast dissolution (97% in 10 min) and optimum tensile strength (4.9 N/cm2). The results of in vivo data indicated high bioavailability (144 ng h/mL) and maximum plasma concentration (14.2 ng/mL) compared with the marketed references. Therefore, the optimized co-amorphous OL-ascorbic acid fast dissolving film could be a valuable solution for enhancing the physicochemical and pharmacokinetic properties of OL.
Murine leptin deficiency alters Kupffer cell production of cytokines that regulate the innate immune system.

BACKGROUND & AIMS ob/ob mice are used to study the mechanisms that regulate the progression from steatosis to nonalcoholic steatohepatitis. The livers of ob/ob mice are depleted of CD4-positive natural killer cells, components of the innate immune system that induce anti-inflammatory cytokines. Although this may explain the sensitivity of fatty livers to lipopolysaccharide, why such hepatic CD4-positive natural killer cell depletion occurs is uncertain. Because leptin regulates macrophages, our hypothesis is that leptin deficiency alters Kupffer cell production of cytokines that inhibit (e.g., interleukin [IL]-12) or enhance (e.g., IL-15) hepatic CD4-positive natural killer cell viability. METHODS Kupffer cell cytokine production and the hepatic content of CD4-positive natural killer cells were compared in ob/ob and lean mice. ob/ob mice were then treated with IL-15 or leptin to determine whether either factor improved their immunologic abnormalities. RESULTS Compared with control Kupffer cells, ob/ob Kupffer cells produced less IL-15 basally and more IL-12 after lipopolysaccharide stimulation. Treatment of ob/ob mice with IL-15 for 1 week normalizes their hepatic CD4-positive natural killer cell content. Leptin increases the hepatic expression of IL-15 in ob/ob mice and partially replenishes their hepatic CD4-positive natural killer cells. CONCLUSIONS Leptin deficiency increases hepatic IL-12 and reduces hepatic IL-15 expression. The abnormal production of these Kupffer cell factors promotes hepatic CD4-positive natural killer cell depletion in ob/ob livers.
Hope Herth Index (HHI): A Validation Study in Italian Patients with Solid and Hematological Malignancies on Active Cancer Treatment

Aims and background Although hope is a widely used term, the experience of hope in patients with chronic or even life-threatening diseases is often disregarded due to the scarcity of carefully designed and validated assessment tools. The aim of this study was to validate the Hope Herth Index (HHI) questionnaire in the Italian population of patients with solid or hematological malignancies during active cancer treatment. Methods After the translation procedures, the psychometric properties of the Italian version of HHI were evaluated in 266 patients with non-advanced cancer cared for in four different settings. Summative scores ranged from 12–48, with a higher score denoting greater hope. Confirmative factorial analysis was performed to assess dimensionality. The test-retest reliability was assessed by means of the Lin concordance coefficient (two weeks' interval, 80 patients). Concurrent validity was assessed through the following questionnaires: Hospital Anxiety and Depression Scale (HADS), Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being (FACIT-Sp), Edmonton Symptom Assessment Scale (ESAS), and System Belief Inventory (SBI-15R). Results A total of 266 patients were enrolled. Confirmative factor analysis did not confirm the original three-factor solution, whereas a one-factor solution did perform well. Cronbach's alpha was 0.84 and the test-retest reliability was 0.64 (95% CI 0.51; 0.76). Large convergence was found with spiritual well-being as measured by the FACIT-Sp (0.69) and with anxiety-depression as measured by the HADS (inverse correlation: –0.51). Physical symptoms and religiousness were only slightly correlated, as expected. Conclusions The Italian version of HHI is a valid and reliable assessment tool – useful to initiate conversation with someone who is troubled but finds it difficult to talk – in patients with either solid or hematological malignancies on active cancer treatment during the non-advanced stages of the disease.
Study of the Effect of Route of Administration of Mesenchymal Stem Cells on Cisplatin-Induced Acute Kidney Injury in Sprague Dawley Rats

