Effect of water extract of Turkish propolis on tuberculosis infection in guinea-pigs.

Mycobacterium tuberculosis (H(37)R(v))-infected guinea-pig model was used to investigate the effect of water extract of propolis (WEP). After subcutaneous inoculation of tubercle bacilli, each animal received oral WEP (n=9), isoniazid (n=5) or saline (n=6) as placebo and were sacrificed 30 days later. Formation of necrosis was less prominent in the group treated with WEP, but was not statistically significant (P>0.05). The granuloma formation in the same group was more prominent than the placebo and isoniazid groups; however, this finding failed to reach statistical significance by the Kruskal-Wallis test (P>0.05). These findings suggest that Turkish WEP may have a limited effect on the development of tuberculosis infection in this guinea-pig model.     

Immunological evaluation of personalized peptide vaccination in refractory small cell lung cancer

Since the prognosis of small cell lung cancer (SCLC) remains poor, development of new therapeutic approaches, including immunotherapies, would be desirable. In the current study, to evaluate immunological responses in refractory SCLC patients, we conducted a small scale phase II clinical trial of personalized peptide vaccination (PPV), in which vaccine antigens are selected based on pre-existing host immunity. Ten refractory SCLC patients, who had failed to respond to chemo- and/or chemoradiotherapies (median number of regimens, 2.5; median duration, 20.5 months), were enrolled. A maximum of four human leukocyte antigen (HLA)-matched peptides showing higher antigen-specific humoral responses were subcutaneously administered (weekly for six consecutive weeks and then bi-weekly thereafter). PPV was terminated before the 3rd administration in four patients because of rapid disease progression, whereas the remaining six patients completed at least one cycle (six times) of vaccinations. Peptide-specific immunological boosting was observed in all of the six patients at the end of the first cycle of vaccinations, with their survival time of 25, 24.5 (alive), 10 (alive), 9.5, 6.5, and 6 months. Number of previous chemotherapy regimens and frequency of CD3(+) CD26(+) cells in peripheral blood were potentially prognostic in the vaccinated patients (hazard ratio [HR] = 2.540, 95% confidence interval [CI] = 1.188-5.431, P = 0.016; HR = 0.941, 95% CI = 0.878-1.008, P = 0.084; respectively). Based on the feasible immune responses in refractory SCLC patients who received at least one cycle (six times) of vaccinations, PPV could be recommended for a next stage of larger-scale, prospective clinical trials.     

Synergistic effects of topoisomerase I inhibitor, 7-ethyl-10-hydroxycamptothecin, and irradiation in a cisplatin-resistant human small cell lung cancer cell line.

7-ethyl-10-[4-(1-piperidyl)-1-piperidyl] carbonyloxy-camptothecin, a topoisomerase I (topo I) inhibitor, is one of the most active agent against lung cancer, and its radiosensitizing effect has been reported recently. We evaluated a combination in vitro effect of irradiation and 7-ethyl-10-hydroxy-CPT (SN-38), an active metabolite of 7-ethyl-10-[4- (1-piperidyl)-1-piperidyl] carbonyloxy-camptothecin, on a human small cell lung cancer cell line (SBC-3) and its cisplatin-resistant subline (SBC-3/CDDP). Growth-inhibitory effects of irradiation with or without SN-38 were determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. A modified isobologram method was used to evaluate the treatment interaction. The combination of irradiation and SN-38 showed a synergistic inhibitory effect on the growth of SBC-3/CDDP despite its cross-resistance to irradiation and SN-38. In contrast, the same combination showed only an additive effect on the growth of parental SBC-3 cells. There was no significant difference in topo I protein expression between these two cell lines. In SBC-3 cells, topo I catalytic activity was suppressed by 4 Gy of irradiation, without a decrease of nuclear topo I protein, whereas the exposure of SBC-3 cells to 1 microM SN-38 subsequent to irradiation showed no remarkable additional effects on both topo I activity and protein content. On the other hand, in SBC-3/CDDP cells, topo I activity was unchanged by irradiation, but the subsequent exposure to SN-38 gave rise to a decrease in topo I activity, which was accompanied by a significant decrease in the topo I protein content (P = 0.02). These observations may indicate that SN-38 induces sequestration of topo I onto DNA in radiation-treated SBC-3/CDDP cells and suggest that the synergistic effect of irradiation and SN-38 in SBC-3/CDDP cells was considered attributable to DNA repair-related enhanced recruitment of topo I onto the damaged DNA.     

Probiotics in Experimental Ulcerative Colitis: Mast Cell Density and Neuronal Hypertrophy

Background:Probiotics such as Lactobacillus and Bifidobacterium are among the supportive treatment methods to achieve effective results in ulcerative colitis. This study was established to investigate the effect of probiotics in experimental ulcerative colitis and to detect changes in mast cell and neuronal structures in this treatment method.Methods:A total of 48 adult male rats were used to study the effects of probiotics on ulcerative colitis. The animals were divided into 6 groups as control, experimental colitis, and four probiotic protective groups. Three different bacterial strains were administered to the protective groups individually and in combination by gavage. PGP 9.5 antibody and mast cell tryptase were used for the detection of neuronal structures and mast cells. The number of Schwann cells and ganglia, size measurements of ganglia, and density of mast cells were evaluated.Results:Compared to the control, an increase in the number of mast cells was detected in all groups. Especially the increase in the number of mast cells was found to be statistically significant in combined probiotic administration. In the detection of neuronal structures, a significant increase in the number of Schwann cells and ganglia was detected in groups where probiotics were administered combined and individually.Conclusion:These results suggest that probiotics may play a role in the supporting effect of increasing the number of mast cells and neuronal structures, protecting the intestinal wall. We think that more specific and detailed studies should be conducted to evaluate the protective/therapeutic effect of probiotics in future studies.     

