Biomedical subjects

R Vargas

Publications and source records attributed to R Vargas.

At least 73 records · Page 4Linked to original sources

PubMed1993

Cubic phases of lipid-containing systems. Elements of a theory and biological connotations.

It has recently been shown that the structure of two of the six cubic phases so far identified in lipid-containing systems is micellar, one (Q223) of type I, the other (Q227) of type II. The micelles of both phases belong to two distinct classes, those of each class being centred at one of the special positions of the space group. From the chemical viewpoint, phase Q227 seems to require a heterogeneous mixture of water-miscible and water-immiscible lipids, whereas phase Q223 has been observed with chemically pure lipids. Also, the area/volume ratio measured at the polar/apolar interface takes the same value in the two types of micelles of phase Q223, different values in those of phase Q227, in keeping with the notion that the area/molecule ratio is closely related to the chemical activity of the lipid components. The topological properties of the micellar phases are profoundly different from those of the bicontinuous phases. The bicontinuous cubic phases (Q230, Q224, Q229) are often presented as paradigms of the infinite periodic minimal surfaces (IPMS). Some authors have generalized that notion and sought in the IPMS a unified theory underlying the entire field of lipid polymorphism. These analogies entertain some confusion between the mathematical concept of surface and the physical notion of interface. A few electron density maps are presented to document the distance that separates the polar/apolar interfaces from the IPMS. The maps also show that some of the geometric singularities (points, lines, surfaces) of the structures coincide with the locus of the CH3 ends of the chains and with the very centre of the water matrix, i.e. with the regions where the short-range disorder is highest. We introduce the expression chaotic zones to designate these regions. In all the lipid phases the chaotic zones are found to occupy special geometric positions, either related to the symmetry elements or to the IPMS. It thus appears that it is energetically more advantageous to adopt an orderly disposal of the short-range disorder than to minimize the area of the polar/apolar interfaces. Finally, regarding the possible biological significance of lipid polymorphism, the point is stressed that among the phases that are observed in equilibrium with excess water (these phases are also the most likely candidates for a biological role) those with a cubic symmetry deserve special attention.(ABSTRACT TRUNCATED AT 400 WORDS)

Lipids↗

PubMed1993

Can garlic reduce levels of serum lipids? A controlled clinical study.

PURPOSE: To assess the effects of standardized garlic powder tablets on serum lipids and lipoproteins, glucose, and blood pressure. SUBJECTS AND METHODS: Forty-two healthy adults (19 men, 23 women), mean age of 52 +/- 12 years, with a serum total cholesterol (TC) level of greater than or equal to 220 mg/dL received, in a randomized, double-blind fashion, either 300 mg three times a day of standardized garlic powder in tablet form or placebo. Diets and physical activity were unchanged. This study was conducted in an outpatient, clinical research unit. RESULTS: The baseline serum TC level of 262 +/- 34 mg/dL was reduced to 247 +/- 40 mg/dL (p < 0.01) after 12 weeks of standard garlic treatment. Corresponding values for placebo were 276 +/- 34 mg/dL before and 274 +/- 29 mg/dL after placebo treatment. Low-density lipoprotein cholesterol (LDL-C) was reduced by 11% by garlic treatment and 3% by placebo (p < 0.05). There were no significant changes in high-density lipoprotein cholesterol, triglycerides, serum glucose, blood pressure, and other monitored parameters. CONCLUSIONS: Treatment with standardized garlic 900 mg/d produced a significantly greater reduction in serum TC and LDL-C than placebo. The garlic formulation was well tolerated without any odor problems.

Adult↗

PubMed1993

Oestradiol inhibits smooth muscle cell proliferation of pig coronary artery.

