Alterations In Physical State Research Articles

Analysis of the Socio-Health Situation of People in Humanitarian Crisis ″Case of Repressed from Congo-Brazzaville″

Context: The returnees from Congo Brazaville were received by the town hall of Kinshasa which brought them to Maluku. From there, those with closer family members went home, but the others and their children settled around the Cardinal Malula stadium for lack of accommodation. Purpose: This study is carried out with the aim of analyzing the socio-sanitary situation of people expelled from Brazzaville based around the municipality of Kinshasa. Methods: A descriptive cross-sectional survey made it possible, by interview and direct observation with the support of an interview guide, to collect information from 321 Congolese from the DRC expelled from the Republic of Congo, living in the commune of Kinshasa. This information was statistically analyzed using SPSS version 21 software. Results: It emerges from the descriptive analysis that the majority of respondents, ie 68.2%, were housed in tents. 84.4% experienced both physical and moral violence. 62.6% had an altered physical state. The most frequent problems include: lack of access to health care (100%); insalubrity (80.9%); malaria associated with other pathologies (80.8%) or alone and lack of access to drinking water (74.7%). From the inferential analysis, it emerges that the factors associated with the state of health of the repressed were: poor bowel management resulting in the use of stage [RR = 3.4 (1.70-6.69); p ˂ 0.000] or open air [RR = 2.93 (1.38 – 6.23); p ˂ 0.005] instead of a latrine; violence [RR = 2.91 (2.07 – 4.08); caring for at least 5 children [RR = 1.71 (1.21–2.41); p ˂ 0.002] as well as divorce [RR = 1.49 (1.16 – 1.92); p ˂ 0.002]. Conclusion: The socio-sanitary situation of those expelled from Brazzaville was not favourable. The direct involvement of the political and health authorities of the DRC with the support of national or international organizations would allow the proper management of humanitarian crises in the country.

Preparation of indapamide-HP-β-CD and indapamide-PVP nanoparticles by supercritical antisolvent technology: Experimental and DPD simulations

The poor aqueous solubility of indapamide (INP) limits its applicability in various biomedical applications. To overcome this issue, nanosized INP particles (INP-HP-β-CD NPs and INP-PVP-K30 NPs) were fabricated using the supercritical antisolvent (SAS) approach to improve the bioavailability of INP. The process, formula, and supercritical antisolvent process were optimized using single-factor and orthogonal methods. The tiny INP-HP-β-CD NPs with a particle size of 142.5 nm and INP-PVP-K30 NPs with a particle size of 150.4 nm were obtained under optimum conditions. Further analysis and characterization, such as SEM, FTIR, XRD, DSC, 1H NMR, and dissipative particle dynamics (DPD) simulations, were carried out to verify the formation mechanism of the INP complex nanoparticles. The altered physical state of INP from crystalline to amorphous loaded onto the polymer resulted in a significant improvement in the solubility and dissolution rate and high biocompatibility with cells compared to raw INP. Therefore, we propose that INP nanoparticles processed by a supercritical antisolvent process can be used as an advanced drug delivery system, especially for insoluble drugs.

Phosphatidylserine decarboxylase governs plasma membrane fluidity and impacts drug susceptibilities of Candida albicans cells

Plasma membrane (PM) lipid composition imbalances affect drug susceptibilities of the human pathogen Candida albicans. The PM fundamental structure is made up of phospholipid bilayer where phosphatidylethanolamine (PE) contributes as second major phospholipid moieties, which is asymmetrically distributed between the two leaflets of the bilayer. PSD1 and PSD2 genes encode phosphatidylserine decarboxylase which converts phosphatidylserine (PS) into PE in C. albicans cells. Genetic manipulation of PSD1 and PSD2 genes is known to impact virulence, cell wall thickness and mitochondrial function in C. albicans. In the present study, we have examined the impact of PSD1 and PSD2 deletion on physiochemical properties of PM. Our fluorescence recovery after photobleaching (FRAP) experiments point that the PM of psd1Δ/Δ psd2Δ/Δ mutant strain displays increased membrane fluidity and reduced PM dipole potential. Further, the result of PSD1 and PSD2 deletion on the thermotropic phase behavior monitored by differential scanning calorimetry (DSC) showed that in comparison to WT, the apparent phase transition temperature is reduced by ~3 °C in the mutant strain. The functional consequence of altered physical state of PM of psd1Δ/Δ psd2Δ/Δ mutant strain was evident from observed high diffusion of fluorescent dye rhodamine 6G and radiolabelled fluconazole (FLC). The higher diffusion of FLC resulted in an increased drug accumulation in psd1Δ/Δ psd2Δ/Δ mutant cells, which was manifested in an increased susceptibility to azoles. To the best of our knowledge, these results constitute the first report on the effect of the levels of phospholipid biosynthesis enzyme on physiochemical properties of membranes and drug susceptibilities of Candida cells.

