Phytochemical constituents,biological activities,and health‐promoting effects of the genus Origanum

Origanum species are mostly distributed around the Mediterranean, Euro‐Siberian, and Iran‐Siberian regions. Since time immemorial, the genus has popularly been used in Southern Europe, as well as on the American continent as a spice now known all over the world under the name “oregano” or “pizza‐spice.” Origanum plants are also employed to prepare bitter tinctures, wines, vermouths, beer, and kvass. The major components of Origanum essential oil are various terpenes, phenols, phenolic acids, and flavonoids with predominant occurrence of carvacrol and thymol (with reasonable amounts of p‐cymen and ‐terpinene) or of terpinene‐4‐ol, linalool, and sabinene hydrate. Many species of Origanum genus are used to treat kidney, digestive, nervous, and respiratory disorders, spasms, sore throat, diabetes, lean menstruation, hypertension, cold, insomnia, toothache, headache, epilepsy, urinary tract infections, etc. Origanum essential oil showed potent bioactivities owing to its major constituents' carvacrol, thymol, and monoterpenes. Several preclinical studies evidenced its pharmacological potential as antiproliferative or anticancer, antidiabetic, antihyperlipidemic, anti‐obesity, renoprotective, antiinflammatory, vasoprotective, cardioprotective, antinociceptive, insecticidal, and hepatoprotective properties. Its nanotechnological applications as a promising pharmaceutical in order to enhance the solubility, physicochemical stability, and the accumulation rate of its essential oils have been investigated. However, Origanum has been reported causing angioedema, perioral dermatitis, allergic reaction, inhibition of platelet aggregation, hypoglycemia, and abortion. Conclusive evidences are still required for its clinical applications against human medical conditions. Toxicity analyses and risk assessment will aid to its safe and efficacious application. In addition, elaborate structure–activity studies are needed to explore the potential use of Origanum‐derived phytochemicals as promising drug candidates.     

Seroprevalance of pertussis antibodies in maternal and cord blood of preterm and term infants

Background

The resurgence of pertussis has resulted in an increased morbidity and mortality, especially among young infants. The aim of our study was to determine the antibody concentrations against pertussis antigens in cord and maternal blood in both preterm and term infant–mother pairs and to evaluate the efficacy of transplacental antibody transfer.

Methods

Antibodies to pertussis toxin (PT) and filamentous hemagglutinin (FHA) in maternal and cord blood samples were measured by in-house enzyme linked immunosorbent assay (ELISA) in 100 preterm infant–mother and 100 term infant–mother pairs. Geometric mean concentrations (GMCs) of pertussis antibodies and cord:maternal GMC ratios were calculated.

Results

Cord GMCs for anti-PT and anti-FHA in the preterm group were 13.15 and 14.55 ELISA U/ml (EU/ml), respectively. Cord GMCs for anti-PT and anti-FHA in the term group were 19.46 and 19.18 EU/ml, respectively. Cord anti-PT GMC was significanlty lower in the preterm group (p = 0.037). There were no differences between the groups with regard to maternal anti-PT and anti-FHA GMC. Placental transfer ratios for anti-PT and anti-FHA in preterms were 68% and 72%, respectively. The same ratios in terms were 107% and 120%, respectively and were significantly higher than those of preterms (p < 0.001). Placental transfer ratios were even lower in preterms <32 weeks when compared to preterms ≥32 weeks and terms. There was a strong correlation between maternal and cord anti-pertussis antibody levels both in preterm and term infants.

Conclusions

Anti-pertussis antibody levels were generally low in infant–mother pairs and would not be adequate to confer protection until the onset of primary immunization series. Transplacental anti-pertussis antibody transfers and antibody levels were lower in the cord blood of preterm infants, especially in those <32 weeks. These findings support the rationale for maternal immunization, which in combination with cocooning, could be a better option for preterm infants.     