1. The effect of oestradiol 17 beta on vascular smooth muscle proliferation was examined in segments of the pig left anterior descending coronary artery (LAD). It was established by cytochemical techniques that out-growth from the segments was composed of vascular smooth muscle cells. 2. [3H]-thymidine uptake by pig LAD segments was used as an index of vascular smooth muscle cell proliferation. Nitroprusside and forskolin significantly inhibited [3H]-thymidine uptake and were used as positive controls. 3. Oestradiol 17 beta (180-360 nM) inhibited thymidine uptake by pig LAD segments (P < 0.05). The inhibition was observed only in the absence of phenol red, which is a weak oestrogen receptor agonist. The anti-oestrogens tamoxifen and its more potent metabolite 4-hydroxytamoxifen, both of which are partial oestrogen receptor agonists, also significantly inhibited thymidine uptake. However, pretreatment with either tamoxifen or 4-hydroxytamoxifen did not significantly block oestradiol 17 beta-induced inhibition of thymidine uptake. 4. The LAD segments bound [3H]-oestradiol 17 beta in a time-dependent manner and about 20 to 30% was displaced by an excess of unlabelled oestradiol 17 beta. Autoradiography showed [3H]-oestradiol 17 beta was evenly distributed in the cytosol and nuclei of cells in the three layers of the vessel wall. 5. The data suggest that oestradiol 17 beta inhibits smooth muscle cell proliferation in porcine LAD segments, possibly through an oestrogen receptor mechanism. This in vitro effect suggests an in vivo role for oestradiol 17 beta in directly protecting coronary arteries against myointimal proliferation in premenopausal women.

Actins↗

PubMed1993

Epidemic cholera in the Amazon: the challenge of preventing death.

Epidemic cholera struck Peru in January 1991, and spread rapidly. The national cholera case-fatality rate (CFR) was less than 1% in the first six months of the epidemic, but in some rural areas, the CFR exceeded 10%. We investigated cholera mortality in the rural Amazon region, an area with a CFR of 6.3%. We conducted a case-control study, comparing 29 decedents with 61 survivors of recent cholera-like diarrheal illness in 12 villages with a combined CFR of 13.5%. Of 29 decedents, 28 (96%) died in the village or en route to a health facility. Death occurred within 36 hours of illness onset for 83% of the decedents. In 11 (92%) villages, the first or second recognized case was fatal. Death was associated with receiving treatment only at home (odds ratio indeterminate; 95% confidence interval 3.5, indeterminate). Treatment with oral rehydration salts (ORS) was not protective against death for patients who received treatment only at home. Treatment with homemade sugar-salt solution (SSS) was also not protective; fewer than one-third of respondents knew the correct SSS recipe. Most decedents experienced multiple barriers to health care. Cholera victims died rapidly and early in village outbreaks, and few patients had access to health care. Provision of threatened villages with ORS supplies and education in their use before cholera strikes is essential to reducing cholera mortality in this region.

Adolescent↗

PubMed1992

Order-disorder phenomena in myelinated nerve sheaths. IV. The disordering effects of high levels of local anaesthetics on rat sciatic and optic nerves.

Sequences of 15 minute X-ray scattering spectra were recorded with rat sciatic and optic nerves, superfused with tetracaine-containing Ringer solutions. The spectra were analysed using the algorithm advocated in this series of papers. The main results, as a function of the time of exposure to tetracaine, were: the mean value of the repeat distance increases; its variance decreases; the average number of membrane pairs per coherent domain decreases; the fraction of isolated membrane pairs increases. Eventually, the spectra were observed to give way to the continuous intensity curve of a single, isolated membrane pair. At all stages of the experiment the continuous intensity curves were found to differ from one type of nerve to the other, and to be invariant, for each type of nerve, with respect to the tetracaine treatment. The X-ray scattering study clearly identified the nature of the structural differences between the two types of myelin sheaths: in that of native sciatic nerves, packing disorder preferentially affects the cytoplasmic space of the membrane pair, and tetracaine disrupts the packing in that space; in the myelin of optic nerves it is the external space that is preferentially affected by packing disorder and disrupted by tetracaine. The time-course of the structure parameters showed that, at any stage of the experiment, tetracaine acts preferentially on the more highly disordered regions of the structure and totally disrupts them. These results corroborate earlier conclusions reported in the previous papers of this series. An electron microscope study was also performed on tetracaine-treated nerves: the results, in close agreement with those of the X-ray scattering study, neatly confirm the conclusions given above. In a more general way, the remarkable agreement between the results of the analysis of the X-ray scattering spectra and the electron microscope observations strongly supports the validity of the physical model used in this series of papers and the correctness of the mathematical treatment that we advocate. Finally, the relations between this work and the work of others are discussed. It must be stressed that the present work bears on the toxic rather than on the anaesthetic effects of tetracaine.

Action Potentials↗

PubMed1992

Cubic phases of lipid-containing systems. The structure of phase Q223 (space group Pm3n). An X-ray scattering study.