Continuous nanonization of lonidamine by modified-rapid expansion of supercritical solution process

Despite the significant advancements in the pharmaceutical manufacturing process, the aqueous solubility of most of the potent drugs has remained as an unresolved problem during the formulation development and drug delivery processes. To address this critical issue, we modified the continuous-rapid expansion of supercritical solution (RESS-C) process, which is incessant, stable and well-regulated. Initially, the solubility of lonidamine (LND) in supercritical carbon dioxide (SC-CO2) was tested using a static analytical method at altered critical conditions (T: 308.15-328.15K, P: 10.0-30.0MPa). Under optimized conditions (LND conc.- 0.5% (w/v), flow rate- 1.0mL/min, T- 328.15K, P- 20.0MPa and CO2 flow rate- 30.0g/min), the modified RESS-C process resulted in nano-sized spheres with a smooth surface and a narrow particle size distribution. Further, the crystal properties of the samples and their molecular interactions were elucidated. The altered physical state of RESS-C processed LND from crystalline to amorphous resulted in the solubility improvement and also enhanced the in vitro antiproliferative effects compared to the unprocessed LND, demonstrating the potential of the modified RESS-C process in improving the bioavailability of poorly water-soluble drugs.

Short-term variability of the Sun-Earth system: an overview of progress made during the CAWSES-II period

This paper presents an overview of results obtained during the CAWSES II period on the short term variability of the Sun and how it affects the near Earth space environment. CAWSES II was planned to examine the behavior of the solar terrestrial system as the solar activity climbed to its maximum phase in solar cycle 24. After a deep minimum following cycle 23, the Sun climbed to a very weak maximum in terms of the sunspot number in cycle 24 (MiniMax24), so many of the results presented here refer to this weak activity in comparison with cycle 23. The short term variability that has immediate consequence to Earth and geospace manifests as solar eruptions from closed field regions and high speed streams from coronal holes. Both electromagnetic (flares) and mass emissions (coronal mass ejections, CMEs) are involved in solar eruptions, while coronal holes result in high speed streams that collide with slow wind forming the so called corotating interaction regions (CIRs). Fast CMEs affect Earth via leading shocks accelerating energetic particles and creating large geomagnetic storms. CIRs and their trailing high speed streams (HSSs), on the other hand, are responsible for recurrent small geomagnetic storms and extended (days) of auroral zone activity, respectively. The latter lead to the acceleration of relativistic magnetospheric killer electrons. One of the major consequences of the weak solar activity is the altered physical state of the heliosphere that has serious implications for the shock-driving and storm causing properties of CMEs. Finally, a discussion is presented on extreme space weather events prompted by the 2012 July 23 super storm event that occurred on the backside of the Sun. Many of these studies were enabled by the simultaneous availability of remote-sensing and in situ observations from multiple vantage points with respect to the Sun Earth line.

