Substituent Pattern Effects on the Redox Potentials of Quinone-Based Active Materials for Aqueous Redox Flow Batteries.

Quinone-based, aqueous redox flow batteries are a promising technology for large-scale, low-cost energy storage. To understand the influence of substituent and substituent pattern effects of quinone-based derivatives on the redox potential, a screening study was performed that included benzoquinone, naphtaquinone, and anthraquinone derivatives. The order of substituent influence is -OH>-Me/-OMe for decreasing the redox potential and -F<-SO3 - <-CN, -NO2 for increasing the redox potential, which is in agreement with general expectations. We found that the consideration of resonance and inductive effects design strategies of redox-active materials can be extended by the ability of intramolecular hydrogen bond formation, steric hindrance, and energetic differences of conformers for oxidized and reduced species. Due to the complexity and overlap of these effects, theoretical screening studies can provide guidance for the design of new molecular materials. In addition to the redox potential, other parameters such as stability, solubility, and kinetic rate constant or synthetic accessibility are crucial to consider.

Protein C and procollagen III peptide levels in patients with hepatic dysfunction after allogeneic hematopoietic stem cell transplantation.

Veno-occlusive disease (VOD) is one of the most serious complications following hematopoietic stem cell transplantation (HSCT) and is associated with a high mortality. We conducted a large trial on the clinical significance of protein C (PC) and procollagen III peptide (PNPIII) levels, which have been described as possible diagnostic markers of VOD. In total, 350 patients undergoing allogeneic HSCT were included. PC and PNPIII levels were analyzed prior to conditioning and weekly until 8 weeks after the HSCT. Signs of VOD and other transplantation-related complications (graft-versus-host disease (GVHD), toxicity, microangiopathic hemolytic anemia, infection) were recorded weekly throughout the trial. Patients showed a significant drop of the PC levels in VOD (70.3 vs 96.3%, P<0.001) and with increasing severity of aGVHD. Steroids increased the PC levels (69.4% vs 109.4%, P<0.001). The highest PNPIII levels were registered in patients with VOD (mean 6.3 IU/ml). Patients with aGVHD showed an elevation of PNPIII, especially patients with hepatic aGVHD. PC levels during conditioning do not predict VOD (98.5 vs 76.5%, NS). Although PC and PNPIII may play a role in the pathogenesis of VOD they cannot discriminate between complications with jaundice and are only of limited help in the differential diagnosis of VOD.

[Malignant Sertoli cell tumors of the testes]. / Maligner Sertoli-Zell-Tumor des Hodens.

Sertoli cell tumors are a rare malignancy which account for approximately 1.5 % of all testicular tumors. Although malignant Sertoli cell tumors are uncommon, they are associated with a poor prognosis. So far 36 cases of malignant courses of disease have been described. We present a patient with a lymphogenic metastasized Sertoli cell tumor, who 24 months after orchiectomy and extended retroperitoneal lymphadenectomy is relapse-free.

Different proliferative potential of rat and pig hepatocytes in pure primary culture and coculture.

In the present study we have compared the growth potential of hepatocytes from rats and pigs and the influence of cocultivation between these hepatocytes and the rat liver epitheloid cell line RL-ET-14. Proliferation, i.e., DNA synthesis, was detected by autoradiography after exposure to [3H]thymidine. Rat hepatocytes cultured at low cell density showed a very low basal growth and responded to epidermal growth factor (EGF) and insulin by a considerable increase in DNA synthesis after 48 h leading to a labeling index (LI) of 33%. Cocultivation with RL-ET-14 cells almost completely blocked the basal as well as the growth factor stimulated proliferation of the rat hepatocytes. In contrast, pig hepatocytes cultured alone showed a much greater growth potential (basal: LI 11%; insulin/EGF:LI 67%) than rat hepatocytes and were further stimulated by cocultivation (basal: LI 39%; insulin/EGF: LI 89%). Density-dependent inhibition of cell growth was less pronounced with pig hepatocytes. Even after reaching confluency, they showed further strong proliferation in pure as well as in cocultures whereas the LI of the rapidly growing clone RL-ET-14 decreased to 40%. Use of conditioned medium from RL-ET-14 cells did not mimic the growth inhibition of rat hepatocytes in coculture indicating that no soluble growth inhibitors produced by the epitheloid cells are responsible for this effect. In particular, the differences between rat and pig hepatocytes in coculture are not simply due to production of TGF-beta by the epitheloid cells since the hepatocytes from both species were inhibited by TGF-beta to a similar extent.(ABSTRACT TRUNCATED AT 250 WORDS)

Different drug metabolizing capacities in cultured periportal and pericentral hepatocytes.

