Synthesis of benzologues of Nitazoxanide and Tizoxanide: a comparative study of their in vitro broad-spectrum antiprotozoal activity

We have synthesized two new benzologues of Nitazoxanide (NIT) and Tizoxanide (TIZ), using a short synthetic route. Both compounds were tested in vitro against six protozoa (Giardia intestinalis, Trichomonas vaginalis, Entamoeba histolytica, Plasmodium berghei, Leishmania mexicana and Trypanosoma cruzi). Compound 1 (benzologue of NIT) showed broad antiprotozoal effect against all parasites tested, showing IC₅₀’s <5μM. This compound was five-times more active than NIT, and 18-times more potent than metronidazole against G. intestinalis. It was 10-times more active than pentamidine against L. mexicana, and it was sevenfold more potent than benznidazole versus T. cruzi. This compound could be considered as a new broad spectrum antiprotozoal agent.     

The feeding habits of three Mediterranean sea anemone species,Anemonia viridis (Forskål),Actinia equina (Linnaeus) andCereus pedunculatus (Pennant)

The feeding habits of the Mediterranean sea anemonesCereus pedunculatus, Actinia equina andAnemonia viridis were examined mainly by analysing their coelenteron contents. The three species are opportunistic omnivorous suspension feeders. Main source of food forA. viridis andC. pedunculatus are crustaceans (mainly amphipods and decapods, respectively), while for the midlittoral speciesA. equina, it is organic detritus. Using the same method, the temporal and spatial changes in the diet ofA. viridis were examined. During the whole year, crustaceans seem to be the main source of food forA. viridis. The diet composition of this species, however, differs remarkably in space, possibly reflecting the different composition of the macrobenthic organismic assemblages in different areas. The data collected are compared with the limited bibliographical information.     

C-cell in vestiges of the ultimobranchial body in human thyroid glands.

Calcitonin-containing cells were demonstrated in the so-called solid cell nests of three human thyroid glands, which supports the theory of the ultimobranchial origin of these cell nests.     

A Lagrangian Gamma Distribution of the Second Kind

The distribution of the time T for the occurrence of the rth event is derived in a linear function Poisson process, which belongs to a recently introduced family of distributions (JANARDAN and RAO, 1981), called Lagrangian distributions of the second kind (LD₂). In analogy with the ordinary Poisson process, the distribution of the random variable T has been termed the Lagrangian Gamma distribution of the second kind (LG₂); several of its properties and special cases are studied. The frequency function is graphed for some parameter values.     

A novel bufadienolide synthesis

A simple two-step synthesis of bufadienolides is reported. It consists in the addition of the dimethyl acetal of chloroketene to a steroidal 20-methylene 21-aldehyde and in the treatment of the resulting 2,2-dimethoxy 3-chloro 2,3-dihydropyran with sodium methoxide in dimethylsulfoxide. This method is exemplified by the synthesis of 3β-hydroxy-5α,14α-bufadienolide from 3β-acetoxy-20-methylene-5α-pregnan-21-al, prepared from 3β-acetoxy-5α-androstan-17-one. The new procedure represents the most efficient bufadienolide synthesis yet known.     

Thermal Stress Induced Aggregation of Aquaporin 0 (AQP0) and Protection by α-Crystallin via Its Chaperone Function

Aquaporin 0 (AQP0) formerly known as membrane intrinsic protein (MIP), is expressed exclusively in the lens during terminal differentiation of fiber cells. AQP0 plays an important role not only in the regulation of water content but also in cell-to-cell adhesion of the lens fiber cells. We have investigated the thermal stress-induced structural alterations of detergent (octyl glucoside)-solubilized calf lens AQP0. The results show an increase in the amount of AQP0 that aggregated as the temperature increased from 40°C to 65°C. α-Crystallin, molecular chaperone abundantly present in the eye lens, completely prevented the AQP0 aggregation at a 1∶1 (weight/weight) ratio. Since α-crystallin consists of two gene products namely αA- and αB-crystallins, we have tested the recombinant proteins on their ability to prevent thermal-stress induced AQP0 aggregation. In contrast to the general observation made with other target proteins, αA-crystallin exhibited better chaperone-like activity towards AQP0 compared to αB-crystallin. Neither post-translational modifications (glycation) nor C-terminus truncation of AQP0 have any appreciable effect on its thermal aggregation properties. α-Crystallin offers similar protection against thermal aggregation as in the case of the unmodified AQP0, suggesting that αcrystallin may bind to either intracellular loops or other residues of AQP0 that become exposed during thermal stress. Far-UV circular dichroism studies indicated a loss of αhelical structures when AQP0 was subjected to temperatures above 45°C, and the presence of α-crystallin stabilized these secondary structures. We report here, for the first time, that α-crystallin protects AQP0 from thermal aggregation. Since stress-induced structural perturbations of AQP0 may affect the integrity of the lens, presence of the molecular chaperone, α-crystallin (particularly αA-crystallin) in close proximity to the lens membrane is physiologically relevant.     

On-Line Optical and Morphological Studies of Silver Nanoparticles Growth Formed by Nanosecond Laser Irradiation of Silver-Exchanged Silicate Glass

Silver-exchanged silicate glass has been irradiated by 532-nm pulsed Nd:YAG laser in order to locally form metallic nanoparticles. The particular interest of this process is to locally control the silver nanoparticles (NPs) growth. Silver ions are exchanged with sodium ions near the glass surface after dumping of a silicate glass few minutes in silver and sodium nitrates molten salt. A low-energy density laser exposure (0.239 J/cm²) chosen at the ablation threshold allows to observe the kinetics of the silver NPs growth according to the increasing shots number. An on-line optical measurement is carried out after each shot to identify the most important steps during the irradiation process. According to this measurement, we have determined four steps highlighted by UV/Visible spectrophotometry and we have identified the influence of located surface plasmon resonance. Three combined material analysis methods were used to understand the glass/laser interaction mechanism: we outlined the material volume variations by profilometric method, the element distribution by scanning electron microscopy and finally the structural distribution of the irradiated region by a local infrared investigation. The trend for NPs formation revealed by the UV/Visible spectrophotometry is thus explained by the formation of a ring expelled from a central hole. We highlight that the on-line extinction measurement can be used to data process the NPs evolution.     

Quantification of Anti‐Addictive Alkaloids Ibogaine and Voacangine in In Vivo‐ and In Vitro‐Grown Plants of Two Mexican Tabernaemontana Species

Tabernaemontana alba and Tabernaemontana arborea are Apocynaceae species used in Mexican traditional medicine for which little phytochemical information exists. In this study, preliminary gas chromatography/mass spectrometry analyses of different organs obtained from wild plants of both species identified a total of 10 monoterpenoid indole alkaloids (MIAs) and one simple indole alkaloid, nine of which were reported for the first time in these species. Furthermore, callus cultures were established from T. alba leaf explants and regeneration of whole plants was accomplished via somatic embryogenesis. The anti‐addictive MIAs ibogaine and voacangine were then quantified by gas chromatography with flame ionization detection in wild plants of both species, as well as greenhouse‐grown plants, in vitro‐grown plantlets and embryogenic callus of T. alba. Ibogaine and voacangine were present in most samples taken from the whole plants of both species, with stem and root barks showing the highest concentrations. No alkaloids were detected in callus samples. It was concluded that T. alba and T. arborea are potentially viable sources of ibogaine and voacangine, and that these MIAs can be produced through somatic embryogenesis and whole plant regeneration of T. alba. Approaches to increase MIA yields in whole plants and to achieve alkaloid production directly in cell cultures are discussed.