Alterations in physical state of silver nanoparticles exposed to synthetic human stomach fluid

The bioavailability of ingested silver nanoparticles (AgNPs) depends in large part on initial particle size, shape and surface coating, properties which will influence aggregation, solubility and chemical composition during transit of the gastrointestinal tract. Citrate-stabilized AgNPs were exposed to synthetic human stomach fluid (SSF) (pH 1.5) and changes in size, shape, zeta potential, hydrodynamic diameter and chemical composition were determined during a 1h exposure period using Surface Plasmon Resonance (SPR), High Resolution Transmission Electron Microscopy/Energy Dispersive X-ray Spectroscopy (TEM/EDS), Dynamic Light Scattering (DLS) and X-ray Powder Diffraction (XRD) combined with Rietveld analysis. Exposure of AgNPs to SSF produced a rapid decrease in the SPR peak at 414nm and the appearance of a broad absorbance peak in the near infrared (NIR) spectral region. During exposure to SSF, changes in zeta potential, aggregation and morphology of the particles were also observed as well as production of silver chloride which appeared physically associated with particle aggregates.

Facile synthesis of 3D cubic mesoporous silica microspheres with a controllable pore size and their application for improved delivery of a water-insoluble drug

A facile and simplified method was developed for the synthesis of 3D cubic mesoporous SBA-16 with both a spherical morphology and controllable pore size. The addition of CTAB during the synthesis allowed not only good control over the macroscopic morphology but also a significant reduction in the synthesis time. Notably, the pore size can simultaneously be adjusted by simply controlling the heating temperature. The pharmaceutical performance of the resulting SBA-16 for the delivery of the water-insoluble drug indomethacin (IMC), a non-steroidal anti-inflammatory agent used as a model drug, was systematically studied using nitrogen adsorption, powder X-ray diffraction, differential scanning calorimetry, infrared spectrometry and in vitro dissolution investigations. It was found that IMC could be effectively loaded into mesoporous SBA-16 via the solvent deposition method. An altered physical state and a marked improvement in the dissolution rate were observed for IMC after being loaded into SBA-16 microspheres. In particular, SBA-16 microspheres with the largest pore size (9.0 nm) and highly open and accessible pore networks exhibited the fastest drug release profile. We envisage that the improved drug delivery profiles obtained using SBA-16 as described in our work will offer an interesting option for the formulation of poorly water-soluble drugs.

Alterations of erythrocyte structure and cellular susceptibility in patients with chronic renal failure: Effect of haemodialysis and oxidative stress

The aim of this study was to investigate erythrocytes rheological behaviour, membrane dynamics and erythrocytes susceptibility to disintegration upon strong oxidative stress induced by dialysis or by external H2O2 among patients with CRF. EPR spectrometry was used to investigate alterations in physical state of cellular components. Generated ROS production induced: (1) significant increase of membrane fluidity in CRF erythrocytes treated with H2O2 (p<0.005) and at 60 min of haemodialysis (p<0.05), (2) significant decrease of cytoskeletal protein–protein interactions (p<0.005) and (3) cellular osmotic fragility (p<0.0005). H2O2 exacerbated these changes. Erythrocytes from CRF patients have changed rheological behaviour and present higher susceptibility to disintegration. Erythrocytes membrane characteristics indicate that CRF patients possess younger and more flexible cells, which are more susceptible to oxidative stress. This may contribute to the shortened survival of young erythrocytes in CRF patients.

Qu'est-ce qu'une maladie ?

The concept of disease is more complex than it may seem. Disease is both a natural category and a social construction. Medical anthropology distinguishes between three realities under the different words defining "disease": the biological abnormalities (disease), the subjective experience of altered physical state (illness), and the process of socialization of pathological episodes (sickness). The constructivist perspective of the sociology of science shows that scientific knowledge reflects cultural beliefs and social values. A diagnosis is "constructed" in the interaction of patients and physicians, and of their respective representations of disease, in a given historical and social contex. The example of fibromyalgia has been chosen to illustrate this social construction of diagnostic categories.

Altered physical state of p210bcr-abl in tyrphostin AG957-treated K562 cells.

