The effects of smoking on neutrophil/lymphocyte, platelet/ /lymphocyte ratios.

OBJECTIVE: The aim of this study was to compare the Neutrophil to Lymphocyte ratio (NLR), Platelet to Lymphocyte ratio (PLR) and Mean Platelet Volume to Platelet (MPV/Plt) ratio of smokers and non-smokers. METHODS: Two hundred smokers and two hundred non-smoking healthy volunteers were enrolled in this study. Sociodemographic data and hematologic parameters of all patients were recorded. NLR, PLR and MPV/Plt ratios were calculated. RESULTS: The mean age of the case group was 35.88 ± 10.56 and the mean age of the control group was 38.97 ± 10.56. 80 % (n = 160) of the smokers were male and 20 % (n = 40) were female. 27.5 % (n = 55) of the control group were male and 72.5 % (n = 145) were female. The smoker group had higher NLR and MPV/Plt ratio (p < 0.05). PLR was significantly higher for the non-smoker group (p < 0.05). CONCLUSION: As a result of our study, an increase in the NLR which is used as a systemic inflammatory marker, a decrease in the PLR and an increase in the MPV/Plt ratio which indicates thromboembolism risk were found for the smoker group (Tab. 3, Ref. 32).

Interleukin-10 Levels and Clinical Outcome : Comparison of Retroperitoneal versus Transperitoneal Approaches in Infra-Renal Abdominal Aorta Reconstruction.

BACKGROUND: To compare retroperitoneal (RP) vs. transperitoneal (TP) approaches in abdominal aorta reconstruction in terms of operative characteristics, plasma interleukin-10 levels and postoperative complications. METHODS: A total of 100 patients scheduled for elective abdominal aortic surgery for occlusive disease under general anesthesia from May 2005 to January 2010 were included in this prospective study with allocation of patients randomly to TP approach (n = 50 ; mean (SD) age : 64.3 (4.0) years ; 76.0% were males) or RP approach (n = 50 ; mean (SD) age : 63.8 (5.6) years ; 75.0% were males) for aortic surgery. Demographic data, risk factors, perioperative and postoperative data and IL-10 levels were analyzed in two groups. RESULTS: TP approach was associated with higher levels for IL-10 measured at the time of T1 (before unclamping of aorta) [(8.4 (5.1) vs. 6.5 (4.9) pg/mL, p < 0.05)] and T2 (sixty minutes after declamping) [(11.7 (6.0) vs. 8.3 (6.2) pg/mL, p < 0.01)] compared with RP approach. Postoperative evaluation revealed a higher percentage of patients with postoperative ileus (10.0 vs. 0.0%, p < 0.001) and pulmonary complications (18.0 vs. 4.0%, p < 0.001) in the TP rather than RP groups. The TP and RP groups were similar in terms of mortality rates whereas TP approach was associated with longer mean (SD) length of hospital stay (6.2 (1.0) vs. 3.8 (1.0) days, p < 0.001) compared with the RP approach. CONCLUSIONS: Our findings revealed that the RP approach has significant advantages over the TP approach in aortic reconstruction surgery leading better pulmonary function and low ileus rate in the postoperative period as well as shorter length of hospital stay. While an increase in IL-10 levels was reported in both approaches, probably in relation to higher degree of tissue trauma, the increase was more profound in the TP approach.

Synthesis, in vitro cytotoxic and antiviral activity of cis-[Pt(R(-) and S(+)-2-alpha-hydroxybenzylbenzimidazole)2Cl2] complexes.

A pair of enantiomeric platinum(II) complexes of cis-[Pt(R(-) and S(+)-HBB)2Cl2] (HBB=2-alpha-hydroxybenzylbenzimidazole) was synthesized and evaluated for its preliminary in vitro cytotoxic activity on the human MCF-7 breast cancer and HeLa cervix cancer cell lines and antiherpes virus activity against bovine herpesvirus type 1 (BHV-1). In general, it was found that Pt(II) complexes were less cytotoxic on both cell lines than cisplatin and were comparable to carboplatin. There was no significant difference in cytotoxicity between two enantiomers, and the antiviral test results showed that the Pt(II) complexes and their carrier ligands R(-) and S(+) HBB had no effects inhibiting replication of BHV-1.

