Reaction of some antiinflammatory 17 beta-(2-aminooxazol-4-yl) steroids with hydrogen peroxide. Synthesis of steroid-17-spiro-5'-oxazolidine-2',4'-diones

The heterocyclic moiety of 17 beta-(2-aminooxazol-4-yl) steroids is sensitive to the oxidizing action of hydrogen peroxide and yields products mainly from the opening of the amino-oxazole ring. Unlike simple 2-aminooxazoles, it does not rearrange to 2-imidazolone and the expected steroidal hydroperoxyimidazolidinones were not detected. Among the substances we isolated, N-(aminocarbonyl)-17 alpha-hydroxy-17-carboxamides (2a) and (3a) undergo spontaneous cyclization, in the reaction conditions, giving steroid-17-spirooxazolidinediones (2d) and (3d). Spirane (2d) was synthesized in high yields from (2a) in strongly alkaline medium.     

Calorimetric studies of oxyhemoglobin dissociation. II. Erythrocytic oxygen depletion by sodium dithionite

Dithionite causes the depletion of dioxygen from suspensions of erythrocytes by reduction of the external dioxygen and not by diffusion into the cell. The molar enthalpy for the reduction shows a small difference with respect to the values found for free hemoglobin; and the normal stoichiometry of 2 moles dithionite/mole dioxygen found there is not observed with erythrocytes. At low hematocrit, the stoichiometry is 2.6:1 and decreases to 1.5:1 at high hematocrit. The change is not due to differences in the hemoglobin saturation or to an inability of dithionite to reduce all dioxygen present at the higher hematocrit. Neither catalase nor peroxidase added to the extracellular volume significantly alters the stoichiometry or the enthalpy of dioxygen reduction by dithionite. Addition of superoxide dismutase, however, restores the normal stoichiometry at high hematocrit and further increases the stoichiometry at low hematocrit. The calorimetrical signal of hydrogen peroxide, clearly seen with free dioxygen, is not present with erythrocytes. In all these cases the total heat evolved is the same.     

Modulation of endogenous prostaglandins by thymosin-α1 in lymphocytes

The effects of thymosin-α₁ on the stimulation of specific release of prostaglandin E₂ (PGE₂) from splenic lymphocytes and thymocytes were studied. Experiments were also performed to study in parallel the absolute levels of thymosin-α₁ in the blood and the induction of serum FTS activity and of azathioprine sensitivity of spleen cells from adult thymectomized (ATx) mice. A significant difference in the release of PGE₂ between normal splenocytes and splenocytes from ATx mice was observed. Thymosin-α₁ at certain concentrations was able to stimulate PGE₂ release from lymphocytes of ATx mice while inhibiting release in lymphocytes of normal mice. Also, thymocytes were stimulated to release PGE₂ after incubation with α₁ in a manner similar to that seen in spleen cells of ATx mice. Approximately the same concentration of α₁ was found to also correct the low azathioprine sensitivity of splenocytes from ATx mice. Determinations of FTS-like activity in the blood and the pharmacokinetics of α₁ after administration of this synthetic molecule show a clear dissociation. A maximum peak of α₁ activity was obtained after 1 hr, while maximal FTS-like activity was observed after 24 hr. The inhibition of the induction by α₁ of FTS-like activity and of Thy 1.2 antigen by indomethacin suggests that the action of α₁ requires prostaglandin biosynthesis.     

Intercellular communication in rat seminiferous tubules

Intercellular electrical coupling in seminiferous tubules from prepubescent and adult Wistar rats has been studied by using conventional techniques. It is found that cells in the seminiferous epithelium are electrically coupled. Experiments performed using "Sertoli cell-enriched" seminiferous tubules indicate the existence of intercellular ionic communication between Sertoli cells. Junctional conductance is independent of the direction of electrical field and it is affected by A23187 Ca ionophore (5 microM) but not by exposure to the neurotransmitter norepinephrine (1-5 X 10(-5) M). Intracellular resistivity (including junctional resistance) is higher in mature as compared to immature germinal epithelium. These findings suggest that cell metabolites or second messenger molecules could be transferred via the low-resistance pathways between epithelium cells to coordinate cellular activity.     

Distribution and abundance of house-dust mites (Acarina: Pyroglycphidae) in Rome,Italy

For the first time in Rome, house-dust mite infestation was studied in 90 randomly selected houses. In each house, mite infestation was assessed in three sites: mattress, bedroom and living room. In total, 87.8% of the sampled houses were positive for dust mites. In the houses infested, 11.4% showed densities of >100 mites/g of dust, 15.2% registered densities between 50 and 99, and in the remaining houses (73.4%), the densities were between 1 and 49 mites/g dust. The percentages of infested houses were positively correlated with the relative humidity (RH) values (r=0.89,P=0.02). At the lowest range of RH (between 46 and 50), the infestation was 50% and at the highest range of RH (between 73 and 78) it was 100%. The mattress was significantly the most infested (71.1%) of the tested sites. Only wool and spring mattresses were infested, and they did not show any significant differences in mite concentrations.Dermatophagoides farinae was the most abundant species (53.1%), followed byGlycyphagus domesticus (34.5%),D. pteronyssinus (5.2%), andEuroglyphus maynei (0.2%);D. farinae was also the most frequent species (56.9%). The remaining specimens (7.0%) were predator species commonly found in houses. The prevalence ofD. farinae in Rome is discussed.     