AG957 is a tyrosine kinase antagonist which prior studies had shown inhibits p210bcr-abl tyrosine kinase activity and K562 chronic myelogenous leukemia cell growth. We report here the effects of AG957 on the physical state of p210bcr-abl and its signaling adapter molecules Shc and Grb2 in K562 cells. After exposure to AG957, the amount of tyrosine-phosphorylated native p210bcr-abl decreases, with the appearance of a high molecular weight (> 210 kDa) p210bcr-abl. This effect is seen after [32P]orthophosphate and [35S]methionine labeling. Material suggesting the involvement of p210bcr-abl in high molecular weight complexes also appears using anti-Shc, anti-Grb2 and anti-phosphotyrosine antibodies. AG957 also acts in vitro to shift native p210bcr-abl in anti-p210bcr-abl or anti-Grb2 immunoprecipitates to higher molecular weight forms under conditions where the drug can also act as an antagonist of p210bcr-abl autokinase activity. Incubation with dithiothreitol inhibits the appearance of > 210 kDa forms of p210bcr-abl in the in vitro reaction. These results leads to the hypothesis that AG957 does not act simply as a reversible tyrosine kinase antagonist, but can alter the normal amounts and physical associations of molecules important in tyrosine kinase signaling. These effects likely reflect covalent cross-links induced by the drug.

Alterations in physical state and expression of human papillomavirus type 18 DNA following crisis and establishment of immortalized ectocervical cells

Integration of episomal human papillomavirus (HPV) DNA in infected cervical lesions during malignant progression is frequently observed, but the importance of integration is poorly understood. We have studied immortalization by HPV-18 of human cervical cells as an in vitro model system. Here, the status and expression of HPV-18 DNA in precrisis ectocervical keratinocytes was compared with that in the same cells after crisis and establishment of immortalization. Southern blots reserved, and two-dimensional gel analysis confirmed, that the precrisis culture contained more than 100 copies/cell of episomal HPV-18 DNA and no detectable integrated viral DNA. In contrast, the postcrisis cells contained a low copy number of only integrated viral genome. The Northern nlot patterns of E6-E7 and E2/E4 RNA expression were also different. Analysis of RNA by RT-PCR indicated that neither culture expressed the unspliced HPV-18 E6 oncogene present in tumor cell lines and that the precrisis, but not postcrisis, culture expressed the full-length E2 repressor. The two cultures displayed a similar keratinocyte morphology in vitro and a similar low grade dysplasia in vivo and both were non-tumorigenic. These results suggest that, although insufficient for complete malignant conversion, viral DNA integration during crisis is associated with the establishment of an immortalized phenotype in which HPV-18 DNA is integrated and HPV-18 RNA expression is altered.

Early hCG-induced desensitization of rat ovarian LH/hCG receptors is associated with altered physical state of membranes

Injection of pseudopregnant rats with pharmacological doses of hCG produced desensitization of adenylylcyclase and steroidogenic systems in ovarian membranes and luteal cells. Membrane lipid rigidity, as determined by fluorescence polarization of DPH, decreased as early as 0.5 h after injection of hCG. Desensitization also modified the differential scanning calorimetric profile characteristic of control membranes. The accessibility of ovarian LH/hCG receptors was unchanged. The results indicate that the hCG-induced decrease of membrane lipid rigidity is preceded by the process of desensitization of the rat ovary.

Vitamin E, membrane order, and antioxidant behavior in lung microsomes and reconstituted lipid vesicles