The hexagonal (H) and the cubic (Q223) phases of the systems dodecyltrimethylammonium chloride-water and palmitoyllysophosphatidy choline-water have been studied by X-ray scattering techniques. The signs of the reflections of phase H were determined by a systematic study as a function of the water content, those of phase Q223 were assessed using a pattern recognition approach based upon the axiom that the histograms of the electron density maps of phases Q223 and H, extrapolated to the same concentration and properly normalized in scale and shape, are very similar to each other. In the case of phase Q223, all the sign combinations (the phi-sets) compatible with the observed reflections were generated, and each of the corresponding histograms was compared with the histogram of the map of phase H. One novelty of this work is the use of a highly sensitive criterion to estimate the similarity of the histograms, namely the distance in the six-dimensional space of the moments [mean value of (delta rho)n]1/n, for 3 greater than or equal to n greater than or equal to 8. In the two systems, the use of this criterion has led to the unambiguous choice of one electron density map. The maps show that the structure of phase Q223 consists of disjointed micelles (of type I), belonging to two different classes: those of one class are quasi-spherical in shape and are centered at the points a, those of the other class are disc-shaped and are centred at the points c. The results of this work rule out a structure formed by a cage-like distribution of rods enclosing a set of quasi-spherical micelles and is consistent with previous proposals. This is the second example, after that of phase Q227, of a micellar cubic phases in lipid-containing systems; all the known examples of phase Q223 are of type I, those of phase Q227 of type II.

Freeze Fracturing↗

PubMed1992

Lipid polymorphism: a correction. The structure of the cubic phase of extinction symbol Fd-- consists of two types of disjointed reverse micelles embedded in a three-dimensional hydrocarbon matrix.

The X-ray scattering study of a cubic phase of extinction symbol Fd--, recently performed on a lipid extract (PFL) from Pseudomonas fluorescens [Mariani et al. (1990) Biochemistry 29, 6799-6810] has been extended to several other systems, all consisting of mixtures of water-miscible (MO, PC, PE, oleate) and of water-immiscible (FA, DG) lipids, plus water. In all of these systems the cubic phase was observed in the presence of excess water. Some inconsistencies observed between PFL and the other systems, the fact that in PFL one of the reflections of the cubic phase happened to coincide with the strongest reflection of the hexagonal phase, and the finding, in one of the original cubic samples of PFL kept in the cold for more than 3 years, that the intensity of one of the reflections had decreased dramatically all indicated that a nonnegligible amount of a hexagonal impurity was in fact present in the samples of PFL originally thought to contain a pure cubic phase. The intensities were corrected for that impurity and analyzed again using a pattern recognition approach based upon the axiom that the histogram of the electron density maps is invariant with respect to physical structure, when different phases are compared whose chemical composition is the same. The hexagonal phase provided the reference phase for the comparison. The moments mean value of (delta rho)n were used to compare the histograms.(ABSTRACT TRUNCATED AT 250 WORDS)

Crystallography↗

PubMed1992

Human liver protein map: a reference database established by microsequencing and gel comparison.

This publication establishes a reference human liver protein map obtained with immobilized pH gradients. By microsequencing, 57 spots or 42 polypeptide chains were identified. By protein map comparison and matching (liver, red blood cell and plasma sample maps), 8 additional proteins were identified. The new polypeptides and previously known proteins are listed in a table and/or labeled on the protein map, thus providing a human liver two-dimensional gel database. This reference map can be used to identify protein spots on other samples such as rectal cancer biopsies.

Amino Acid Sequence↗

PubMed1992

In vitro effect of oestradiol on thymidine uptake in pulmonary vascular smooth muscle cell: role of the endothelium.

1. The effect of different concentrations of oestradiol-17 beta (3-300 nM) on [3H]-thymidine uptake was studied in segments from canine pulmonary artery, and cultures of rat pulmonary vascular smooth muscle cells (VSMC). 2. Incubation with oestradiol-17 beta for 24 h, potentiated in a concentration-dependent manner [3H]-thymidine uptake in VSMC cultures. 3. Oestradiol-17 beta potentiated thymidine uptake by pulmonary arterial segments but only when the endothelium had been removed. Autoradiography showed dense incorporation of radioactive thymidine in the vascular smooth muscle cells of the media. 4. The non-steroidal oestrogen, stilboestrol (300 nM), also significantly potentiated [3H]-thymidine uptake, in both VSMC cultures and pulmonary artery segments. Testosterone was ineffective at a similar concentration. 5. Pre-incubation of the pulmonary VSMC with the anti-oestrogen tamoxifen (1 microM) antagonized the potentiating effect of oestradiol-17 beta on [3H]-thymidine incorporation. The effect of tamoxifen was less pronounced in pulmonary arterial segments. 6. These data suggest that oestrogen may promote proliferation of pulmonary VSMC. Endothelial injury or dysfunction may be an important factor in the expression of the oestrogenic effect. 7. We speculate that plasma oestrogen may be a contributing factor to the proliferative lesion observed in certain forms of pulmonary vascular injury in women.