Background and Objectives Mesenchymal stem cells (MSCs) have been shown to ameliorate cisplatin-induced acute kidney injury (AKI). The present study compares the efficacy of different routes of MSCs administration on kidney damage and regeneration after cisplatin-induced AKI. Methods A single intraperitoneal injection of cisplatin (5 mg/kg) was used to induce AKI in 160 rats. MSCs (5×106) were given by either intravenous, intra-arterial or kidney sub capsular injection one day after cisplatin injection. Suitable control groups were included. Rats were sacrificed at 4, 7, 11 and 30 days after cisplatin injection. Kidney function parameters, kidney tissue oxidative stress markers, and scoring for renal tissue injury, regeneration and chronicity were all determined. Results MSCs by any routes were able to ameliorate kidney function deterioration and renal tissue damage induced by cisplatin. The overall results of the three routes were equal. Differences between the different routes in one parameter were transient and inconsistent with other parameters. Conclusions Changing the route of MSCs injection does not have a major influence on the outcome. Future evaluation should focus on differences between the routes of administration considering the long term safety.
Influences of hydration on post‐exercise cardiovascular control in humans

Dehydration is known to decrease orthostatic tolerance and cause tachycardia, but little is known about the cardiovascular control mechanisms involved. To test the hypothesis that arterial baroreflex sensitivity increases during exercise‐induced dehydration, we assessed arterial baroreflex responsiveness in 13 healthy subjects (protocol 1) at baseline (PRE‐EX) and 1 h after (EX‐DEH) 90 min of exercise to cause dehydration, and after subsequent intravenous rehydration with saline (EX‐REH). Six of these subjects were studied a second time (protocol 2) with intravenous saline during exercise to prevent dehydration. We measured heart rate, central venous pressure and arterial pressure during all trials, and muscle sympathetic nerve activity (MSNA) during the post‐exercise trials. Baroreflex responses were assessed using sequential boluses of nitroprusside and phenylephrine (modified Oxford technique). After exercise in protocol 1 (EX‐DEH), resting blood pressure was decreased and resting heart rate was increased. Cardiac baroreflex gain, assessed as the responsiveness of heart rate or R‐R interval to changes in systolic pressure, was diminished in the EX‐DEH condition (9.17 ± 1.06 ms mmHg−1vs. PRE‐EX: 18.68 ± 2.22 ms mmHg−1, P < 0.05). Saline infusion after exercise did not alter the increase in HR post‐exercise or the decrease in baroreflex gain (EX‐REH: 10.20 ± 1.43 ms mmHg−1; P > 0.10 vs. EX‐DEH). Saline infusion during exercise (protocol 2) resulted in less of a post‐exercise decrease in blood pressure and a smaller change in cardiac baroreflex sensitivity. Saline infusion caused a decrease in MSNA in protocol 1. We conclude that exercise‐induced dehydration causes post‐exercise changes in the baroreflex control of blood pressure that may contribute to, rather than offset, orthostatic intolerance.
Fibroma and fibrothecoma of the ovary: MR imaging findings.

PURPOSE To describe the morphologic and signal intensity characteristics on magnetic resonance (MR) images of fibromas and fibrothecomas. MATERIALS AND METHODS MR images of 11 female patients with histologically proved fibromas or fibrothecomas were reviewed, and morphologic and signal intensity characteristics of the lesions were analyzed. MR imaging findings were correlated with histologic findings. RESULTS All fibromas and fibrothecomas showed homogeneous low signal intensity on T1-weighted images. On T2-weighted images, the two smallest lesions showed homogeneous low signal intensity, and eight of the other nine lesions showed predominantly low signal intensity. Edema was noted only in larger lesions, and cystic degeneration was noted only in three of the largest lesions. On T2-weighted images, the percentage of low signal intensity in the lesion was not found to be related to lesion size, and the percentage of low signal intensity in fibromas was not significantly different from that in fibrothecomas (P = .55). Many lesions showed heterogeneous signal intensity; the solid component was distributed peripherally, and the cystic component was located centrally or eccentrically. Free intraperitoneal fluid was noted in 10 of 11 lesions and was not significantly correlated with lesion size (r = .52 and P = .10). CONCLUSION Because of their predominantly low signal intensity on T2-weighted images, fibromas and fibrothecomas display a relatively specific appearance on MR images.
Oxidation pathways for ozonation of azo dyes in a semi‐batch reactor: A kinetic parameters approach

