In vitro cytotoxicity and phototoxicity of N-piperazinyl quinolone derivatives with a 2-thienyl group.

We examined the cytotoxic potential of nine N-[2-substituted-2-(2-thienyl)ethyl] piperazinyl quinolone derivatives on human oral epithelial mouth carcinoma (KB) and human squamous carcinoma (A431) cell lines. Phototoxic properties of these compounds were also evaluated by mouse 3T3 fibroblast under ultraviolet-A (UVA) irradiation. The percent of cell viability was evaluated by MTT assay. Compound 6 having a 4-[2-(phenylmethoxyimino)-2-(2-thienyl)ethyl] group attached to N4 position of piperazine ring of enoxacin showed the highest cytotoxicity potential on both A431 and KB cell lines (IC50 of 3.11+/-0.52 and 4.91+/-1.94 microg/ml, respectively). While some of the other tested compounds exhibited clear phototoxic potential in 3T3 cell line, compound 6 showed only a minor potential of phototoxicity. These findings suggest the high potential of 4-[2-(phenylmethoxyimino)-2-(2-thienyl)ethyl] derivative of enoxacin as a cytotoxic compound with low potency of phototoxic reactions. The mentioned chemical was identified to be of special interest for further characterization.     

Changes in the lipid composition and activities of isocitrate dehydrogenase and isocitrate lyase during encystation of Acanthamoeba culbertsoni strain A-1

The contents of total lipids, total sterols, total and individual phospholipids: lysophosphatidyl choline, lysophosphatidyl ethanolamine, phosphatidyl choline, phosphatidyl ethanolamine and alkali-stable phospholipids I and II, were significantly lower in mature cysts of Acanthamoeba culbertsoni strain A-1 than in trophozoites. The major constituent sterols of trophozoites, viz. ergosterol, 7-dehydrostigmasterol and 7,22,25-tridehydrostigmasterol which resolved as a single spot on thin-layer chromatography, disappeared in the cysts. When trophozoites grown in the presence of [14C]acetate were transferred to encystation medium, there was a steady decrease in the radioactivity in the lipids and acid-soluble fraction (glycogen) of the encysting cells while the radioactivity increased in the akali-insoluble fraction (cellulose). The activity of isocitrate lyase in the encysting cells steadily increased up to 24 h of encystation, followed by a slight decrease during 24-32 h, but the activity of isocitrate dehydrogenase steadily decreased up to 32 h of encystation, beyond which time no enzyme activity was detected. Inhibitors of isocitrate lyase, glycolate and maleate at 8.5 to 34 mM concentration inhibited encystation by 18-67%.     

Chromosomal anomalies in two coexistent myeloproliferative disorders

A 58-year-old male presented with fatigue, tiredness, and pruritus after hot showers and an elevated white blood cell count (20000/mm(3)). A diagnosis of polycythemia vera (PV) was made after investigation revealed a low erythropoietin and elevated leukocyte alkaline phosphatase (LAP) score; he was treated with repeated phlebotomies. Two years later he developed elevated white counts again and investigation revealed Philadelphia chromosome positive (19/20 cells) chronic myelocytic leukemia (CML). The karyotype also revealed trisomy 9 in 1 of 20 cells. He was treated with imatinib mesylate and went into clinical, hematologic, cytogenetic, and molecular remission. Repeat chromosomal analysis revealed absence of Philadelphia chromosome and BCR/ABL translocation but presence of trisomy 9. To our knowledge, this is the first reported case of coexisting PV and CML both associated with separate chromosomal abnormalities. This also raises an interesting therapeutic consideration of using concomitant imatinib mesylate and hydroxyurea.     

The role of sperm in inducing genomic changes in the implantation: An experimental study

Endometrial receptivity and implantation are important topics in reproductive sciences. No evidence was found to support sperm involvement in endometrial receptivity and its associated factors. This study aimed to explore the effect of the normal human spermatozoa–endometrium cell interaction in regulating genes in the endometrial receptivity pathway. Semen samples were collected from a healthy and fertile man; then, they were incubated with endometrial cells for 24 hr and considered as the sperm group. A group was cultured without spermatozoa and considered as a control group. About 24 hr later, cells were collected from the bottom of the culture dish. The expressions of the VEGF, FGF2, HBEGF, LIFR, EGF, LIF, MUC1, HOXA10, CSF and PGR genes were evaluated in the two groups. Statistical analysis was performed using an independent sample test. Compared with the control group, in the sperm group, the mRNA levels of PGR (p = .0451), VEGF (p = .0101), HBEGF (p = .0163), EFG (p = .0339), FGF2 (p = .012), LIF (p = .0324), LIFR (p = .0321) and HOXA10 (p = .0098) were significantly upregulated. The results showed that there is a need for the interaction between spermatozoa and endometrium for implantation and can be used for preparing uterine in in vitro fertilisation cycles.     

