Evaluation of Acetic Acid-Induced Chronic Gastric Ulcer Healing by Propionyl-L-Carnitine Administration

The aim of our study was to investigate the healing effect of propionyl-L-carnitine (PLC) on chronic gastric ulcers and its underlying mechanisms. This study included rats with gastric ulcers induced by applying serosal glacial acetic acid. These rats were then given either saline (vehicle) or PLC at doses of 60 and 120 mg/kg, administered orally 3 days after ulcer induction for 14 consecutive days. Our study found that treatment with PLC resulted in a reduction of the gastric ulcer area, a faster rate of ulcer healing, and stimulated mucosal restoration. Additionally, the treatment with PLC reduced the number of Iba-1+ M1 macrophages while increasing the number of galectin-3+ M2 macrophages, as well as desmin+ microvessels, and α-SMA+ myofibroblasts in the gastric ulcer bed. The mRNA expression of COX-2, eNOS, TGF-β1, VEGFA, and EGF in the ulcerated gastric mucosa was greater in the PLC-treated groups compared with the vehicle-treated rats. In conclusion, these findings suggest that PLC treatment may accelerate gastric ulcer healing by stimulating mucosal reconstruction, macrophage polarization, angiogenesis, and fibroblast proliferation, as well as fibroblast-myofibroblast transition. This process is associated with the upregulation of TGF-β1, VEGFA, and EGF, as well as modulation of the cyclooxygenase/nitric oxide synthase systems.     

Design,in Silico Studies and Biological Evaluation of New Chiral Thiourea and 1,3-Thiazolidine-4,5-dione Derivatives

In this study, new chiral thiourea and 1,3-thiazolidine-4,5-dione derivatives were synthesized, it was aimed to evaluate the various biological activities and molecular docking of these compounds. Firstly, the new thioureas ( 1 – 16 ) were obtained by reacting 1-naphthylisothiocyanate with different chiral amines. Then, the chiral thioureas were cyclized with oxalyl chloride to obtain 1,3-thiazolidine-4,5-dione derivatives ( 17 – 32 ). All compounds were evaluated with several in vitro antioxidant and enzyme inhibition activities. Compound 30 was the most active compound against AChE, with a value of IC₅₀=8.09±0.58 μM. On the other hand, all compounds were tested in silico absorption, distribution, metabolism, and excretion (ADME) assays to better understand their bioavailability. These physicochemical properties, pharmacokinetics, and drug-likeness of all compounds were calculated using SwissADME. Furthermore, according to molecular docking analyses compound 30 exhibited significant binding affinities for all enzymes. Based on our overall observations, compound 30 could be recommended as a potential lead for the therapuetic of Alzheimer's.     

Identification and characterization of ispA, a Shigella flexneri chromosomal gene essential for normal in vivo cell division and intercellular spreading

The virulent phenotype of Shigella requires loci on the chromosome as well as on the large virulence plasmid, and is regulated via a complex web of interactions amongst various chromosomal and large plasmid genes. To further investigate the role of chromosomal loci in virulence, we performed random Tn 10 mutagenesis in Shigella flexneri YSH6000T, and isolated an avirulent mutant (V3404) incapable of spreading throughout an epithelial cell monolayer. Although V3404 initially spread intercellularly at the same rate as the wild-type, it gradually slowed down and ceased spreading as a result of increasing defects in cell division, leading to the formation of long filamentous bacteria lacking septa, trapped within cells. In addition, the mutation affected the ability of V3404 to polymerize actin, a prerequisite for intra- and inter-cellular spreading ability. Sequencing of Tn 10 -flanking DNA revealed that the mutated gene, designated ispA (intracellular septation), was equivalent to a previously sequenced but uncharacterised gene of Escherichia coli located between trp and tonB . Using E. coli sequence data, we cloned the ispA gene from the YSH6000T chromosome and found that it complemented the V3404 mutation. Nucleotide sequencing and in vitro expression experiments revealed that ispA coded for a small (21 kDa), very hydrophobic protein. These results thus show that ispA is an essential virulence gene affecting several functions of the virulence process.     

