Healthy ranges of serum alanine aminotransferase levels in Iranian blood donors

AIM: The healthy ranges for serum alanine aminotransferase (ALT) levels are less well studied. The aim of this study was to define the upper limit of normal (ULN) for serum ALT levels, and to assess factors associated with serum ALT activity in apparently healthy blood donors. METHODS: A total of 1,939 blood donors were included. ALT measurements were performed for all cases using the same laboratory method. Healthy ranges for ALT levels were computed from the population at the lowest risk for liver disease. Univariate and multivariate analyses were performed to evaluate associations between clinical factors and ALT levels. RESULTS: Serum ALT activity was independently associated with body mass index (BMI) and male gender, but not associated with age. Association of ALT with BMI was more prominent in males than in females. Upper limit of normal for non-overweight women (BMI of less than 25) was 34 U/L, and for non-overweight men was 40 U/L. CONCLUSION: Serum ALT is strongly associated with sex and BMI. The normal range of ALT should be defined for male and female separately.     

Healthy ranges of serum alanine aminotransferase levels in Tranian blood donors

AIM:The healthy ranges for serum alanine aminotransferase (ALT) levels are less well studied. The aim of this study was to define the upper limit of normal (ULN) for serum ALT levels, and to assess factors associated with serum ALT activity in apparently healthy blood donors.METHODS: A total of 1 939 blood donors were included.ALT measurements were performed for all cases using the same laboratory method. Healthy ranges for ALT levels were computed from the population at the lowest risk for liver disease. Univariate and multivariate analyses were performed to evaluate associations between clinical factors and ALT levels.RESULTS: Serum ALT activity was independently associated with body mass index (BMI) and male gender, but not associated with age. Association of ALT with BMI was more prominent in males than in females. Upper limit of normal for non-overweight women (BMI of less than 25) was 34 U/L,and for non-overweight men was 40 U/L.CONCLUSION: Serum ALT is strongly associated with sex and BMI. The normal range of ALT should be defined for male and female separately.     

Helicobacter pylori-Associated Upper Gastrointestinal Disease in Saudi Arabia: A Pathologic Evaluation of 298 Endoscopic Biopsies from 201 Consecutive Patients

In a prospective study, histopathological examination 298 upper gastrointestinal (UGI) biopsies, obtained from 201 consecutive patients, was made. Patients were referred with mild to severe dyspeptic symptoms. The aim of the study was to compare the rate of identification of Helicobacter pylori (H. pylori) in the histologically normal gastric mucosa with that in histologically confirmed gastritis or peptic ulcer disease. The gastroduodenal mucosa was histologically normal in 35 patients (17.4%); among those patients, H. pylori was identified in only three (9%). Chronic gastritis was histologically confirmed in 162 patients (80.6%). H. pylori was identified in 123 (76%) of those patients. The difference was statistically significant (p less than 0.00001). Furthermore, when cases with a histological diagnosis of superficial chronic active gastritis (SCAG) are considered separately, the identification rate of H. pylori increases to 88% (121 of 137). When this rate is compared with that of 8% (two of 25), found in superficial chronic quiescent gastritis (SCQG), the difference is highly significant (p less than 0.00001). Of 38 endoscopically diagnosed peptic ulcers, H. pylori was identified in the gastric mucosa of 34 (89%). The organisms were always seen in the antral gastric mucosa, but never in duodenal mucosa. Identification of H. pylori correlates significantly with the histologic activity of chronic gastritis, in both peptic ulcer disease and non-ulcer dyspepsia.     