Isolated and cultured periportal (PP) and pericentral (PC) hepatocytes were used for studying the acinar distribution of several phase I and phase II drug metabolizing reactions and their induction by phenobarbital (PB) and 3-methylcholanthrene (MC) or a combination thereof. Ethoxycoumarin-o-deethylase (EC 1.14.14.1) (ECOD) activity was found to predominate in PC hepatocytes even after induction with MC and PB. Metabolism of biphenyl to a monosulfated product also predominated in PC hepatocytes as did the conversion of harmine to harmine glucuronide and sulfate. In contrast, metabolism of lonazolac was not zonated. The metabolism of all three substrates declined during cultivation for 24 hr and was differentially induced (biphenyl and harmine) or not affected (lonazolac) by MC or PB. Metabolic heterogeneity was best maintained by the combination of MC and PB indicating that the zonal differences are due to a specific balance of phase I and phase II reactions. Glutathione-S-transferase (GST) activities against 1-chloro-2, 4-dinitrobenzene (CDNB) were higher in PC hepatocytes and remained so after induction with PB. In contrast, GST activities against 1,2-dichloro-4-nitrobenzene (DCNB) were almost twice as high in PP cells but equilibrated due to a spontaneous increase during cultivation, particularly in PC hepatocytes. In the presence of PB or both, MC and PB, induction of the activity against DCNB occurred exclusively in the PP hepatocytes. The distribution of the GST subunits Ya and Yb1 roughly corresponded to the pattern of GST activities against CDNB and DCNB, respectively. These results agree with earlier reports demonstrating that PP and PC hepatocytes show different patterns of phase I and phase II drug metabolizing enzymes which are maintained during short-term cultivation. In vitro induction of these activities does not result in equilibration but rather maintenance or even pronounciation of these zonal differences.

Flow cytometric findings in platelets of patients following allogeneic hematopoietic stem cell transplantation.

Following allogeneic hematopoietic stem cell transplantation (HSCT) patients may have an increased bleeding tendency in spite of a normal platelet count. Moreover, an association between chronic graft-versus-host disease (cGVHD) and a thrombophilic state has been observed. Platelet receptors and granules from 27 patients following HSCT (13 without cGVHD, 14 with cGVHD) were evaluated by flow cytometric analysis and compared to 62 healthy controls. Platelets from HSCT patients stained weakly with mepacrine indicating a reduced content of dense bodies, whereas no significant degranulation reaction of alpha granules and lysosomes was detectable. In addition, a lower surface expression of GP Ia/IIa was observed, indicating an acquired thrombocytopathy. The surface receptors are activated in HSCT patients, which could be seen by the lower surface expression of GP Ib internalized during the activation process and elevated levels of LIBS-1 and PAC-1 antibody binding. Patients with cGVHD had a seven-fold increased ratio of microparticles. This study demonstrates platelet receptor and granule defects in patients following HSCT. The key role of platelets in HSCT-associated hemostatic disorders is underscored by the high levels of circulating microparticles in cGvHD patients which might explain the thrombophilic state in these patients.

Multiple primary cancers in urologic patients. Audit of 19-year experience in Berlin and review of the literature.

During the period 1969-1988, 4,353 patients were treated for urologic cancers in the Department of Urology, Klinikum Steglitz, University Hospital of The Free University Berlin. In 144 cases (3.3%) a second primary neoplasm occurred, and in 88 cases (2.0%) the urologic cancer was the first primary tumor. The relative risk of development of a secondary primary neoplasm after the urologic primary tumor was calculated. No overall increased risk was found. In relation to certain cancer associations (bladder and prostate, kidney and prostate) the risk was increased by factor 2. In 43 percent of the cases the second primary tumor developed within half a year; the overall time span was twenty-five years.

