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Freeze-drying of cephalothin sodium: granularly agglomerated crystallization during freezing. II.

The mechanism of granularly agglomerated crystallization during freezing of cephalothin sodium (CET-Na) in aqueous solution has been discussed. Our previous report noted that strict control of the following is important in order to obtain crystalline granular agglomerates of CET-Na: (1) thermal history of the solution before receiving freezing, (2) cooling rate in freezing, and (3) aging temperature level in the crystal growth step. In order to clarify the physico/chemical meanings of the individual controls, further investigations have been made: 1) with varying thermal history, aqueous 30-% CET-Na solutions were prepared for storage, first at 0 degrees C with its supersaturation and secondly at 25 degrees C, in an unsaturated state for observing any structural changes by viscosimetry, refractometry, and surface tensiometry; 2) morphological changes in ice crystals during freezing at varying cooling rates, as well as those during the crystal growth step, were observed by polarized-light cryomicroscopy and scanning electron microscopy; 3) melting, as well as crystal growth, at several aging temperature levels were observed by electrical conductometry and also by the above-mentioned techniques.(ABSTRACT TRUNCATED AT 250 WORDS)

Cephalothin↗

[Crystallization and subsequent freeze-drying of cephalothin sodium by seeding method].

Cephalothin sodium (CET-Na) in crystals can be obtained by freezing the aqueous solution and subsequent warming at a fixed temperature for facilitating crystallization prior to vacuum application for drying. The product has, however, been found to unavoidably contain traces of the amorphous CET-Na, which causes a rapid color development during storage. By using thermal analysis, differential scanning calorimetry (DSC), electric conductometry, and polarized light cryomicrographic techniques, the solubilities in water, freezing point, eutectic point, and melting behavior of CET-Na in aqueous solution were investigated. The investigation demonstrated that CET-Na in supersaturated aqueous solution is very stable, and that seeding with microcrystalline CET-Na to the supersaturated solution and subsequent cooling of the mixture till its freezing point gives neither any evidence for crystallization nor for growth of the seed crystals. The freeze-drying of CET-Na in the supersaturated solution after seeding has been demonstrated to give crystalline CET-Na containing neither of amorphous nor of quasi-crystalline form.

Cephalothin↗

[Behaviors of nitrato complexes of nitrosylruthenium in aqueous solutions (author's transl)].

Nitrato nitrosylruthenium complexes [RuNO(NO3)x(H2O)5-x] (3-x)+ readily dissociate in aqueous solutions with decrease in pH and increase in electrical conductivity of the solutions. This study aimed to elucidate the behaviours of dissociation of the complexes with time. The change in the amount of undissociated complexes was determined with time. The results indicated that the dissociation was a multi-order reaction involving both protolysis and hydrolysis. The protolysis completed in relatively short period within(several tens of minutes), but it depended on the concentration of the complexes in the solution. The completion of the protolysis and the formation of the resulting dissociation products were observed by absorption spectrometry. The dissociation products, which were assumed as aquohydroxy complexes, underwent the successive step-wise dissociation for a prolonged period as revealed by pH measurements. The rate constants involved in the step-wise dissociation, process were obtained. The degree of dissociation and dissociation constant of the complexes were measured by conductometry.

Chemical Phenomena↗

[Physico-chemical properties of borate derivatives of DOPA, dopamine, and their liposome forms].

To increase the solubility of L-3,4-dihydroxyphenylalanine (DOPA) and dopamine (DA) incorporated in liposomes, it was suggested to convert them into ammonium and 1-adamantylammonium borate complexes. The structure of these complexes was studied by 11B and 1H NMR, IR, and mass spectrometry and conductometry. The liposomic form of the complexes is characterized by a high active compound/lipid molar ratio (0.5). Catechols in the form of complex salts are retained better within the inner volume of liposomes.

Amantadine↗

[Anomalous change in the specific conductivity in lipoproteins at around physiologic temperatures].