Synthesis of phosphocholine and quaternary amine ether lipids and evaluation of in vitro antineoplastic activity.

The in vitro antineoplastic activity of many phosphorus-containing (e.g., phosphocholines) and non-phosphorus-containing (e.g., quaternary ammonium salts) ether lipids has been evaluated in the HL-60 promyelocytic cell line. These compounds are analogues of ET-18-OMe (1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine). Structural modification of 1-(alkylamido)-, -(alkylthio)-, and -(alkyloxy)propyl backbones has provided further insight into the structure-activity relationships of these lipids. In this study, a long saturated C-1 chain and a three-carbon backbone with a single short C-2 substituent were preferred. At the positively charged nitrogen of phosphocholines, fewer than three substituents caused a significant loss of activity, and substituents larger than methyl decreased activity slightly. In the nonphosphorus compounds, many nitrogen heterocycles and also a sulfonium moiety were incorporated without changing the degree of activity; however, a thiazolium group decreased activity. The most active compound, 29 [N-[3-(hexadecyloxy)-2-methoxypropyl]-3-(hydroxymethyl)pyridinium bromide], was approximately twice as active as the reference standard, ET-18-OMe, in a trypan blue dye exclusion assay.

Synthesis and evaluation of novel ether lipid nucleoside conjugates for anti-HIV-1 activity.

Combinations of an amidoalkylphosphocholine, 8, and AZT have been found to cause an apparent synergistic action in suppressing infectious HIV-1 replication. In addition, amidoalkyl, oxyalkyl, and thioalkyl ether lipids have been chemically linked to anti-HIV-1 nucleosides (AZT and DDI) through phosphate and phosphonate linkages. These conjugates have shown promising in vitro anti-HIV-1 activity. Also, the conjugates have a 5-10-fold reduction in cell cytotoxicity compared to AZT alone. The most active compound, an amidoalkyl ether lipid-AZT conjugates, 4A, was found to have a differential selectivity of 1793 in a syncytial plaque assay. In comparison, AZT alone has a value of 1281.

In vitro evaluation and characterization of newly designed alkylamidophospholipid analogues as anti-human immunodeficiency virus type 1 agents.

Our laboratories first reported two novel classes of complex synthetic lipids, including alkylamidophosphocholines (PC lipid; CP-51) and alkylamidophosphate ester-linked lipid-AZT conjugates (lipid-AZT conjugates; CP-92), with selective and potent activity against human immunodeficiency virus type 1 (HIV-1). To extend these observations, we synthesized additional PC lipids and lipid-AZT conjugates (INK and INK-AZT conjugate) to evaluate their structure-activity relationships by testing for selectivity against infectious wild-type (wt) and drug-resistant HIV-1 replication, virus fusogenic activity and toxicity for mouse bone marrow cells. PC lipid compounds with medium chain lengths at positions 1 and 2 gave an improved selective index (SI). INK-3, with 12 and 8 carbons and INK-15, with 10 and 12 carbons were among the most selective when evaluated in CEM-SS cells. INK-14, a lipid-AZT conjugate where AZT replaced the choline in PC lipid INK-3, gave the highest SI of > 1250 against both infectious wt HIV-1 replication in CEM-SS cells and a clinical isolate in peripheral blood leukocytes. Notably, the PC lipid compounds INK-3 and INK-15, but not the lipid-AZT conjugate INK-14, were potent inhibitors of matched pairs of AZT-sensitive and AZT-resistant HIV-1 clinical isolates. INK-3 also inhibited replication of HIV-2 and TIBO-resistant HIV-1, and inhibited HIV-1-mediated fusogenic activity by 78, 41 and 9% in a dose-dependent manner. The TC50 for mouse bone marrow cells was > 100 micrograms/ml for INK-3 compared to 9.15-14.17 micrograms/ml for CP-51 and 0.142-0.259 microgram/ml for AZT. These data suggest that optimum PC lipid compounds are significantly less toxic than AZT and have high potential as novel therapeutic agents for AIDS.