Vitamin E, a dietary antioxidant, is known to inhibit peroxidation of membrane lipids and to protect the lungs of vitamin E-deficient animals and to a lesser extent vitamin E-sufficient animals from oxidant injury. Since the protective interaction between vitamin E and biological membranes may be related to alterations in composition and physical state of membrane lipids, we evaluated the effect of vitamin E deficiency on lung microsomal lipids and membrane fluidity. Both intact microsomes and lipid vesicles prepared from the total lipid extracts of these microsomes were used. The percentage incorporation of vitamin E and cholesterol, membrane fluidity, and lipid peroxidation were measured in microsomes as well as their lipid vesicles. Fluidity was measured by monitoring changes in fluorescence anisotropy for 1,6-diphenyl-1,3,5-hexatriene (DPH). Lipid peroxidation was measured by thiobarbituric acid reaction. There were significant increases in the phospholipid ( p < 0.01), the total cholesterol ( p < 0.05), and the total saturated fatty acids ( p < 0.05) and decreases in total polyunsaturated fatty acid ( p < 0.01) content of vitamin E-deficient microsomes. There were no detectable peroxidative products in freshly isolated microsomes from either vitamin E-sufficient or -deficient lungs. However, lipids from vitamin E-deficient microsomal membranes were more susceptible to free radical initiated peroxidation than lipids from vitamin E-sufficient microsomes. Fluidity in vitamin E-deficient microsomes or in their lipid vesicles was significantly ( p < 0.05) decreased compared to the respective controls. In vitamin E-deficient microsomes or their lipid vesicles, the incorporation rate of vitamin E was two- to three-fold greater than in vesicles of vitamin E-sufficient microsomes or their lipid vesicles. However, the percentage incorporation of cholesterol was identical in both vitamin E-deficient and vitamin E-sufficient microsomes or in their respective lipid vesicles. As a result of vitamin E incorporation, fluidity was significantly decreased ( p < 0.05) in vitamin E-sufficient vesicles and was further decreased ( p < 0.001) in vitamin E-deficient vesicles. Incorporation of cholesterol also decreased fluidity in both vitamin E-deficient and vitamin E-sufficient vesicles but to the same extent ( p < 0.001). Lipid peroxide formation was two-fold greater in the vitamin E-deficient than in the vitamin E-sufficient vesicles. The increased incorporation of vitamin E (but not cholesterol) diminished ( p < 0.001) lipid peroxide formation in both vitamin E-deficient and vitamin E-sufficient vesicles. These results suggest that alterations in the physical state of membrane lipids in vitamin E deficiency favors incorporation of more vitamin E. Although both vitamin E and cholesterol decreased membrane fluidity, only vitamin E protects against membrane lipid peroxidation.

Drinking outcome expectancies among male alcoholics during relapse situations.

SummaryRecent research suggests that alcohol expectancies may affect drinking decisions and also predict relapse among alcoholics. In the present investigation, information on 22 alcoholics’expectancies regarding what alcohol would achieve for them in 31 discrete relapse situations was gathered. Results showed that almost half of the expectancies reported dealt with drinking as an aid in coping with a social situation. Another one‐quarter of the expectancies dealt with drinking to gain control of a situation, with the remainder divided between drinking to cope with a non‐social situation or to create an altered physical state. The majority (81%) of drinking outcome expectancies were characterized by the subjects as being achieved. Taken together, these data emphasize the importance of understanding alcohol expectancies in drinking situations.

Evidence for a membrane surface defect in erythrocytes in Huntington's disease

Electron spin resonance studies of erythrocyte membranes from patients with Huntington's disease and normal controls have been performed. Intact erythrocytes in each case were either untreated or subjected to proteolysis with the membrane impermeable enzymes, pronase, chymotrypsin, or trypsin. Membrane ghosts were prepared from untreated and protease-treated intact cells and spin labeled with protein- or lipid-specific spin probes. Comparison of the resulting electron spin resonance spectra confirmed our previous findings that in untreated samples the relevant parameter of the protein-specific spin label was increased in Huntington's disease (P < 0.02) suggesting an altered physical state of membrane proteins in this disorder, while no difference in erythrocyte lipid fluidity could be discerned. No significant difference in the physical state of membrane proteins in Huntington's disease and control as judged as spin labeling methods could be detemined in membrane ghosts prepared from protease-treated intact cells. These results, together with the known specificity of the proteases used in this study, suggest that a molecular defect in Huntington's disease erythrocytes is manifested in an exterior part of a membrane protein and supports our hypothesis that Huntington's disease is associated with a generalized cell membrane defect.

Phosphatidyl choline interaction with bovine serum albumin: Effect of the physical state of the lipid on protein-lipid complex formation

Radioactively labeled [ 14C]phosphatidyl choline dispersed on Celite was equilibrated with bovine serum albumin solutions buffered at pH 8.0. Phosphatidyl choline was rapidly solubilized in the presence of serum albumin, and formed stable protein-lipid complexes which were isolated by gel-filtration through a Sepharose 4B column. Under similar conditions, equilibration of the protein with phosphatidyl choline liposome dispersions in buffer did not result in complex formation. The altered physical state of phosphatidyl choline on the weakly adsorbing Celite surface appears to be essential for binding by native bovine serum albumin. This work reports the first observation of phosphatidyl choline binding to native serum albumin in bulk phase and suggests the possibility of exposing monodisperse lipids, under controlled conditions, to proteins having lipid binding properties.