Studying the temperature dependence of conductivity sigma of rat and human lipoproteins and apoprotein A-I fractions revealed an anomalous region in the range of temperatures (35-38) +/- 0.5 degree C. The activation energy delta H and temperature coefficient sigma (delta sigma/delta T) on both sides of Tc and the heat of transition (delta H of transition) were calculated. In high-density human lipoproteins and apoA-I, the delta H value was found to be very low. Some mechanisms of interaction of hydrocortizone with high-density lipoproteins and apoA-I were studied by using IR-spectroscopy and conductometry were studied. It was found that the hormone considerably increases the portion of alpha-helices and beta-structures in these proteins (coil<-->alpha-helix and coil<-->beta-structure transitions). In this case, delta H value of the transition increases 13-fold; in addition, the abnormal region in apoA-I shifts 1-2 degrees C downwards. The anomalous changes in conductivity in the range of physiological temperatures in all lipoprotein fractions including apoA-I are probably related to structural phase transitions both in proteins and in phospholipids. Since the delta H value of the transition in human high-density lipoproteins is small, it is assumed that, in phospholipids of these particles, an orientation transition of the A<-->C smectic type takes place, which is assigned to the second-order phase transition. The structural transition in apoA-I can probably also be assigned to the second-order phase transition since the enthalpia of the transition is very small; presumably, this transition is related to changes in symmetry due to changes in the secondary structure (coil<-->beta-tructure transition).

Animals↗

Interactions between chitosan and glycosaminoglycans (chondroitin sulfate and hyaluronic acid): physicochemical and biological studies.

Chitosan is a polysaccharide well known for its numerous and interesting biological properties, indeed, it is a biocompatible, bioresorbable and bioactive biopolymer. It is therefore often introduced in the human body, where it happens to be in contact with glycosaminoglycans (GAG's), especially chondroitin sulfates and hyaluronic acid which play important part in living media. Thus it seems interesting to consider systems associating chitosan and GAG's. The aim of our work is to study the mechanism of formation of biomaterials constituted of chitosan and GAG's which could have interesting biological properties such as improving the wound-healing acceleration and the cellular assistance for skin and cartilage recovery. In the same time, it was interesting to try to understand what can happen when chitosan is introduced in a natural surrounding containing GAG's. In a first part, the complexes between chitosan and GAG's were characterised by various physicochemical techniques: pH-metry, conductometry and Infra-red spectrometry. They appeared to be polyelectrolyte complexes obtained by the formation of polyanion-polycation interactions held between ammonium functions of chitosan and carboxylate and/or sulfate groups of GAG's. The complexes formed are very strong and can, in some cases, even conduct to the deprotonation of carboxylic functions. In a second part we considered the biological properties of the complexes previously obtained. The hydrolysis activity in presence of specific enzymes was investigated. We also studied the cytocompatibility of chitosan alone and its complexes with the two considered GAG's toward two kinds of cells (chondrocytes and keratinocytes). At the end of the work, a short animal experimentation on rats was performed allowing the comparison between in vitro and in vivo results.

Animals↗

[Electrical resistance of cerebrospinal fluid in inflammatory diseases of central nervous system in children (author's transl)].

The specific electrical resistance of the cerebrospinal fluid was measured by means of conductometry in 14 cases of meningitis purulenta, 17 cases of meningitis serosa, 10 cases of encephalitis and in 32 control subjects. The mean value was found to be significantly increased in meningitis purulenta in comparison to the control group. The differences between the average values of the electrical resistance concerning other groups studied were found to be unsignificant. In some cases the initially increased electrical resistance of cerebrospinal fluid observed in the acute state of the disease reached the normal levels at the time of clinical improvement. The presumable causes of these phenomena are discussed.

Central Nervous System Diseases↗

[The aquation of oxaliplatin and the effect of acid].

AIM: To investigate the aquation of oxaliplatin in aqueous solution at different temperatures and gain the kinetic data. METHODS: Electronic conductometry and high performance liquid chromatography (HPLC) were used to measure the oxaliplatin content in the reaction systems at different time. RESULTS: The aquation of oxaliplatin followed a pseudo-first-order rate law. In the absence of H+, the observed rate constant kobs was 7.76 x 10(-6).min-1 and the half life t1/2 was 62 days at 25 degrees C. In the presence of H+, the aquation could be accelerated by H+ according to the equation kobs = (2.61 + 21.9 [H+]) x 10(-4).min-1. The mechanism of aquation has also been proposed in this paper. From the mechanism, the rate of aquation following to r = (k1 k2) [l-OHP]/k-1 in the absence of H+ and r = (k1 + K0k3 [H+]) [l-OHP] in the presence of H+ have been deduced, which were in perfect agreement with the experimental results. CONCLUSION: In the absence of H+, the aqueous solution of oxaliplatin is stable, which meets to the request of clinical.