Photochemotherapeutic Strategy against Acanthamoeba Infections

Acanthamoeba is a protist pathogen that can cause serious human infections, including blinding keratitis and a granulomatous amoebic encephalitis that almost always results in death. The current treatment for these infections includes a mixture of drugs, and even then, a recurrence can occur. Photochemotherapy has shown promise in the treatment of Acanthamoeba infections; however, the selective targeting of pathogenic Acanthamoeba has remained a major concern. The mannose-binding protein is an important adhesin expressed on the surface membranes of pathogenic Acanthamoeba organisms. To specifically target Acanthamoeba, the overall aim of this study was to synthesize a photosensitizing compound (porphyrin) conjugated with mannose and test its efficacy in vitro. The synthesis of mannose-conjugated porphyrin was achieved by mixing benzaldehyde and pyrrole, yielding tetraphenylporphyrin. Tetraphenylporphyrin was then converted into mono-nitrophenylporphyrin by selectively nitrating the para position of the phenyl rings, as confirmed by nuclear magnetic resonance (NMR) spectroscopy. The mono-nitrophenylporphyrin was reduced to mono-aminophenylporphyrin in the presence of tin dichloride and confirmed by a peak at m/z 629. Finally, mono-aminoporphyrin was conjugated with mannose, resulting in the formation of an imine bond. Mannose-conjugated porphyrin was confirmed through spectroscopic analysis and showed that it absorbed light of wavelengths ranging from 425 to 475 nm. To determine the antiacanthamoebic effects of the derived product, amoebae were incubated with mannose-conjugated porphyrin for 1 h and washed 3 times to remove extracellular compound. Next, the amoebae were exposed to light of the appropriate wavelength for 1 h. The results revealed that mannose-conjugated porphyrin produced potent trophicidal effects and blocked excystation. In contrast, Acanthamoeba castellanii incubated with mannose alone and porphyrin alone did not exhibit an antiamoebic effect. Consistently, pretreatment with mannose-conjugated porphyrin reduced the A. castellanii-mediated host cell cytotoxicity from 97% to 4.9%. In contrast, treatment with porphyrin, mannose, or solvent alone had no protective effects on the host cells. These data suggest that mannose-conjugated porphyrin has application for the targeted photodynamic therapy of Acanthamoeba infections and may serve as a model in the development of therapeutic interventions against other eukaryotic infections.     

Synthesis,acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) activities,and molecular docking studies of a novel compound based on combination of flurbiprofen and isoniazide

Synthesis of a compound with balanced bioactivities against a specific target is always a challenging task. In this study, a novel compound (1) has been synthesized by combination of flurbiprofen and isoniazide and shows ∼2.5 times enhanced acetylcholinesterase (AChE) inhibition activity and ∼1.7 times improved butyrylcholinesterase (BuChE) inhibition activity compared to flurbiprofen and a standard drug (i.e. physostigmine). A comparative AutoDock study has been performed, based on the optimized structure, by the DFT/B3LYP method, which confirmed that compound (1) is more active against AChE and BuChE, with calculated binding energies of −12.9 kcal mol⁻¹ and −9.8 kcal mol⁻¹ respectively as compared to flurbiprofen and an eserine (physostigmine) standard for which the binding energy was calculated to be −10.1 kcal mol⁻¹ and −8.9 kcal mol⁻¹, respectively. A mixed mode of inhibition of AChE and BuChE with compound 1 was confirmed by Lineweaver–Burk plots. AChE and BuChE inhibition activity alongside docking results suggests that compound (1) could be used for treatment of Alzheimer''s disease. Moreover, compound (1) also exhibit better α-chymotrypsin activity compared to flurbiprofen. Furthermore, in vitro and in vivo analysis confirmed that compound (1) exhibit more activity and less toxicity than the parent compounds.

A novel compound (1) shows ∼2.5 and ∼1.7 times enhanced AChE inhibition activity and BuChE inhibition activity respectively compared to flurbiprofen and standard drug (i.e. physostigmine). It has also been confirmed by comparative AutoDock studies.     

Discovery of 4-(2-(dimethylamino)ethoxy)benzohydrazide derivatives as prospective microtubule affinity regulating kinase 4 inhibitors

Microtubule affinity regulating kinase 4 (MARK4) is a Ser/Thr kinase, considered as a potential drug target for cancer, diabetes and neurodegenerative diseases. Due to its significant role in the development and progression of cancer, different in-house libraries of synthesized small molecules were screened to identify potential MARK4 inhibitors. A small library of hydrazone compounds showed a considerable binding affinity to MARK4. The selected compounds were further scrutinized using an enzyme inhibition assay and finally two hydrazone derivatives (H4 and H19) were selected that show excellent inhibition (nM range). These compounds have a strong binding affinity for MARK4 and moderate binding with human serum albumin. Anticancer studies were performed on MCF-7 and A549 cells, suggesting H4 and H19 selectively inhibit the growth of cancer cells. The IC₅₀ value of compound H4 and H19 was found to be 27.39 μM and 34.37 μM for MCF-7 cells, while for A549 cells it was 45.24 μM and 61.50 μM, respectively. These compounds inhibited the colonogenic potential of cancer cells and induced apoptosis. Overall findings reflect that hydrazones/hydrazone derivatives could be exploited as potential lead molecules for developing effective anticancer therapies via targeting MARK4.

Inhibition studies of MARK4 with selected hydrazone derivatives.