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.     

Uroscopy in the 21st century: high-field NMR spectroscopy

From the experiments described, it can be seen that there are different research approaches that can be taken and these are summarized in Table 1. Whereas much scientific research is principally hypothesis led, there remains, nevertheless, an important place for exploratory research. High resolution NMR can measure, directly and simultaneously, a wide range of endogenous metabolites in biological fluids and has the unique capability of providing structural information on the metabolites detected. It has proved to be a powerful research tool with which to study inherited metabolic diseases, renal disease, drug metabolism, and toxicity, and can be used to monitor the effects of drug therapy. For instance, by using a library of experimental toxins one can map the metabolic profile of site-specific nephron injury. With this approach in man one could eventually take an unknown disease such as Balkan nephropathy and predict the initial site of tubular injury, the mode of injury and therefore the kind of toxin capable of producing that injury. NMR spectroscopic techniques are still advancing rapidly, with ever increasing sensitivity and sophistication of NMR pulse sequences to enhance structural elucidation in complex mixtures. Given the advances in directly coupled HPLC-NMR and even HPLC-NMR-mass spectroscopy it is likely that these technologies in conjunction with pattern recognition will make major contribution to our understanding of renal processes and provide new diagnostic insights in the 21st century.      

Decision support in psychiatry – a comparison between the diagnostic outcomes using a computerized decision support system versus manual diagnosis

Background  

Correct diagnosis in psychiatry may be improved by novel diagnostic procedures. Computerized Decision Support Systems (CDSS) are suggested to be able to improve diagnostic procedures, but some studies indicate possible problems. Therefore, it could be important to investigate CDSS systems with regard to their feasibility to improve diagnostic procedures as well as to save time.     

The size of a microsatellite polymorphism of the haem oxygenase 1 gene is associated with idiopathic recurrent miscarriage

Endothelial damage, impaired microvascularization and immune maladaptation have been described as aetiological factors in recurrent miscarriages. We investigated the relationship between idiopathic recurrent miscarriage (IRM) and a (GT)(n) repeat microsatellite polymorphism of the gene encoding haem oxygenase 1 (HO-1), known to modulate immune functions such as T-helper (TH) cell function and to be associated with cardiovascular disease. We investigated 162 women with IRM and 129 healthy, post-menopausal controls. The length of the HO-1 (GT)(n) microsatellite was assessed by PCR and direct sequencing in all women. Results were correlated with clinical data. The distribution of genotypes was in Hardy-Weinberg equilibrium. The HO-1 (GT)(n) microsatellite repeat numbers ranged from 13 to 37, with (GT)(23) and (GT)(30) being the most common alleles in both groups. We compared alleles consisting of < or =27 GT repeats, termed class S (short) alleles and alleles consisting of >28 GT repeats, termed class L (long) alleles. Seventy per cent of women with IRM had an S allele either in heterozygous (L/S) or homozygous (S/S) form, compared to 56% of controls (P = 0.02; OR 0.54; 95% CI 0.32-0.90). With respect to S allele frequencies, we found no significant difference among women with IRM and controls [P = 0.3; odds ratio (OR) 1.23, 95% confidence interval (CI) 0.86-1.76]. Comparing women with primary and secondary IRM, no difference with respect to the length of the HO-1 (GT)(n) microsatellite was ascertained. In summary, this is the first report on a HO-1 (GT)(n) microsatellite polymorphism among women with IRM, demonstrating that the investigated polymorphism is associated with IRM in a relatively large Caucasian population.     

Effects of histamine H1-receptor blockade on respiratory and cardiac manifestation of systemic anaphylaxis