Draize rabbit eye test compatibility with eye irritation thresholds in humans: a quantitative structure-activity relationship analysis.

Draize rabbit eye test scores, as modified maximum average score (MMAS), for 68 pure bulk liquids were adjusted by the liquid-saturated vapor pressure P. These 68 adjusted scores, as log (MMAS/P), were shown to be completely equivalent to eye irritation thresholds (EIT), expressed as log (1/EIT), for 23 compounds in humans. Thus, for the first time the Draize eye test in rabbits for pure bulk liquids is shown to be perfectly compatible with eye irritation thresholds in humans. The total data set for 91 compounds was analyzed by the general solvation equation of Abraham. Values of log (MMAS/P) or log (1/EIT) could be fitted to a five-parameter equation with R2 = 0.936, SD = 0.433, AD = 0.000, and AAD = 0.340 over a range of 9.6 log units. When divided into a training set of 45 compounds, the corresponding equation could be used to predict the remaining 46 compounds in a test set with AD = -0.037 and AAD = 0.345 log units. Thus, the 91-compound equation can now be used to predict further EIT values to around 0.4 log units. It is suggested that the mechanism of action in the Draize test and in the human EIT involves passive transfer of the compound to a biophase that is quite polar, is a strong hydrogen bond base, a moderate hydrogen bond acid, and quite hydrophobic. The biophase does not resemble water or plasma, but resembles an organic solvent such as N-methylformamide.     

Pyloric volume: an important factor in the surgeon’s ability to palpate the pyloric “olive” in hypertrophic pyloric stenosis

Objective. The objective of this study was to determine whether the size of the pyloric mass is one of the factors in the surgeon's ability to palpate the pyloric “olive”. Materials and methods. The ultrasonographic images and medical records of 60 infants with surgically confirmed hypertrophic pyloric stenosis (HPS) were reviewed. The pyloric diameter (PD) and pyloric length (PL) were measured and the pyloric volume (PV) was calculated using the equation PV = 1/4π× (PD)²× PL. Based on the pediatric surgeon's physical examination the infants were divided into two groups: those with and those without palpable pyloric masses. Results. Infants with a palpable pyloric mass had an average pyloric volume of 3.33 ± 1.76 mm³, which was statistically larger than those whose hypertrophied pylorus could not be palpated (average volume 2.59 ± 2.07 mm³, P < 0.01). There was no statistically significant age difference between the two groups. Conclusion. Clinical skill of the examiner and other clinical aspects (patient cooperation, etc.) determine palpability of the pylorus in HPS. The size of the hypertrophied pylorus is also an important factor affecting the clinican's ability to palpate the pyloric mass. Received: 29 December 1995 Accepted: 7 June 1996     

DMAIC methodology for achieving public satisfaction with health departments in various districts of Punjab and optimizing CT scan patient load in urban city hospitals

The health care delivery system in Pakistan is in a process of rapid growth, and it consists of public and private sectors. The provincial government is preliminarily responsible for providing health care facilities within its province except in federally administered areas. In Pakistan, there are three tiers of governmental healthcare delivery systems, which comprise government, semi-government, and parastatal organizations. The purpose of this study is to understand the rapid increase in influx of patients in major city hospitals of the Punjab province. The reasons for patient flow towards the major city areas can vary, but our point of focus is mainly on those patients who are prescribed to get a computed tomography (CT) scan done for better diagnosis and early treatment, including but not limited to roadside accident cases. The study targets the define, measure, analyze, improve and control (DMAIC) problem solving approach to assess the potential cause of CT patient flow and the challenges that the health department is facing to cater to such a patient niche and process while minimizing the congestion in city government hospitals. The approach in this study summarizes with numerous quality tools like Voice of Customer (VOC) which is customer feedback, Customer Output Process Input and Supplier (COPIS) processes use for high-level process map to know what your customer value, Approver Resource Member Interested (ARMI) chart which is use to analyze the stakeholders on management of the project, evaluation with the help of fishbone diagram and house of quality, and for process improvement methodology we use the team brainstorming technique and the kaizen 5-why technique. The technique came up with an idea of a public-private partnership (PPP) project—partnership between public agency and private firm, as the health care industry in Punjab province is going through budgetary issues. In a PPP project, the Government will allocate the space to a private firm to build the facility on their own and provide quality service for CT scan diagnosis to the public of Punjab. The study identified the top 10 critical factors that the patients have expected from the government to be provided on priority. The Kaizen process improvement methodology has been adopted to provide the possible solution of government budgetary issues. The set of tools in this study can be adopted by other PPP projects to enhance the project performance.