Methamphetamine-induced alteration in the physical state of rat caudate tyrosine hydroxylase

Methamphetamine was found to induce a shift of a portion of rat striate (and not midbrain) tyrosine hydroxylase activity from the 11,000 g supernatant to the “synaptosomal” and “mitochondrial” particulate fractions with no change in total measurable enzyme activity, although the particulate enzyme demonstrated a greater affinity for the synthetic cofactor, 6,7-dimethyl-5,6,7,8-tetrahydropterin (DMPH 4). The magnitude of this shift appeared dose-related up to 5 mg/kg. It demonstrated a shortest latency of 10 min and a longest duration of 8 hr. It could not be produced in vitro by homogenizing the striate area in varying concentrations of methamphetamine or catecholamines. The effect could not be abolished by pretreatment with cycloheximide or intraventricular colchicine. It could not be induced by the administration of imipramine, footshock, electroconvulsive shock, or behaviorally activating intraventricularly-infused norepinephrine (NE). However, this change could be produced by the administration of α-methyltyrosine and reserpine. The ressrpine-induced change differed in that in addition to the shift of activity from the soluble to the particulate fraction, there was an increase in total measurable enzyme activity as well. It was suggested that a drug-induced reduction in intraneuronal catecholamines may be the common stimulus for the observed relative increase in rat caudate particulate tyrosine hydroxylase. The particulate state of caudate tyrosine hydroxylase generally resisted narrow clearance homogenization, hypotonic shock and sonication but varied in a complex way with varying ion concentrations (especially Ca 2 and Mg 2) in vitro. Varying membrane binding of soluble tyrosine hydroxylase via the manipulation in vitro of divalent cations led to apparent decreases in the specific activity of tyrosine hydroxylase. However, other recent studies in our laboratory have demonstrated that membrane binding of tyrosine soluble hydroxylase activates the enzyme allosterically for DMPH 4 binding as well as for the competitive inhibition of the affinity of this cofactor site by dopamine (DA) and norepinephrine (NE). It is within this context that the amphetamine-induced alteration in physical state of tyrosine hydroxylase assumes potential regulatory significance.

Psychopathology and 5-hydroxyindoleacetic acid excretion

Schizophrenics and nonschizophrenics do not differ in urinary excretion of 5-hydroxyindoleacetic acid on either a concentration or 24 h basis, nor do they differ in variability of excretion. Although a pattern was observed of decreasing psychopathology with increasing 5-hydroxyindoleacetic acid excretion, this pattern may be related to alterations in physical state accompanying psychopathology rather than to psychopathology per se.

Studies in trypanosomiasis II.—Observations on the red cell adhesion test

1. 1. We have shown that standard concentrations both of red cells and of trypanosomes are necessary in order to obtain constant results in the Red Cell Adhesion test. 2. 2. The character of adhesion obtained can be varied at will by altering the relative proportions of the various reagents or the time of incubation. 3. 3. Agglomeration and lysis of trypanosomes take place, in presence of homologous serum, when other conditions necessary for adhesion are not present, e.g., an unsuitable indicator (red cells or bacteria). 4. 4. The necessity for the presence of complement in this test has been confirmed and it is shown that the absence of any single component of complement inhibits the reaction. 5. 5. The end titre of an immune serum has shown only slight variations when repeatedly examined by the adhesion test. 6. 6. Certain human red cells will not adhere to sensitized trypanosomes. 7. 7. This condition is met with both in pathological conditions and in normal individuals. We have been unable to correlate it with any altered physical state of the red cell. 8. 8. In the same way certain bacteria adhere to be sensitized trypanosomes and others fail to do so. This is not correlated with rough and smooth states of the culture.