Effect of nitric oxide-donor, linsidomine chlorhydrate, in treatment of human erectile dysfunction caused by venous leakage.

Recent experimental work has demonstrated that nitric oxide (NO) is the neurotransmitter responsible for cavernous smooth muscle relaxation. We studied the effect of a direct NO-donor, linsidomine chlorhydrate (SIN-1), in 30 patients with venous leakage confirmed by dynamic pharmacocavernosography and pharmacocavernosometry that was refractory to prostaglandin E1 (PGE1) under the assumption that the more physiologic approach might give better results. In all 30 patients, response to SIN-1 was no better, and in 22 cases it was less than the response to PGE1. No systemic or local side effects of SIN-1 were observed. SIN-1 is not superior to PGE1 in the treatment of erectile dysfunction caused by venous leakage, and failure of NO-mediated smooth muscle relaxation does not play a part in the entity, "venous leakage."

Efficacy of linsidomine chlorhydrate, a direct nitric oxide donor, in the treatment of human erectile dysfunction: results of a double-blind cross over trial.

Recent experimental work has demonstrated that nitric oxide (NO) is the neurotransmitter responsible for cavernous smooth muscle relaxation. Different studies on the performance of the direct NO-donor SIN-1 (linsidomine chlorhydrate) in patients with erectile dysfunction have come to conflicting results. We have performed a double-blind cross over trial in 40 patients with erectile dysfunction of mixed etiology comparing SIN-1, SIN-1 plus the alpha-blocker Urapidil, and prostaglandin E1 (PGE1) in order to determine the effectiveness of SIN-1. PGE1 achieved the best response, the combination of SIN-1 and Urapidil performed slightly, statistically insignificantly poorer with significantly increased side effects. SIN-1 alone performed statistically significantly (p < 0.0068) worse. SIN-1 is not a useful alternative to PGE1. The combination of SIN-1 and Urapidil performs equally as good as PGE1 but cannot be recommended due to intolerable side effects.

[Subacute and subchronic percutaneous tolerance testing (28-day and 90-day test) of epicutaneously applied dis-infectants as demonstrated by the example of peroxyethanoic acid (author's transl)]. / Subakute und subchronische percutane Verträglichkeitsprüfung im 28-und 90-Tag-Test von Desinfektionsmitteln bei epicutaner Applikation, dargestellt am Beispiel von Peroxyethansäure.

As compared to control animals, guinea-pigs to the shaved backs of which a dose of 0.16 ml of a 0.12% solution of PES/100g. of body mass had been applied twice daily for periods of 28 and 90 d, respectively (5 d of application being followed by 2 d without treatment), showed erythema, loss of hair, slower increase in mass, increased heart rate, smaller body mass/kidney mass and body mass/spleen mass ratios, increases in leucocytes, ASAT, ALAT, LDH I and LDH III. In the 28-d test, slight inflammatory symptoms of the liver, kidneys and heart were observed in the experimental animals. These symptoms were more marked in the 90-d test, granulomata in the livers being particularly striking. A pneumonia of moderate to very marked degree is suggestive of the activation of a clinically latent PES infect whereby the inflammatory alterations in the kidneys might be explained by the formation of metastases.

Fibroepithelial polyp of the renal pelvis: report of a case treated with nephron-sparing surgery and review of the literature.

This is the first report of a benign fibroepithelial polyp situated in a renal calyx where nephron-sparing surgery was performed successfully.

Bladder cancer following prostate cancer--an analysis of risk factors.

Between 1969 and 1988, 1421 men had been treated for primary adenocarcinoma of the prostate. In 14 cases subsequent primary bladder cancer was observed, as compared to 5.98 cases to be expected, thus constituting a relative risk of 2.34. Seven of these cases developed synchronously (within 6 months), with a range of up to 10 years. Aetiologically, cigarette smoking was detected as the single most important denominator, whereas family history was positive for malignancy in only two cases.