Acids↗

[Rapid laboratory detection of antigens of infective agents of infections and technical means for their realization].

A system of new accelerated and rapid methods for the detection of the antigens of the infective agents of plague, cholera, tularemia and brucellosis were developed on the basis of solid phase immunosuspension tests: the passive hemagglutination (PHA) test and the latex agglutination (LA) test. The immunological and physico-chemical properties of suspensions in the PHA and LA tests made it possible to use extraneous sources of energy (centrifugal acceleration and the electric field) to accelerate these tests. The results of the PHA and LA tests were registered with the use of a densitometer, model Ultrascan 2202, and a tester, model C 34014.2. To apply centrifugal acceleration and the electric field, a laboratory centrifuge and an electrophoretic microchamber were designed. Densitometry was carried out on modified plates and conductometry, with the use of modified electrodes. The time of obtaining the results of the PHA and LA tests was 15-30 minutes with the use of centrifugation and 2-5 minutes in the electric field, which made it possible to regard these tests as rapid.

Antigens, Bacterial↗

Stability of the complexes of some lanthanides with coumarin derivatives. I. Cerium(III)-4-methyl-7-hydroxycoumarin.

A complex of cerium(III) with 4-methyl-7-hydroxycoumarin was synthesized by mixing water solutions of cerium(III) nitrate and 4-methyl-7-hydroxycoumarin sodium salt in a metal-to-ligand molar ratio of 1:2. The complex was characterized and identified by elemental analysis, conductometry, IR, 1H and 13C NMR-spectroscopy, mass spectral data, DTA and TGA. Thermal analysis of the complex indicated the formation of a compound of the composition CeR2(OH).5H2O, R standing for the ligand. The reaction of cerium(III) with 4-methyl-7-hydroxycoumarin was studied in detail by the spectrophotometric method. The stepwise formation of two complexes, vis., CeR2+ and CeR2+, was established in the pH region studied. The equilibrium constants for 1:1 and 1:2 complexes were determined to be 10.72 and 9.22, respectively.

Algorithms↗

[Properties of benzethonium chloride in micellar solutions and the effect of added sodium chloride].

Aqueous solutions of the antimicrobially effective quaternary ammonium salt benzethonium chloride (hyamine 1622) were studied using UV spectrophotometry and partially conductometry. The spectra of micellar solutions of benzethonium chloride revealed a concentration-dependent bathochromic and hyperchromic shift of a weak UV absorption band in the region 250-300 nm. This served to elaborate the spectrophotometric determination of the critical micellar concentration (CMC) of benzethonium chloride and the concentration of free benzethonium cations in micellar solutions without an addition of NaCl and with a constant addition of NaCl 0.003, 0.1 and 0.15 mol/l. Premicellar associations were not observed and in NaCl-free solutions CMC 0.0028 mol/l was spectrophotometrically determined. An addition of NaCl resulted in an increased hyperchromic effect and strengthening of micellization, manifested by a more than ten-times decrease in the CMC as well as the concentration of free benzethonium cations in micellar solutions. The courses of the determined concentrations of free benzethonium cations in the solutions both without and with the presence of NaCl were quite similar; their maximal values were always just a little higher than the corresponding CMC and with a further growth of the total concentration of benzethonium chloride there was, on the other hand, a marked decrease in the concentration of its free cations in micellar solution. Possible effects of a decreased concentration of free benzethonium cations due to an added electrolyte on antimicrobial activity and formation of ionic pairs are discussed.

Anti-Infective Agents↗

[Analysis of solutions for parenteral use under field conditions].

Methods for determination of relative density, osmolarity, then refractometry, polarymetry and conductometry as simple methods suitable for work under field conditions have been applied for the quality control of the following solutions for infusion and injections: glucose, mannitol, sodium chloride, sodium hydrogencarbonate, magnesium sulphate and potassium chloride. The results obtained in the analysis of preparations have shown the advantage of refractometry.

Infusions, Parenteral↗

Influence of moxaverine hydrochloride on membrane curvature and microsieve filterability of red cells after exposure to hyperosmolarity and lactacidosis.

