Exploring physical and chemical properties in new multifunctional indium-, bismuth-, and zinc-based 1D and 2D coordination polymers.

Main group element coordination polymers (MGE-CPs) are important compounds for the development of multifunctional materials. However, there has been a shortage of studies regarding their structural, optical, catalytic, mechanical, and antibacterial properties. This work presents an exhaustive study of a set of crystalline MGE-CPs obtained from bismuth and indium metals and iminodiacetate, 1,2,4,5-benzenetetracarboxylate, and 2,2'-bipyridine as building blocks. An in-depth topological analysis of the networks was carried out. Additionally, nanoindentation studies were performed on two representative low-dimensional compounds in order to find the relationships between their structural features and their intrinsic mechanical properties (hardness and elasticity). The solid-state photoluminescence (SSPL) properties were also studied in terms of excitation, emission, lifetimes values, and CIE chromaticites. Moreover, the heterogeneous catalytic activities of the compounds were evaluated with the cyanosilylation reaction using a set of carbonylic substrates under solvent-free conditions. Finally, the inhibitory effect of the Bi-CPs on the growth of microorganisms such as Escherichia coli, Salmonella enterica serovar Typhimurium, and Pseudomonas aeruginosa, which are associated with relevant infectious diseases, is reported.

Thymosin-alpha 1 plus interferon-alpha for naive patients with chronic hepatitis C: results of a randomized controlled pilot trial.

In this pilot study, we evaluated the efficacy of interferon-alpha (IFN) plus Thymosin-alpha 1 (TA1) to that of IFN alone in naive patients with chronic hepatitis C. Twenty-two patients were randomized to receive interferon-alpha 2b (3 million units three times a week) plus thymosin-alpha l (900 microg/m2 body surface area) and 19 received interferon-alpha 2b alone at the same dose. Patients were treated for 6 months and followed up for another 6 months. Biochemical (alanine aminotransferase values) and virological (hepatitis C virus-RNA) responses to treatment were determined. Combination treatment showed significantly higher efficacy than monotherapy in achieving virological end-of-treatment response (P = 0.03). At 6-month follow up, the sustained biochemical and virological response was not different between the two groups. Our results indicate that the immune modulator TA1 may enhance the end-of-treatment response in naive patients with chronic hepatitis C. Higher doses and/ore more prolonged courses as well as the association with new interferon formulation such as pegylated interferons could improve the sustained response rates to this treatment.

The Rhizobium GstI protein reduces the NH4+ assimilation capacity of Rhizobium leguminosarum.

We show that the protein encoded by the glutamine synthetase translational inhibitor (gstI) gene reduces the NH4+ assimilation capacity of Rhizobium leguminosarum. In this organism, gstI expression is regulated by the ntr system, including the PII protein, as a function of the nitrogen (N) status of the cells. The GstI protein, when expressed from an inducible promoter, inhibits glutamine synthetase II (glnII) expression under all N conditions tested. The induction of gstI affects the growth of a glutamine synthetase I (glnA-) strain and a single amino acid substitution (W48D) results in the complete loss of GstI function. During symbiosis, gstI is expressed in young differentiating symbiosomes (SBs) but not in differentiated N2-fixing SBs. In young SBs, the PII protein modulates the transcription of NtrC-regulated genes such as gstI and glnII. The evidence presented herein strengthens the idea that the endocytosis of bacteria inside the cytoplasm of the host cells is a key step in the regulation of NH4+ metabolism.

Immunization with recombinant Streptococcus gordonii expressing tetanus toxin fragment C confers protection from lethal challenge in mice.

Tetanus toxin fragment C (TTFC) was expressed on the surface of the vaccine vector Streptococcus gordonii, a Gram-positive commensal bacterium of the human oral cavity. The immunogenicity of recombinant S. gordonii expressing TTFC was assayed in mice immunized by the parenteral and mucosal routes. High serum TTFC-specific IgG responses were induced in both BALB/c and C57BL/6 mice immunized subcutaneously. A total of 82% of vaccinated BALB/c mice were protected from the lethal challenge with 50 LD(50) of tetanus toxin (TT) and a direct correlation between the serum TTFC-specific IgG concentration and survival time of unprotected animals was observed. Intranasal immunization of BALB/c mice was also effective in inducing TTFC-specific serum IgG and local IgA in lung washes. Furthermore, 38% of animals immunized intranasally were protected from the lethal challenge with 10 LD(50) of TT while all control animals died within 24 h. Analysis of the serum IgG subclasses showed that the IgG1 subclass was predominant after parenteral immunization in BALB/c mice (IgG1/IgG2a ratio congruent with6) while following mucosal immunization a mixed IgG1 and IgG2a pattern (IgG1/IgG2a ratio congruent with1) was observed. These data show that TTFC expressed on the surface of S. gordonii is immunogenic by the subcutaneous and mucosal routes and the immune response induced is capable of conferring protection from the lethal challenge with TT.

Recombinant Streptococcus gordonii for mucosal delivery of a scFv microbicidal antibody.