Synthesis and evaluation of novel xanthene-based thiazoles as potential antidiabetic agents

A series of xanthene-based thiazoles was synthesized and characterized by different scpectroscopic methods, i.e. Proton nuclear magnetic resonance (¹H NMR), carbon nuclear magnetic resonance (¹³C NMR), infrared spectroscopy, carbon hydrogen nitrogen analysis, and X-ray crystallography. The inhibition potencies of 18 newly synthesized thiazole derivatives were investigated on the activities of acetylcholinesterase (AChE), butyrylcholinesterase (BChE), α-amylase (α-Amy), and α-glycosidase (α-Gly) enzymes in accordance with their antidiabetic and anticholinesterase ability. The synthesized compounds have the highest inhibition potential against the enzymes at low nanomolar concentrations. Among the 18 newly synthesized molecules, 3b and 3p were superior to the known commercial inhibitors of the enzymes and have a much more effective inhibitory potential, with IC₅₀: 2.37 and 1.07 nM for AChE, 0.98 and 0.59 nM for BChE, 56.47 and 61.34 nM for α-Gly, and 152.48 and 124.84 nM for α-Amy, respectively. Finally, the optimized 18 compounds were subjected to molecular docking to describe the interaction between thiazole derivatives and AChE, BChE, α-Amy, and α-Gly enzymes in which important interactions were monitored with amino acid residues of each target enzyme.     

Synthesis and characterization of flurbiprofen hydrazide derivatives as potential anti-HCV, anticancer and antimicrobial agents

A novel series of new flurbiprofen hydrazide derivatives 2-(2-fluorobiphenyl-4-yl)-N′-[(substituted phenyl/5-nitro-2-furyl)methylene]propanehydrazide (3a–k), 2-(2-fluorobiphenyl-4-yl)-N-(2-substituted-4-oxo-1,3-thiazolidine-3-yl)propanamide (4a–b, 4d–k), 2-[2-(2-fluorobiphenyl-4-yl) propanoyl]-N-substituted hydrazinecarbothioamide (5a–h) and 2-(2-fluorobiphenyl-4-yl)-N′-[(3-methyl-4-oxo-1,3-thiazolidin-2-ylidene]propanehydrazide (6a–b, 6e and 6g) has been synthesized in this study. All synthesized compounds were screened for antimicrobial activity against various bacterial and fungal strains. Additionally, compounds were evaluated for the ability to inhibit Hepatitis C virus NS5B polymerase. The most active 4-thiazolidinone compound was 4k (SGK119) with 67.0 % and thiosemicarbazide compound was 5d (SGK123) with 69.50 % inhibition at 200 μM against hepatitis C virus NS5B RNA polymerase. Anticancer activity of the selected compounds (3i, 3j, 3h, 4d, 4i and 6b) was determined at a single dose towards the full panel of 60 human cancer cell lines by the National Cancer Institute (NCI). 2-(2-Fluoro-4-biphenylyl)-N-[2-[4-(trifluoromethyl)phenyl]-4-oxo-1,3-thiazolidine-3-yl]propanamide 4d, containing thiazolidinone ring, demonstrated the most marked effect with 20.80 % growth percent on leukaemia cancer cell line SR at 10^?5 M. The results demonstrated that none of the compounds tested have anticandidal and antifungal activities, but two of them (4a and 4i) showed antibacterial inhibition against Micrococcus luteus, and Staphylococcus cohnii and Staphylococcus aureus, respectively.     

Association Between Thr21Met and Ser89Asn Polymorphisms of the Urotensin-II (UTS2) Gene, Diabetes Mellitus, and Diabetic Retinopathy

Purpose: To evaluate possible role of the UTS2 gene polymorphisms (Thr21Met and Ser89Asn) in the genetic susceptibility to diabetic retinopathy (DR) in a Turkish population. Methods: Total number of 280 patients with DR (nonproliferative DR 170 and proliferative DR 110), 291 nondiabetic healthy controls, and 113 diabetic controls (without DR) were included to this study. The detection of UTS2 gene polymorphisms was achieved with PCR-RFLP technique. The Discovery Studio 2.1 program was used for molecular modeling analysis. Results: Thr21Met (T21M) and Ser89Asn (S89N) polymorphisms of the UTS2 gene were associated with the risk of developing diabetes and DR. M21M genotype frequencies were high in PDR (8.9% in diabetic control vs. 54.6% in PDR, P = 0.0092) group. Increases in 21M allele frequency (52.7% in diabetic control vs. 76.4% in PDR, P < 0.0001) frequency in PDR group were detected. However, there were no changes in genotype and allele frequencies for T21M in NPDR group. There were decreases in the S89N genotype (23.9% in diabetic control vs. 13.5%) and 89N allele frequencies (11.9% in diabetic control vs. 6.8%) in NPDR group. However, S89S genotype (76.1% in diabetic control vs. 86.4%) and 89S allele frequencies (88.1% in diabetic control vs. 93.2%) were high in NPDR group. Three haplotypes (MN, MS and TS) were associated with NPDR patients (P < 0.001), but only MN (P < 0.001) and TS haplotypes (P = 0.018) were associated in PDR group. Molecular modeling analysis showed that these two polymorphisms changed the 3D structure of UTS2, and provided interactions with neighboring residues. Conclusion: The associations between Thr21Met and Ser89Asn polymorphisms in the UTS2 gene and DR strongly suggest that these SNPs may be an important a risk factor for the development of DR in Caucasians, and could be candidate markers for earlier diagnosis and targets for DR therapy.     