Abstract In this study ozone and the H2O2/O3 oxidation system are used to decolorize aqueous solutions of Orange II (Or‐II) and Acid Red 27 (AR‐27). Investigations are carried out in a semi‐batch bubble column reactor. A system of series‐parallel reactions is proposed to describe the mechanism of dye oxidation. The stoichiometric ratio for the first reaction is found to be 1 mol dye per mol O3, while the overall ozone demand for both reactions one and two is found to be 5 and 6 moles for Or‐II and AR‐27 respectively. Molecular and radical kinetics are compared: a radical scavenger, t‐butanol, can be added to ensure only the molecular reaction of ozone, or hydrogen peroxide can be supplied through a peristaltic pump, to initiate radical reactivity. Results reveal that colour removal is ensured by direct ozone attack. For both dyes, TOC removal efficiencies of 50 ‐ 60 % are obtained by the action of the hydroxyl free radical. However, this is not improved by addition of H2O2, thus demonstrating that organic species alone ensure HO° radical production during ozonation. Both the mass transfer and the ozone reactivity with the dyes are considered to evaluate the kinetic parameters for the molecular pathway.
Biology and bionomics of bloodsucking ceratopogonids.

In recent years there has been increasing attention paid to three genera [Culicoides, Leptoconops, Forcipomyia (Lasiohelea)] of ceratopogonids, whose females feed on warm-blooded vertebrates. This habit makes them pests of man and livestock. They are a nuisance to humans living on the coast and in poorly drained inland areas, but they are most important as vectors of virus diseases that are transmitted to domestic animals. Culicoides are proven vectors of bluetongue to sheep and cattle (93) and have been incriminated in the transmission of horse sickness to equines and ephemeral fever to cattle (26). The involvement of bloodsucking ceratopogonids in the transmission of human and animal diseases was reviewed in 1965 (60) and their bionomics and control in 1962 (59) and 1969 (61). The present review refers only to work covered in the latter two articles where necessary for the appreciation of more recent research. Current interest in ceratopogonids has been fostered by a biannual news letter, Ceratopogonid Information Exchange, edited by J. Boorman, Animal Virus Research Institute, Pirbright, Woking, Surrey, U.K.
The Relationship of Personality Dimensions in Adult Male Rhesus Macaques to Progression of Simian Immunodeficiency Virus Disease

Studies of nonhuman primate personality have suggested that physiological correlates of relevant behavioral dimensions exist. The present study examined personality using techniques similar to those employed in human personality research. Adult male rhesus monkeys were each rated on 25 adjectives while living in their natal groups. Approximately 1.5 years later, 18 animals were inoculated with the simian immunodeficiency virus (SIV) and exposed to socially stable or socially unstable conditions. Behavior, viral load (SIV RNA), plasma cortisol concentrations, and the IgG response to SIV and to rhesus cytomegalovirus were measured at regular intervals. Multiple regression analyses revealed that the four personality dimensions (Sociability, Confidence, Equability, Excitability) were correlated with various measures. Following inoculation with SIV, animals higher in Sociability showed a more rapid decline in plasma cortisol concentrations, elevations in the anti-RhCMV IgG response, and a decline in SIV RNA. The results indicate that personality factors in rhesus monkeys do have physiological correlates that have significance for disease processes and that in the context of a social manipulation, Sociability, reflecting the tendency to engage in affiliative interactions, is an important factor in explaining outcome measures at early time points.
UV wavelength-dependent DNA damage and human non-melanoma and melanoma skin cancer