Evidence for direct effect of tolbutamide on hepatic glycogenolysis induced by Ca2+-dependent hormones

The effects of tolbutamide and glibenclamide on hepatic glycogenolysis in perfused rat liver were investigated. Tolbutamide per se did not influence glucose output from the liver, but at therapeutic concentrations (about 350 microM) it significantly inhibited the glycogenolysis induced by phenylephrine, vasopressin and angiotensin II, while glibenclamide did not. Neither tolbutamide nor glibenclamide inhibited the glycogenolysis induced by glucagon. Tolbutamide potentiated the inhibitory effect of submaximal concentrations of insulin on glycogenolysis induced by phenylephrine. This effect of tolbutamide was elicitable even in the absence of calcium in the perfusate, and was additive to that of trifluoperazine. However, tolbutamide did not potentiate the inhibitory effect of insulin on glucagon-induced glycogenolysis. Tolbutamide inhibited the glycogenolysis induced by A23187, a calcium ionophore. These results indicate that, in addition to its known effect on insulin secretion, tolbutamide has a direct effect on the liver to inhibit glycogenolysis induced by Ca2+-dependent hormones (catecholamines, vasopressin and angiotensin II) and A23187. Thus, it is likely that tolbutamide inhibits the effect of Ca2+ mobilized by Ca2+-dependent hormones to stimulate glycogenolysis.     

A large negative magnetoresistance effect in semiconducting crystals composed of an octahedrally ligated phthalocyanine complex with high-spin manganese(iii)

A design for an octahedrally ligated phthalocyanine complex with high-spin manganese(iii) (S = 2) and Mn^III(Pc)Cl₂ (Pc = phthalocyanine) is presented. The presence of high-spin state Mn^III in the fabricated Ph₄P[Mn^III(Pc)Cl₂]₂ (Ph₄P = tetraphenylphosphonium) semiconducting molecular crystal is indicated by the Mn–Cl distance, which suggests an electronic configuration of (d_yz, d_zx)²(d_xy)¹(d_z²)¹. This was confirmed by the Curie constant (C = 5.69 emu K mol⁻¹), which was found to be significantly larger than that of the isostructural Ph₄P[Mn^III(Pc)(CN)₂]₂, where Mn^III adopts a low-spin state (S = 1). The magnetoresistance (MR) effects of Ph₄P[Mn^III(Pc)Cl₂]₂ at 26.5 K under 9 T static magnetic fields perpendicular and parallel to the c-axis were determined to be −30% and −20%, respectively, which are significantly larger values than those of Ph₄P[Mn^III(Pc)(CN)₂]₂. Furthermore, the negative MR effect is comparable to that of Ph₄P[Fe^III(Pc)(CN)₂]₂ (S = 1/2), which exhibits the largest negative MR effect reported for [M^III(Mc)L₂]-based systems (Mc = macrocyclic ligand, L = axial ligand). This suggests that the spin state of the metal ion is the key to tuning the MR effect.

A Ph4P[Mn^III(Pc)Cl2]2 molecular crystal where Mn^III adopts a high-spin state (S = 2) was designed. The large magnetoresistance effect of fabricated Ph4P[Mn^III(Pc)Cl2]2 suggests that the spin state of the metal ion is the key to tuning the MR effect.     

The involvement of neuropeptide Y in the antimuricide action of noradrenaline injected into the medial amygdala of olfactory bulbectomized rats

The present study was designed to clarify the functional role of neuropeptide Y (NPY) in the regulation of muricide induced by olfactory bulbectomy (OB) in relation to that of noradrenaline (NA) in the medial amygdala (AME). NA injected into AME inhibited muricide dose-dependently in OB rats. NPY at doses of 5 and 10 micrograms/microliter injected alone into AME failed to suppress muricide. When NPY 10 micrograms was injected into AME in combination with the maximal non-effective dose of NA, which was determined in each rat, muricide was suppressed in 80% of OB rats. The present study has provided the first evidence suggesting that NPY may be involved in the regulation of OB-induced muricide.     

Genetically Diverse Highly Pathogenic Avian Influenza A(H5N1/H5N8) Viruses among Wild Waterfowl and Domestic Poultry,Japan, 2021

Genetic analyses of highly pathogenic avian influenza H5 subtype viruses isolated from the Izumi Plain, Japan, revealed cocirculation of 2 genetic groups of clade 2.3.4.4b viruses among migratory waterfowl. Our findings demonstrate that both continuous surveillance and timely information sharing of avian influenza viruses are valuable for rapid risk assessment.     

Population-level interest in anti-rheumatic drugs in the COVID-19 era: insights from Google Trends

Clinical Rheumatology - The general public may utilize online information through search engines for implications and risks of some anti-rheumatic drugs. These drugs have been used in the...