Animals↗

PubMed1992

Safety and pharmacokinetics of multiple doses of intravenous ofloxacin in healthy volunteers.

The safety and pharmacokinetics of ofloxacin in 48 healthy male volunteers were studied in a two-center, randomized, double-blind, placebo-controlled study. Ofloxacin (200 or 400 mg) or placebo was administered as 1-h infusions every 12 h for 7 days. Plasma ofloxacin concentrations were measured by high-performance liquid chromatography. Mean harmonic half-lives ranged from 4.28 to 4.98 h in the 200-mg dosing group and from 5.06 to 6.67 h in the 400-mg dosing group. Intragroup comparisons of trough plasma concentration-versus-time data from study days 2 through 7 revealed that steady state was achieved by day 2 of both multiple-dose regimens. Intergroup comparisons of mean harmonic half-lives, the areas under the concentration-time curve from 0 to 12 and 0 to 60 h, clearance, and apparent volume of distribution (area method) revealed that the pharmacokinetics of ofloxacin are dose independent. Both ofloxacin dosage regimens appeared to be reasonably well tolerated. The two dosage regimens of ofloxacin, 200 or 400 mg every 12 h, appear to be safe and provide serum drug concentrations in excess of the MICs for most susceptible pathogens over the entire dosing interval.

Adolescent↗

PubMed1991

Order-disorder phenomena in myelinated nerve sheaths. III. The structure of myelin in rat optic nerves over the course of myelinogenesis.

An X-ray scattering study was performed on optic nerves dissected from rats aged from ten days to one year. The spectra were analysed using the procedure described in the previous papers of this series. Each experiment yields the values of a variety of parameters: the average D and the variance sigma D of the repeat distance, the average number mean value of N of motifs per crystallite, the fraction alpha loose of myelin that does not belong to the compact sheaths, the sets [idiff(h/D)] and [imotif(k/2D)] that suffice to define, respectively, the spurious scattering and the continuous intensity curve of the elementary membrane pair. A surprising result is that, in the native optic, as previously found in the swollen sciatic nerves, the stacking disorder affects the external space, whereas in native sciatic nerves the disorder affects the cytoplasmic space. An analysis of the evolution of the structure parameters as a function of the age of the animal and a comparison with the results previously obtained with rat sciatic nerves led to the following conclusions: the structure of the elementary membrane pair is constant throughout myelinogenesis; mean value of N is much smaller in optic than in sciatic nerves; mean value of N and the degree of myelination increase with age in the two types of nerve; D is smaller in optic than in sciatic nerves; in optic nerves, D decreases slightly with age, but in sciatic nerves it increases; sigma D is strongly age-dependent in optic nerves, but almost age-independent in sciatic nerves. In contrast to sciatic, the structure of optic nerve myelin was found to be almost insensitive to hypertonic solutions. Finally, a pair of electron density profiles was selected, quite similar to those selected previously in sciatic nerves, one corresponding to Caspar & Kirschner's the other to Worthington & McIntosh's proposals, neither of which can be ruled out according to the criteria used in this work.

Aging↗

PubMed1991

A new clinical bioassay for antipyresis.

Three studies that describe antipyretic bioassay are detailed. Reference Standard Endotoxin (RSE) was used to induce fever in healthy male volunteers under randomized, single-dose, double-blind, parallel, and standard drug-control conditions. Thirty minutes before administering RSE, the subjects were medicated with test drug, and oral temperatures were recorded every 15 minutes for 6 to 8 hours. Two NSAIDs and a centrally acting analgesic were evaluated. Both doses of a propionic derivative, three high doses of tebufelone (a new NSAID), as well as the high dose of flupirtine effectively obtunded the fever response to RSE. Adverse reactions consisting of flu-like symptoms such as myalgia, headache, and chills were also significantly reduced with the standard as well as test drugs. The authors conclude that the RSE model is a quick, safe, and reliable method to evaluate antipyresis and to predict other pharmacologic effects of these types of drugs, such as analgesia.

Adult↗

PubMed1991

Antipyretic activity of tebufelone (NE-11740) in man.