Ultraviolet (UV) irradiation from the sun has been epidemiologically and mechanistically linked to skin cancer, a spectrum of diseases of rising incidence in many human populations. Both non-melanoma and melanoma skin cancers are associated with sunlight exposure. In this review, we discuss the UV wavelength-dependent formation of the major UV-induced DNA damage products, their repair and mutagenicity and their potential involvement in sunlight-associated skin cancers. We emphasize the major role played by the cyclobutane pyrimidine dimers (CPDs) in skin cancer mutations relative to that of (6–4) photoproducts and oxidative DNA damage. Collectively, the data implicate the CPD as the DNA lesion most strongly involved in human cancers induced by sunlight.
Activation of Protein Kinase Cascades by Osmotic Shock (*)

Osmotic shock induces a variety of biochemical and physiological responses in vertebrate cells. By analyzing extracts obtained from rat 3Y1 fibroblastic cells exposed to hyper-osmolar media, we have found that mitogen-activated protein kinases (MAPKs) and stress-activated protein kinases (SAPKs, also known as JNKs) are both activated in response to osmotic shock. MAPKK1 (MEK1) was also activated markedly. Furthermore, Raf-1 and MEKK were activated strikingly by the osmotic shock. Activation of Raf-1 and MEKK in response to osmotic shock was detected also in PC12 cells, in which MEKK activation by the osmotic shock was much stronger than that by epidermal growth factor. Activation of SAPKs in PC12 cells by the osmotic shock was also more marked than that by epidermal growth factor. The activated MEKK phosphorylated not only MAPKKs but also XMEK2, which is distantly related to MAPKK. Recombinant wild-type XMEK2, but not kinase-negative XMEK2, was able to phosphorylate and activate recombinant SAPKα in vitro. In addition, this activity of XMEK2 was activated by the activated MEKK. These results suggest that the MAPK cascade consisting of Raf-1, MAPKK, and MAPK and the SAPK cascade consisting of MEKK, XMEK2, and SAPK are both activated in response to osmotic shock. Finally, it was found that XMEK2 is a good substrate for SAPK.
Albumin Binding as a General Strategy for Improving the Pharmacokinetics of Proteins*

Plasma protein binding can be an effective means of improving the pharmacokinetic properties of otherwise short lived molecules. Using peptide phage display, we identified a series of peptides having the core sequence DICLPRWGCLW that specifically bind serum albumin from multiple species with high affinity. These peptides bind to albumin with 1:1 stoichiometry at a site distinct from known small molecule binding sites. Using surface plasmon resonance, the dissociation equilibrium constant of peptide SA21 (Ac-RLIEDICLPRWGCLWEDD-NH2) was determined to be 266 ± 8, 320 ± 22, and 467 ± 47 nm for rat, rabbit, and human albumin, respectively. SA21 has an unusually long half-life of 2.3 h when injected by intravenous bolus into rabbits. A related sequence, fused to the anti-tissue factor Fab of D3H44 (Presta, L., Sims, P., Meng, Y. G., Moran, P., Bullens, S., Bunting, S., Schoenfeld, J., Lowe, D., Lai, J., Rancatore, P., Iverson, M., Lim, A., Chisholm, V., Kelley, R. F., Riederer, M., and Kirchhofer, D. (2001) Thromb. Haemost. 85, 379–389), enabled the Fab to bind albumin with similar affinity to that of SA21 while retaining the ability of the Fab to bind tissue factor. This interaction with albumin resulted in reduced in vivoclearance of 25- and 58-fold in mice and rabbits, respectively, when compared with the wild-type D3H44 Fab. The half-life was extended 37-fold to 32.4 h in rabbits and 26-fold to 10.4 h in mice, achieving 25–43% of the albumin half-life in these animals. These half-lives exceed those of a Fab′2 and are comparable with those seen for polyethylene glycol-conjugated Fab molecules, immunoadhesins, and albumin fusions, suggesting a novel and generic method for improving the pharmacokinetic properties of rapidly cleared proteins.
Characteristics of spray flames and the effect of group combustion on the morphology of flame-made nanoparticles