Summary In vivo anaphylaxis is associated with respiratory distress and cardiovascular failure. The present investigation was designed to further characterize respiratory and cardiac anaphylactic events. In guinea pigs, sensitization was produced by subcutaneous application of ovalbumin together with Freund's adjuvant. Fourteen days after sensitization, the effects of an intravenous infusion of ovalbumin were tested in the anesthetized artificially ventilated guinea pigs. The renewed application of the antigen induced an initial increase of left ventricular pressure which was followed by a rapid decrease 5 min after antigenic challenge. Enddiastolic left ventricular pressure increased within 3 min, thus indicating left ventricular pump failure. In the same time range, ECG recordings uniformly showed signs of acute myocardial ischemia. In addition, heart rate steadily decreased. All animals died within 15 min. Simultaneously with cardiac anaphylactic malfunction, severe arterial hypoxia and carbon dioxide retention occurred, revealing respiratory distress.Histamine is known as a potent bronchoconstrictor via histamine H₁-receptor stimulation. Administration of H₁-recpetor antagonists to improve respiration may therefore provide further information on the contribution of pulmonary malfunction to anaphylactic cardiovascular shock. Therefore, additional experiments were performed with sensitized guinea pigs pretreated with the histamine H₁-receptor blocker mepyramine. In these experiments the antigenic challenge induced a dissociation of cardiac and respiratory manifestation of anphylaxis. Despite inhibition of hypoxia and carbon dioxide retention, left ventricular pump failure and occurrence of myocardial ischemia were delayed but not suppressed.It is concluded that histamine is an important mediator of anaphylactic respiratory distress. However, vasoactive anaphylactic mediators other than histamine are primarily involved in anaphylactic cardiac malfunction occurring during the later phase of systemic anaphylaxis.Supported by grant Fe 250/1-1 from the Deutsche Forschungsgemeinschaft (DFG).     

Lymphocyte function in experimental endemic syphilis of Syrian hamsters.

We have studied the changes in the lymph nodes, spleen and thymus that occur in inbred LSH Syrian hamsters infected with Treponema pallidum Bosnia A, the causative agent of endemic syphilis, as well as the B-cell responses of these infected animals to helper T-cell independent and dependent antigens. The lymph nodes increased significantly in weight up to 6 weeks after infection, and contained viable treponemes. No significant changes in the spleen weight were observed, and no viable treponemes could be recovered from the spleen. However, the size of the thymus decreased steadily during the course of the disease. The relative number of Ig+ cells (B cells) increased in the spleen and regional lymph nodes, whereas the relative number of T cells decreased during the course of infection. In both the spleen and lymph nodes, the relative number of macrophages increased initially and decreased thereafter in the form of a bell-shaped curve showing a peak at 4-6 weeks of infection. The ability of splenic lymphocytes from infected hamsters to mount a primary PFC response to pneumococcal polysaccharide type III (SIII), a helper T-cell independent antigen, was elevated throughout the course of infection. However, the splenic PFC response to sheep erythrocytes (SRBC), a helper T-cell dependent antigen, was increased only during the first 4 weeks of infection and progressively decreased thereafter. The PFC responses of infected lymph node lymphocytes to both SIII and SRBC were increased during the first 4 weeks and decreased thereafter. These data suggested that atrophy of the thymus seen in syphilitic infection is accompanied by the complex losses of subsets of T cells and altered B-cell functions. An early loss of suppressor T cells in both the lymph nodes and spleen occurs concomitantly with a loss of T helper cells and heterologous (treponema-unrelated) B-cell functions in the lymph nodes. Helper T cells are lost from the spleen only in the later stages of infection, whereas splenic B-cell functions remain intact throughout the course of the disease. These findings were further tested by in vitro methods where splenic and lymph node lymphocytes from infected hamsters were examined for their ability to respond to Con A in terms of the induction of antigen non-specific suppressor T cells. The mixing of Con A stimulated splenic or lymph node lymphocytes from infected hamsters was unable to inhibit the primary antibody responses of SRBC as compared to the normal control.(ABSTRACT TRUNCATED AT 400 WORDS)     

Immunohistochemical and ultrastructural analysis of a mammary cystic hypersecretory carcinoma

Cystic hypersecretory carcinoma (CHC) is a rare variant of intraductal carcinoma. A CHC in a 50-year-old woman was excised and processed for light and electron microscopy and immunohistochemistry. The tumor had a marked cystic appearance. The walls of the cysts consisted of epithelial and myoepithelial cells and a well-developed basement membrane. The epithelial cells contained well-developed rough-surfaced endoplasmatic reticulum and Golgi apparatus. Secretory granules were not detected, with the exception of a few mucus-producing cells. The secretion was predominantly homogenous, reminiscent of thyroid colloid, and demonstrated distinct PAS positivity. The cells displayed a strong labeling with epithelial membrane antigen (EMA) and EMA-positive structures were observed within the intraluminal secretion, too. Some of these were stained by alcian blue. In addition, the colloid-like material was admixed with mucus showing a filamentous internal structure and lipid droplets resulting in some heterogenity of the secretion. Intraductal micropapillary proliferation in some of the cysts and adjacent nondistended ducts was a further defining feature of the tumor. Steroid hormone receptor and Ki-67 proliferation marker immuno his Tochemistry showed scattered positivity among the tumor cells. These results are in agreement with previous observations and further clarify the nature of this low-grade in situ cancer.