Two forms of phosphoinositol kinase from germinating mung bean seeds

Phosphoinositol kinase, the key enzyme responsible for the biosynthesis of higher inositol phosphates has been isolated from the cotyledons of mung beans germinated for 24 hr and has been resolved into two different forms, phosphoinositol kinase A and phosphoinositol kinase B. Both forms were purified to homogeneity and characterized. The K_m values for ATP with phosphoinositol kinase A (1.78 × 10^?4 M) and phosphoinositol kinase B (3.12 × 10 ^?5 M) showed that phosphoinositol kinase B had a greater affinity for ATP. ATP could be partially replaced as phosphate donor by UTP and phosphoenolpyruvate in the case of phosphoinositol kinase A but not in the case of phosphoinositol kinase B.     

Studio comparativo sulla flora urbana in Italia

Abstract

Lo studio è basato sul confronto tra la flora di 5 città localizzate nelle principali regioni fitoclimatiche italiane: Milano, Ancona, Roma, Cagliari e Palermo. L'analisi di 684 specie rilevate in 50 aree campione ha evidenziato l'importanza delle apofite nella flora urbana in Italia e il ruolo delle terofite che provengono direttamente dalla vegetazione mediterranea. Il confronto ha inoltre mostrato la dominanza dei fattori biogeografici nella costituzione della copertura vegetale delle 5 città. Questi risultati contrastano con l'elevata percentuale di specie esotiche e con l'uniformità floristica osservate nelle aree urbane dell'Europa Centrale.     

Mitochondrials complex I activity is reduced in latent adriamycin-induced cardiomyopathy of rat

We previously reported on the use of enzymatic analysis to impair fatty acid metabolism followed by reduced myocardial energy content, leading to severe heart failure in adriamycin (ADR)-treated rats. The aim of this study is to investigate whether impaired myocardial energy metabolism can also be detected by other methods; i.e. measuring mitochondrial complex I activity and myocardial ¹²⁵I-15-(p-iodophenyl)-3-(R,S)- methylpentadecanoic acid (BMIPP) accumulation in ADR-treated rats. Eight-week-old male Sprague-Dawley rats received 6 intraperitoneal injections of ADR (total 15 mg/kg: group ADR) or saline (control group) over 2 weeks. Left ventricular (LV) ejection fraction was assessed using echocardiography at 3- and 6-weeks after ADR injection (3 weeks and 6 weeks, respectively). Myocardial fatty acid utilization was assessed at 3 weeks and 6 weeks. The myocardial counts of BMIPP were measured after intravenous BMIPP (370 kBq) injection, and ¹²⁵I counts were measured to calculate the uptake ratio. The enzymatic activity of complex I was assessed by monitoring the oxidation of nicotinamide-adenine-dinucleotide-disodium-salt (NADH). In rats treated with ADR, significant decrease in LV ejection fraction was observed only at 6 weeks compared to control (72.5 vs. 84.5%, p < 0.01rpar;. LV ejection fraction at 3 weeks was identical between group ADR and control (81.8 vs. 84.4%). However, at 3 weeks, complex I activity was already reduced significantly in group ADR as compared to control group (p = 0.03), but the reduction in BMIPP accumulation was not (p = 0.15). Our data indicated that reduced complex I activity in a phenomenon occurred in early phase of ADR-induced cardiomyopathy, and it might play an important role in the progression of ADR-induced heart failure.     

Antiplasmodial activity of (I-3,II-3)-biflavonoids and other constituents from Ormocarpum kirkii

Preliminary screening of a series of medicinal plants, traditionally used in Tanzania, showed an IC₅₀ of 15.6-31.2 μg/ml for the crude extract of the root of Ormocarpum kirkii S. Moore (Papilionaceae) against Plasmodium falciparum. A bioguided isolation was performed in order to isolate the active constituents. Twelve constituents were obtained and identified using NMR and MS data, and optical rotation measurements. The compounds comprised seven (I-3,II-3)-biflavonoids, three (I-3,II-3)-bi-4-phenyldihydrocoumarins, an isoflavanone and a C-glucosylated flavone. Six compounds, liquiritigeninyl-(I-3,II-3)-naringenin, apigeninyl-(I-3,II-3)-naringenin, 7-O-β-D-glucopyranosylchamaejasmin, (3R,4S,3″R,4″S)-5,5″-di-O-methyldiphysin, 7-O-β-D-glucopyranosyldiphysin, and 4″-hydroxydiphysolone, were isolated in addition to six known components. The compounds were evaluated for antimicrobial activity in a broad screening panel, including P. falciparum. Seven of these showed antiplasmodial activity; isochamaejasmin being the most active with an IC₅₀ of 7.3 ± 3.8 μM, but the selectivity was rather limited. Thus, these constituents may contribute, at least in part, to the antimalarial use of O. kirkii in traditional medicine.