DNA binding studies with cis-dichlorobis (5(6)-non/chlorosubstituted-2-hydroxymethyl-benzimidazole) platinum(II) complexes.

The DNA binding properties of two new platinum compounds, cis-[Pt(L)2Cl2]. 2H2O where L is 5(6)-non/chlorosubstituted-2-hydroxymethylbenzimidazole, were examined and compared with cisplatin. The platinum compounds (compounds I and II) were used to modify DNA, which was then used in electrophoretic mobility shift assays with the high mobility group (HMG)-do-main protein, HMG1. The DNA platinated with these compounds was specifically recognized by HMG1. It was concluded that the adducts formed by compounds I and II distort the DNA in a manner similar to cisplatin diadducts.

Synthesis, characterization and in vitro cytotoxic, mutagenic and antimicrobial activity of platinum(II) complexes with substituted benzimidazole ligands.

In this study, six Pt(II) complexes bearing 5(6)-H or -CH(3)-2-phenyl or -(2'-pyridyl) or -mercaptomethylbenzimidazole ligands as 'carrier groups' were synthesized and characterized by elemental analysis, IR and (1)H-NMR spectra and evaluated for their preliminary in vitro cytotoxic activity to the human RD Rhabdomyosarcoma cell line and mutagenic properties in Salmonella typhimurium strains TA 98 and TA 100 in the absence of the S9 rat liver fraction. The preliminary test results showed that the complexes had slightly greater cytotoxic activity on the RD cell line at 1 microM concentration than cisplatin. Among the compounds tested for their mutagenicity, Pt(II) complexes of 2-(2'-pyridyl)- and 5(6)-methyl-2-(2'-pyridyl)benzimidazoles were found to be mutagenic. A comparative study of the MIC (minimum inhibitory concentration) values indicated that, in general, there were no differences between the poor antimicrobial activity values of the ligands and their Pt(II) complexes with respect to the tested microorganisms. These results suggest that the synthesized Pt(II) complexes should be considered for further antitumor activity studies.

Synthesis, characterization and mutagenicity of new cis-[Pt(2-substituted-benzimidazole)2Cl2] complexes.

In this study, four new platinum(II) complexes with the structures cis-[Pt(Ligand)2Cl2] (ligand = 2-(p-methoxy-/or-p-chlorobenzyl or p-methoxyphenyl)benzimidazol (1, 2, 4 respectively) and 5(6)-methyl-2-phenoxymethylbenzimidazole (3) were synthesized and characterized by their elemental analysis, and IR and 1H NMR spectra. The potentials of the Pt(II) complexes for short-term bacterial mutagenicity were tested in reverse-mutation assays using Salmonella typhimurium frame-shift strain T 98 and S. typhimurium TA 100 and TA 102 strains, which carry mutations particularly sensitive to reversion by DNA base-pair substitution. The tests were performed in the absence of S9 rat liver fraction. Among the complexes tested 1 had no mutagenic activity. Complex 4 was found to be weakly mutagenic in TA 98 only. The Pt(II) complexes 2 and 3 were found to be mutagenic in TA 98, TA 100 and TA 102.

In vitro tuberculostatic activities of some 2-benzylbenzimidazole and 2-phenoxymethylbenzimidazole derivatives.

Some 2-benzylbenzimidazole and 2-phenoxymethylbenzimidazole derivatives were synthesized and tested for in vitro tuberculostatic activity against Mycobacterium tuberculosis H 37 Rv. and human type wild strain (protocol n degrees.4186). The synthesized compounds have one of the CH3, Cl, NO2 or OCH3 groups at position 5 and 4' and are prepared by heating appropriate o-phenylenediamines with the carboxylic acids in the presence of 4.5N HCl. The experiments indicate that 2-phenoxymethylbenzimidazoles were more active than the corresponding 2-benzylbenzimidazoles. The most active compound was 5-chloro-2-phenoxymethylbenzimidazole (IIc) (MIC: 125 micrograms/ml).