Characteristics of burning and non-burning sprays generated by a coaxial air-assist nozzle, previously used for the synthesis of ceramic nanoparticles by flame spray pyrolysis (FSP), are studied using phase Doppler anemometry. Also, the effect of droplet interaction on the overall combustion behavior of the spray (group combustion) and, consequently, on the characteristics of flame-made ceramic particles is investigated. A physical model is proposed which correlates the formation of inhomogeneous mixtures of micron-sized hollow particles and solid nanoparticles to the combustion mode: the precursor droplets which entirely evaporate in the hot flame are responsible for the formation of nanoparticles. The vapor species react, forming intermediate and product molecules and clusters that quickly grow to nanosized ceramic particles. On the other hand, under certain conditions, a small number of the droplets, particularly with large initial sizes, escape from the spray boundaries and become extinguished, producing large hollow ceramic particles. It is also possible that some of the large droplets, which lie within the spray core, do not entirely evaporate. These surviving droplets then form large particles which are usually hollow but can collapse to solid particles at sufficiently high temperatures. Also, a criterion for the formation of homogeneous ceramic nanoparticles is presented.
Body composition and surgical treatment of obesity. Effects of weight loss on fluid distribution.

Obesity is associated with absolute and relative expansion of the extracellular water compartment (ECW). The effects of substantial and prolonged weight reduction on body water distribution are unknown, however. The authors studied total body water (TBW) by tritiated water dilution, ECW by 35SO4 dilution, exchangeable sodium (Na(e)) by 24Na, and total body potassium (TBK) by 40K whole-body counting in 25 severely obese women (body mass index [BMI] = 48 +/- 7 kg.m-2, mean +/- standard deviation) aged 36 +/- 8 years before and at intervals after gastric restrictive (GR; n = 12) and malabsorptive (MA; n = 13) operations for obesity. Results are compared with a control group of 26 healthy normal-weight women (BMI = 21 +/- 2). Before operation, the obese patients had absolute elevations of all water compartments compared with controls, with significantly higher ratios of Na(e) to TBK (1.17 +/- 0.13 versus 0.91 +/- 0.10; p less than 0.05) and ECW to intracellular water (ICW) (E/I = 0.82 +/- 0.17 versus 0.63 +/- 0.06; p less than 0.05). After weight loss of 52 +/- 20 kg in MA and 47 +/- 19 kg in GR patients (nonsignificant between groups) to a stable level 22 +/- 8 months after operation, there were statistically significant reductions in TBW, ICW, TBK, and Na(e) in both groups, but a significant reduction in ECW only after GR. Adjusting for preoperative weight, duration of follow-up, and rate of weight loss, E/I was greater after MA than GR (1.09 +/- 0.25 versus 0.82 +/- 0.14; p less than 0.05). The elevated preoperative E/I ratio did not normalize with weight loss after surgery, and the response was related to the type of operation. The finding remains to be explained although the increased E/I after MA may reflect mild protein-calorie malnutrition not detectable in the blood. The persistence of elevated E/I with significant weight loss after GR might imply an intrinsic or irreversible imbalance of fluid distribution in obese patients.
The Tubifex tubifex Assay for the Determination of Acute Toxicity

An express (3-minute) test for acute toxicity determination by using the oligochaete annelid, Tubifex tubifex, is described. The EC50(Tubifex tubifex) [EC50(Tt)] for movement inhibition was calculated by using a concentration–response dependence. The reproducibility of the test was checked over several years and by several workers. Its applicability is limited to compounds which are soluble in water. The calculated EC50(Tt) indices correlate with LC50 values determined by using the fish, Pimephales promelas (96hour assay), and with ICG50 values determined by using the ciliate, Tetrahymena pyriformis (48-hour assay) with high statistical significance (r = 0.822, n = 35, and r = 0.927, n = 80, respectively). The correlation between the EC50(Tt) indices and rat oral LD50 values (48-hour assay) was r = 0.519 (n = 67). The correlation within organic compounds was closer (r = 0.635, n = 60) than with the heterogeneous series of chemicals. A similar trend was noticed for the correlation with mouse oral LD50 values (r = 0.479, n = 56) with the heterogeneous series of chemicals, as compared that with the series without inorganic salts (r = 0.605, n = 42), and similarly with mouse intraperitoneal LD50 values, where r = 0.543 (n = 50) with the heterogeneous series of chemicals and r = 0.893 (n = 33) with the series of organic chemicals.