Testicular microlithiasis: case report and discussion of management under special consideration of testicular germ cell tumours.

We report a case of testicular microlithiasis in a 24-year-old man who was referred to us for evaluation of unclear ultrasonographic appearance of his testes while being examined for bilateral varicocele and epididymal cysts. Since testicular microlithiasis has been found to be associated with testicular germ cell tumours we suggest a diagnostic work-up with testis biopsy to rule out testicular intraepithelial neoplasia (so-called carcinoma in situ) in otherwise normal appearing testis.

Testicular microlithiasis and concomitant testicular intraepithelial neoplasia.

We report a case of testicular microlithiasis developing during cancer follow-up in a previously normal testicle. Biopsy revealed testicular intraepithelial neoplasia which was treated with radiotherapy. We believe that especially in cancer follow-up newly developing microlithiasis must lead to biopsy to rule out otherwise undetectable germ cell neoplasia precursor.

Ileal conduit urinary diversion 16 months before renal transplantation in a case of non-functioning lower urinary tract.

The case history of a cadaveric kidney graft recipient with complete non-functioning of the lower urinary tract is reported. An ileal conduit was formed 16 months prior to transplantation. The graft ureter was implanted into the conduit without any problems, graft functioning was excellent, and no surgical, metabolic, or infectious complications occurred during the 18-month follow-up period.

Nitric oxide donor, linsidomine chlorhydrate (SIN-1), in the diagnosis and treatment of erectile dysfunction: critical appraisal and review of the literature.

Recent experimental work has demonstrated that nitric oxide (NO) is the neutrotransmitter responsible for cavernous smooth muscle relaxation. Different studies on the performance of the direct NO-donor linsidomine chlorhydrate (SIN-1) in patients with erectile dysfunction have come to conflicting results ranging from highest praise to complete dismissal. We reviewed all published studies on the use of SIN-1 for intracorporeal injection in erectile failure including our own. To this date, 3 groups published their data. Only the uncontrolled data from Hannover claim good results. The controlled data from Hamburg and Berlin on patients with erectile failure due to venous leakage, to a mixed aetiology in a double-blind fashion and to mixed aetiology with drug increase (1 mg versus 2 mg of SIN-1) showed a significantly worse performance of SIN-1 compared to the standard drug for penile injection, prostaglandin E1. We conclude that there is no place for linsidomine chlorhydrate in either the diagnosis or the treatment of erectile dysfunction.

[Mixed gonadal dysgenesis--a rare cause of primary infertility. Report of 2 cases and review of the literature]. / Die gemischte Gonadendysgenesie--eine seltene Ursache der primären Infertilität. Bericht über 2 Fälle und Literaturüberblick.

We report on two cases of primary male infertility attributable to mixed gonadal dysgenesis. In one case the diagnosis was made when the patient was 30 years old; in the other, the 44-year-old patient had been evaluated 4 years before for erectile dysfunction, which had been treated with a penile prosthesis without the diagnosis being made. These two cases are life following exceptional in that the diagnosis was made in adult-life following an uncomplicated male adolescence.

[Effectiveness and the methods of using streptokinase in myocardial infarct and preinfarct stenocardia]. / Effektivnost' i metodika primeneniia streptokinazy u bol'nykh infarktom miokarda i predynfarktnoi stenokardiei.

The effectiveness of streptokinase treatment of patients with myocardial infarction as compared to the control group and patients given anticoagulants is analysed. It is shown that the frequency of recurrent myocardial infarctions, congestive circulatory insufficiency, shock, and thromboembolic complications is lower in the group of patients treated with streptokinase than in the control group. Streptokinase improves the course of the disease and the prognosis in patients with preinfarction angina pectoris. The effect of streptokinase is higher in the first 3--6 hours after the development of myocardial infarction and in individuals under the age of 65. The effectiveness of the treatment does not diminish when the drug is injected for a short time and in small doses (300,000--750,000 U).