Tebufelone (formerly NE-11740) is a member of the new class of di-tert-butyl-phenol anti-inflammatory agents. It has previously been reported that this new agent has potent analgesic, antipyretic, and anti-inflammatory effects using in vitro, in vivo, and ex vivo experimental models. A randomized, active- and placebo- controlled double-blinded study in 120 healthy males, 20 to 55 years old, was conducted to clinically assess tebufelone's antipyretic activity. Subjects received a single peroral dose of placebo, 650 mg aspirin (ASA), or tebufelone at doses of 25, 50, 100, or 200 mg. Thirty minutes later, E. coli endotoxin (2 ng/kg) was administered intravenously. Oral temperatures were recorded at 15 minute intervals from 30 minutes post dosing to 8 hours post endotoxin administration. Areas under the temperature curves (AUCs), adjusted for baseline, were significantly lower than placebo for ASA and all but the 25 mg tebufelone groups. An AUC dose-response equation estimates 60 mg tebufelone as equivalent to 650 mg ASA, with 50 mg tebufelone not significantly greater than 650 mg ASA. Side effects, attributable to the endotoxin, included mild flu-like symptoms and were worse in the placebo group and the non-efficacious 25 mg tebufelone group. Doses of 100 and 200 mg tebufelone had onset characteristics indistinguishable from 650 mg ASA, whereas 50 mg tebufelone showed significantly slower onset while suppressing temperature for a longer period than ASA. These results provide an important early demonstration of tebufelone's biological activity in man.

Adult↗

PubMed1991

A multicenter comparison of the safety and efficacy of isradipine and enalapril in the treatment of hypertension.

This multicenter trial compared the efficacy and safety of isradipine and enalapril in 160 patients with essential hypertension. Patients received isradipine or enalapril for 10 weeks after a placebo wash-out period of three to five weeks. Dosage was titrated for six weeks on the basis of blood pressure (BP) response and was then maintained for the remainder of the study. Isradipine reduced systolic and diastolic BP by 12 and 9 mm Hg, respectively, and enalapril by 10 and 7 mm Hg, respectively (between-treatment difference P less than .05 for diastolic BP). Overall, isradipine resulted in a higher responder rate, particularly among patients who had higher entry BPs. Fifteen enalapril-treated patients and four isradipine-treated patients discontinued treatment (four taking enalapril and none taking isradipine withdrew because of lack of efficacy). The most frequently reported adverse reactions were headache, dizziness, and edema in the isradipine group, and cough, headache, and chest pain in the enalapril group. Both drugs produced significant reductions in BP, but, in this study isradipine was more effective. The drugs were similarly well tolerated.

Adult↗

PubMed1991

Systemic vascular effects of cyclosporin A treatment in normotensive rats.

The immunosuppressive drug cyclosporin A (CsA) frequently induces hypertension, but the mechanism(s) is unknown. Thus, we examined the mechanism(s) by which CsA increases arterial blood pressure (MAP) in the normotensive rat. Three different treatment modalities were used. First, chronic CsA treatment (20 mg/kg/day, s.c., for 1 week) significantly increased MAP from 109.6 +/- 2.3 mm Hg to 125.8 +/- 2.9 mm Hg (P less than .05). Second, subacute i.v. infusion of CsA (20 mg/kg daily for 3 days) increased MAP to even higher values (140.5 +/- 2.3 mm Hg), which correlated significantly with the highest circulating values of the drug. The pressor effect after i.v. infusion appears to be unrelated to endogenous release of catecholamines, because phentolamine, which abolishes the response to exogenous norepinephrine, failed to prevent the CsA-induced pressor response. Third, i.v. bolus injections of CsA (10-20 mg/kg) evoked immediate, dose-dependent and short-lasting increases in MAP (+15-25 mm Hg) in both anesthetized and conscious rats. Ganglionic blockade did not prevent this effect, rather, a 2- to 3-fold increase in amplitude (+40-60 mm Hg) and duration (+30-45 min) of the CsA-induced pressor response was observed in anesthetized rats. Heart rate was not increased significantly by either acute or chronic administration of CsA. Our results suggest that both CsA-induced pressor responses and hypertension are due to a peripheral action unrelated to sympathetic outflow. Furthermore, CsA's hypertensive effect is accompanied by severe morphological changes in the vascular endothelium and smooth muscle cells. In addition, CsA-treated rats showed significantly attenuated vasodilatory responses to prostacyclin and sodium nitroprusside, and increased pressor responses to norepinephrine. Thus, a direct vascular action of CsA is likely to contribute to the alterations on systemic vascular responsiveness, as well as to the hypertensive effect of the drug.