On the production,elemental composition (C,N, P) and distribution of photosynthetic organic matter in the Southern Black Sea

Chemical oceanographic understanding of the southernBlack Sea has been improved by recent measurements ofthe optical transparency, phytoplankton biomass (interms of chlorophyll-a and particulate organic matter)and primary productivity. During the spring-autmunperiod of 1995–1996, light generally penetrated onlyinto the upper 15–40 m, with an attenuation coefficientvarying between 0.125 and 0.350 m^2122;1. The averagechlorophyll-a (Chl-a) concentrations for the euphoticzone ranged from 0.1 to 1.5 μg l^2122;1. Coherentsub-surface Chl-a maxima were formed near the base ofthe euphotic zone only in summer. Production rate variedbetween 247 and 1925 in the spring and between 405 and687 mgC m^2122;2 d^2122;1 in the summer-autumn period.The average POM concentrations in the euphotic zonevaried regionally and seasonally between 3.8 and28.6 μm for POC, 0.5 and 3.1 μm for PON and0.02 and 0.1 μm for PP. Atomic ratios of C/N, C/Pand N/P, derived from the regressions of POM data,ranged between 7.5 and 9.6, 109 and 165, and 11.2 and16.6, respectively. In the suboxic/anoxic interface,the elemental ratios change substantially due to anaccumulation of PP cohering to Fe and Mn oxides. Thechemocline boundaries and the distinct chemicalfeatures of the oxic/anoxic transition layer (the so-called suboxic zone) are all located at specificdensity surfaces; however, they exhibit remarkablespatial and temporal variations both in their positionand in their magnitude, which permit the definition of long-term changes in the biochemical properties of theBlack Sea upper layer. This revised version was published online in July 2006 with corrections to the Cover Date.     

Elemental diet as primary treatment of acute Crohn's disease: a controlled trial.

Acute exacerbations of Crohn''s disease are usually treated with prednisolone or potentially more toxic immunosuppressive drugs or by surgery. In pilot studies replacing the normal diet by a protein free elemental diet also induced remission. A controlled trial was therefore conducted in which 21 patients acutely ill with exacerbations of Crohn''s disease were randomised to receive either prednisolone 0.75 mg/kg/day or an elemental diet (Vivonex) for four weeks. Assessment at four and 12 weeks showed that the patients treated with the elemental diet had improved as much as and by some criteria more than the steroid treated group. Elemental diet is a safe and effective treatment for acute Crohn''s disease.     

Pindolol acts as beta-adrenoceptor agonist in orthostatic hypotension: therapeutic implications.

Three bedridden patients with severe orthostatic hypotension due to chronic autonomic failure were treated with pindolol (15 mg/day), a beta-adrenoceptor antagonist with partial agonist activity. While taking this drug the patients were free of orthostatic symptoms: they could walk, and standing blood pressure was maintained above 90/50 mm Hg. Supine heart rate rose during treatment by 12-21 beats/minute, and stroke volume and cardiac output by 12-24 ml and 1.5-3.1 l/min respectively. Supine blood pressure rose by 21-68 mm Hg systolic and 14-49 mm Hg diastolic. Pindolol 15 mg/day was therapeutically effective in these three patients with severe orthostatic hypotension due to chronic autonomic failure. Further studies in a larger series of patients are needed to confirm this result.     

Functionally-stabilized proteins--a review

The maintenance or stabilization of protein or enzyme function is of vital importance in Biotechnology. Investigations of thermophilic organisms, studies of denaturation and the use of enzymes in organic solvents have each contributed to an understanding of protein stability. Enzymes can reliably and reproducibly be stabilized by variety of means including immobilization, use of additives, chemical modification in solution and protein engineering. Examples of each of these are discussed. With these recent advances it appears that a rational strategy for achieving a particular stabilized enzyme or protein may be within reach.