Using a combination of novel techniques to assess quantitatively the shape and the filterability of red blood cells (RBC) after exposure to stress conditions (400 mosmol/l, lactacidosis, pH 6.8), the effects of 1-benzyl-3-ethyl-6,7-dimethoxy-isoquinoline hydrochloride (moxaverine-HCl, Kollateral) were tested. The shape of freely suspended RBC was quantified using the tangent count procedure. The filterability (microrheological performance) of leukocyte-free RBC suspensions was determined by computer-assisted conductometry using novel precision metal microsieves with uniform pore diameter of 4.2 micron. Moxaverine, when present in doses between 10(-5) und 10(-2) mol/l while the RBC are stressed, restored both the normal discoid red cell configuration and the microrheological performance when tested under low shear stresses. The data show that moxaverine, a papaverine derivative, hitherto considered as a classical vasodilator exerts protective effects on RBC membrane curvature and whole cell microrheological behavior (performance). The protective effects manifest themselves when the RBC's are exposed to abnormal biochemical conditions such as they might occur in poststenotic areas, where hypoxic ischemia is known to lead to a combination of hyperosmolarity and lactacidosis which modify the RBCs.

Acidosis, Lactic↗

[Effect of intestinal circulation on the osmotic balance between the intestinal lumen and blood in awake rats].

Total electrolyte concentrations in portal vein and aortic blood of unanesthetized rats were measured continuously by means of ultrafiltrate conductometry. Portal flow rate and mesenteric venous pressure (pmes) could also be measured. The last could be raised to any desired level by a specially developed portal vein clamp. Intraduodenal injections of water (0.5 or 1% BW) were given in a first series of experiments with and without sham-attacking (activating) the animal for 10 s and in a second series with and without raising pmes. Portal flow rate dropped in both cases. But whereas activation led to a decrease in the concentration changes in the v. portae and in arteriovenous differences, a rise in pmes had the opposite effect. Comparison of the total free water change in the v. portae (Mpo) with the quantity of water given (MH2O) revealed that Mpo/MH2O dropped in both series of experiments, provided that pmes was not increased by much more than 2 mm Hg (portal flow did not decrease much under normal). The differing results were explained by taking into account the specificities of blood circulation in the gut wall. The experiments have shown that even transient obstruction of gut tissue perfusion can delay dissipation of concentration imbalance between the gut and parenteral space, thus having adverse effects on the gut cells.

Animals↗

Functional analyses of the stratum corneum in scars. Sequential studies after injury and comparison among keloids, hypertrophic scars, and atrophic scars.

OBJECTIVE: To characterize the functional properties of the stratum corneum (SC) of various scars. DESIGN: A prospective cohort study. SETTING: University hospital medical center. PATIENTS: Thirty-two consecutive patients surgically treated for various skin diseases and 26 consecutive patients with hypertrophic scars or keloids. MAIN OUTCOME MEASURES: Noninvasive bioengineering measurements of functional properties of the SC, such as transepidermal water loss (TEWL), high-frequency conductance, and SC turnover time. RESULTS: The SC barrier function assessed by TEWL was found to be a better parameter for the functional evaluation of scars than the hydration state of the skin surface measured by high-frequency conductometry. In general, the SC on the scars of deeper wounds in the dermis took longer to normalize functionally than the SC on the scars of superficial wounds, especially on the high compared with the abdomen. Thus, elevated levels of TEWL observed on scars at the donor sites of split-thickness grafts normalized between 200 and 400 days in contrast to fewer than 50 days for those of subepidermal erosions. Both TEWL and high-frequency conductance remained high in hypertrophic scars and keloids, and the SC involved showed a faster turnover time than that of adjacent normal skin. CONCLUSIONS: Scars, a proliferative change of the dermis, can be objectively evaluated according to functional abnormalities of the SC, because the dermis has a close relationship with the epidermis and with the SC. The functional characteristics of the SC of fresh scars and those of hypertrophic scars and keloids resemble those of retinoid-treated skin, rather than those found in epidermal hyperproliferative conditions such as psoriasis and dermatitis.

Abdomen↗

[Flow cytometry in hematology. Methods and technique of flow cytometric analysis].

Reviews the history of flow cytometry, the philosophy of the method, main methods of cell investigation (conductometry, registration of light absorption and diffusion, cytofluorometry, study of fluorescence polarization, and analysis of a wave-shaped signal). Describes the equipment and methods for flow cytofluorometric analysis of cells, used in hematology. Characterizes the hematological analyzers with differentiated estimation of leukocytes.

Animals↗