The gram-positive bacterium Streptococcus gordonii was engineered to express the microbicidal molecule H6, which is an antiidiotypic single chain antibody mimicking a yeast killer toxin. S. gordonii is a human commensal which we developed as a model system for mucosal delivery of heterologous proteins. The in vivo candidacidal activity of both H6-secreting and H6-surface-displaying streptococcal strains were assayed in a well-established rat model of vaginal candidiasis. At day 21 full clearance of Candida albicans infection was observed in 75% of animals treated with the H6-secreting strain, and in 37.5% of animals treated with the strain expressing H6 on the surface, while all animals treated with the control strain were still infected. The observed candidacidal effect was comparable with that observed with the antimycotic drug fluconazole. These data confirm the potential of H6 as a candidacidal agent and show how promising is the approach of using recombinant bacteria for mucosal delivery of biologically active molecules.

Therapy of mucosal candidiasis by expression of an anti-idiotype in human commensal bacteria.

Two recombinant strains of Streptococcus gordonii, secreting or displaying a microbicidal single-chain antibody (H6), and stably colonizing rat vagina, were used to treat an experimental vaginitis caused by Candida albicans. A post-challenge intravaginal delivery of the H6-secreting strain was as efficacious as fluconazole in rapidly abating the fungal burden. Three weeks after challenge, 75% and 37.5% of the rats treated with the H6-secreting or displaying bacteria, respectively, were cured of the infection, which persisted in 100% of the animals treated with a S. gordonii strain expressing an irrelevant single-chain antibody. Thus, a human commensal bacterium can be suitably engineered to locally release a therapeutic antibody fragment.

Inhibition of glutamine synthetase II expression by the product of the gstI gene.

We report the identification of a previously unrecognized gene that is involved in the regulation of the Rhizobium leguminosarum glnII (glutamine synthetase II) gene. This gene, which is situated immediately upstream of glnII, was identified by means of a deletion/complementation analysis performed in the heterologous background of Klebsiella pneumoniae. It has been designated gstI (glutamine synthetase translational Inhibitor) because, when a complete version of gstI is present, it is possible to detect glnII-specific mRNA, but neither GSII activity nor GSII protein. The gstI gene encodes a small (63 amino acids) protein, which acts in cis or in trans with respect to glnII and is transcribed divergently with respect to glnII from a promoter that was found to be strongly repressed by the nitrogen transcriptional regulator NtrC. A mutated version of GstI lacking the last 14 amino acids completely lost its capacity to repress glnII expression. Our results indicate that gstI mediates the translation inhibition of glnII mRNA and, based on in silico analyses, a mechanism for GstI action is proposed.

On the fate of ingested Bacillus spores.

Spores of various Bacillus species, including B. subtilis, B. cereus and B. clausii, are used as probiotics, although they are generally absent from the normal microflora of man. We used two nonpathogenic Bacillus species, B. subtilis and B. clausii, to follow the fate of spores inoculated intragastrically in mice. We did not find detectable amounts of vegetative cells in intestinal samples, probably because of high toxicity of the conjugated bile salt taurodeoxycholic acid against Bacillus species. Both spores and cells were detected in the lymph nodes and spleen of one mouse. Our results indicate that Bacillus is present in the intestinal tract solely as spores and that nonpathogenic Bacillus spores may germinate in lymphoid organs, a finding reminiscent of B. anthracis germination in macrophages. These results indicate that any claimed probiotic effect of B. subtilis should be due to spores or, alternatively, to vegetative growth outside the intestine.

Behavioral effects of acute and long-term administration of catnip (Nepeta cataria) in mice.

Catnip or catmint (Nepeta cataria) is a plant used extensively to treat human diseases and in toys for pets. We investigated the effects of acute and long-term administration of the plant on some behaviors of mice. The plant was fed as 10% of the normal diet for 2 h/d for 1 or 7 d. Acute and long-term dosing increased both rearing and locomotion frequencies observed in an open field. Acute exposure to catnip increased stereotyped behavior and susceptibility to seizures, did not interfere with haloperidol-induced catalepsy, and decreased sleeping time after sodium pentobarbital administration. Long-term exposure induced tolerance to stereotypic behavior, catalepsy and sleeping time, and increased the susceptibility to seizures induced by picrotoxin and strychnine. An amphetamine-like effect of catnip was suggested to explain the acute effects, while dispositional and functional adaptative changes were considered involved with the long-term effects.

Prostaglandin and thromboxane biosynthesis in resting and activated platelet-free monocytes from aged subjects.

The main cyclo-oxygenase-dependent arachidonic acid (AA) derivatives, i.e. prostaglandin E2 (PGE2) and thromboxane A2 (TXA2), have been measured by radioimmunoassay in platelet-free cultures of human monocytes from young and old subjects, in presence and in absence of activating substances (10% fetal calf serum). No difference was found between cells from the two groups as far as the production of PGE2 and TXB2 (stable metabolite of TXA2) was concerned, at variance with reported data in young and old experimental animals. The addition to the cultures of exogenous AA caused a reorientation of cyclic endoperoxide metabolism resulting in a consistent decrease of the ratio TXB2/PGE2, but only in monocytes from young subjects. The data are discussed with respect to the claimed role of prostaglandins in the age-related immune derangement which is present in aged humans.