The effects of reactive oxygen species on calcium- and carbachol- induced contractile responses in β-escin permeabilized rat bladder

The effect of reactive oxygen species on contractions in beta-escin permeabilized rat detrusor was investigated. Cumulative calcium contractions were inhibited by hydrogen peroxide (H(2)O(2)) and hydroxyl (*OH) but not by superoxide (O(2) *). The sarcoplasmic reticulum calcium-ATPase inhibitor cyclopiazonic acid (CPA) and the mitochondrial blocker carbonyl cyanide p-trifluromethoxyphenylhydrazone (FCCP) decreased the calcium contractions, however in their presence, H(2)O(2) and *OH did not have further effect. Carbachol contractions were inhibited by either H(2)O(2)/*OH/O(2) * or CPA/FCCP. In the presence of CPA, carbachol contractions were not affected by H(2)O(2) and *OH but further decreased by O(2) *. On the other hand, only H(2)O(2) and *OH elicited additional inhibition in carbachol responses in the presence of FCCP. Inositol triphosphate contraction was inhibited by *OH whereas none of the radicals affect carbachol induced calcium sensitization. These results show that H(2)O(2) and *OH affects sarcoplasmic reticulum where O(2) * acts on mitochondria to change contractions in rat detrusor smooth muscle.     

Intravenous theophylline decreases post-dural puncture headaches

Post-dural puncture headache (PDPH) is a common complication of lumbar puncture. As invasive treatments for PDPH have known complications, pharmacologic management may be preferable. The aim of this study was to evaluate and to compare the efficacy of intravenous theophylline treatment for PDPH, in comparison with a placebo. We found that intravenous theophylline infusion was effective for decreasing the painfulness of PDPH compared with the control group. The mean visual analogue scale (VAS) value was 7.05+/-1.47 before the theophylline infusion and 2.88+/-2.31 after infusion. An average of 59.1% relief of pain was obtained in the group treated with theophylline infusion. The improvement in VAS in the study group was significant (p<0.001), whereas that in the control group was not (p=0.15). The mean VAS decrease after theophylline infusion was 4.17+/-2.03 in the study group and 0.41+/-0.71 in the control group; the difference in improvement between the groups was significant (p<0.001). Intravenous theophylline infusion is an easy, rapid, minimally invasive, an effective treatment for PDPH. It may be attempted in PDPH patients before invasive techniques are used. To the best of our knowledge, this is the first report on the effect of intravenous infusion of theophylline compared with a placebo in the treatment of PDPH.     

Rare gallbladder parasitosis mimicking cholelithiasis: Dicrocoelium dendriticum

Cholelithiasis is increasingly diagnosed in childhood and infancy. Biliary parasites are the rarest cause of cholelithiasis in all age groups. We present a twelve-year-old girl with non-hemolytic gallbladder stone and discuss the clinical features and differential diagnosis of Dicrocoelium dendriticum (DD) invasion that causes and/or mimics cholelithiasis in children.     

Use of extracorporeal circulation and selective renal perfusion during the surgical correction of abdominal aortic coarctation

Coarctation of the abdominal aorta is a rare pathology. Stenosis of visceral and renal arteries may present together with coarctation, which requires specific operation techniques. We present the case of a patient with coarctation of the abdominal aorta associated with stenosis of the celiac trunk, the superior mesenteric and the right renal arteries. Distal aortic perfusion by extracorporeal circulation and selective right renal perfusion techniques were used during the operation to protect the spinal cord and kidney against hypoperfusion and ischemia.