Animals↗

PubMed1991

Propranolol promotes cocaine-induced spasm of porcine coronary artery.

Case reports suggest that cocaine use is associated with acute myocardial infarction which may be due to coronary spasm. The present study reports the effect of cocaine on the isolated coronary artery. Ring segments were prepared from the porcine left anterior descending coronary artery and suspended in tissue baths under isometric conditions. Cocaine was ineffective by itself in promoting contraction, but a cumulative concentration-response curve was obtained in the presence of DL-propranolol (1.3 x 10(-6) M); D-propranolol failed to promote cocaine-induced vasoconstriction. The maximum contractile response to cocaine was one-third of the response to histamine and was in the same range as the response to U46619, prostaglandin F2 alpha and norepinephrine. Phenylephrine had a weak effect. In the presence of DL-propranolol, the vasoconstrictive effect of cocaine was subject to rapid tachyphylaxis. Prazosin (5 x 10(-9) M), also in the presence of DL-propranolol, significantly displaced the cocaine concentration-response curve to the right and diminished contractile force by one-half. We conclude that cocaine-induced coronary vasoconstriction elicited in the presence of DL-propranolol can be mediated through local adrenergic mechanisms involving beta receptor antagonism and activation of both alpha-1 and alpha-2 adrenoceptors.

Animals↗

PubMed1990

Pharmacokinetics and effects of recombinant human erythropoietin after intravenous and subcutaneous injections in healthy volunteers.

A double-blind, placebo-controlled study of the pharmacokinetics and safety of multiple doses of recombinant human erythropoietin [rHuEPO 150 or 300 U/kg either by intravenous (IV) bolus or subcutaneously (SC)] in normal male subjects demonstrated that rHuEPO had a dose-related effect on the hematocrit independent of the route of administration and that multiple doses of rHuEPO had no direct pressor effects. When rHuEPO was injected IV, a monoexponential decrease in serum EPO level was evident for 18 to 24 hours postdose. Absorption of SC injected rHuEPO occurred more slowly, with relatively low serum EPO levels being maintained for 48 hours. All rHuEPO antibody titer determinations were negative. With the exception of significant increases in hemoglobin and hematocrit, no clinically significant changes occurred. No hypertensive, convulsive, or thrombotic events were observed. Of the adverse experiences observed in 10 subjects, none was considered clinically significant, and none of the subjects dropped out because of adverse experiences.

Adult↗

PubMed1990

Order-disorder phenomena in myelinated nerve sheaths. II. The structure of myelin in native and swollen rat sciatic nerves and in the course of myelinogenesis.

The algorithm described in the accompanying paper was applied to X-ray scattering experiments performed with rat sciatic nerves, either as a function of the age of the animal (4 to 30 days), or with adult nerves swollen in non-isotonic media. The results were all consistent with the model of disorder used in the theoretical treatment. The algorithm leads, in one step, from the data to the numerical values of the parameters, avoiding all intermediate manipulation. For each experiment a variety of parameters was determined: the average D and the variance sigma 2D of the repeat distance, the average number [N] of motifs per crystallite, the set [idiff(h/D)], which defines the diffuse scattering, the fraction alphaloose of myelin that does not belong to the compact sheaths, and the set [imotif (k/2D)], which suffices to define the continuous intensity curve of the motif imotif(s). Note the remarkable wealth of information, especially by contrast with conventional analyses which, as a rule, only yield the values of D and of the set [imotif(h/D)] (insufficient to determine the function imotif(s]. The function imotif(s) and the parameters D and sigma D (and thus the local structure of the myelin sheaths) were shown to be almost invariant in the course of myelinogenesis; what varies is mainly the total amount of myelin in the nerve and the number of membranes per sheath. Swelling agents have a dramatic influence on the X-ray scattering spectra, but in spite of the conspicuous variation of D, sigma D and [N] the structure of the motif is invariant. The structure of the motif was shown to be quite different in the native and in the swollen samples; the stacking disorder appears to involve mainly the cytoplasmic space in native myelin, the external space in swollen nerves. The very notion of electron density profile, when disorder is present, is discussed. Two criteria were proposed to select the "best" signs of the reflections: two sets came out at almost the same rank, one corresponding to Caspar & Kirschner's the other to Worthington & McIntosh's proposals, neither of which can be ruled out according to the criteria used in this work.

Algorithms↗