The tissue distribution and toxicokinetics of PCB-77 after a single s.c. dose of 6 mg/kg body weight was investigated in male adult rats as well as the concurrent induction of hepatic drug-metabolizing enzymes. During five days after treatment, the PCB-77 concentrations on fat weight basis in testis and in whole blood were found to be about in the same range as the concentrations in adipose tissue, whereas in liver fat PCB-77 accumulated. EROD and MROD activities were induced by about 8 and 4 times, respectively, during a period of two weeks after treatment. Concentrations in adipose tissue and in liver as well as the hepatic enzyme activities rapidly declined during the investigation period of eight weeks. An elimination half-life for PCB-77 of approximately 7-9 days was estimated.

Adipose Tissue↗

PubMedDate not supplied

Clinical studies with the new glycosylated recombinant prourokinase.

Recombinant prourokinase (r-ProUK) is a single-chain urokinase-type plasminogen activator that is produced from a mammalian cell line. It is administered as a zymogen and remains inactive until converted to the active two-chain form on the surface of a clot. The clot specificity of this agent, therefore, is conferred by the site of conversion to the active form on the surface of the clot. Two pilot studies were conducted to evaluate the safety and efficacy of r-ProUK in patients with acute myocardial infarction. In the first study, the 90-minute patency rate was 66.7% in 21 patients receiving 60 mg over 60 minutes and 72.2% in 18 patients receiving 60 mg over 90 minutes. In the second study, the 90-minute patency rates were 45.5% in the group primed with recombinant urokinase who were given 60 mg of r-ProUK infused over 60 minutes (11 patients) and 80.8% in the primed group given 60 mg infused over 90 minutes (26 patients). Only 4.6% of patients experienced severe bleeding complications, with no patient developing intracranial hemorrhage. These two studies describe the first application of r-ProUK in patients. Although two doses were selected for evaluation, the small number of patients studied did not permit the selection of one dose as superior to the other. The results, however, did indicate that r-ProUK is a very effective thrombolytic agent in achieving patency of occluded coronary arteries. It is especially effective in maintaining coronary patency, having shown only a 1.4% rate of reocclusion. Serious bleeding complications were few and no intracranial hemorrhages were noted in this group of 131 patients. Additional clinical trials will be needed to compare the efficacy of r-ProUK with that of other available thrombolytic agents.

Adult↗

PubMedDate not supplied

Ultrathin antibiotic walled microcapsules.

Ultrathin microcapsules comprised of anionic polyelectrolytes (PE) and a polycationic aminoglycoside (AmG) antibiotic drug were prepared by depositing PE/AmG multilayers on zinc oxide (ZnO) colloid particles using the layer-by-layer self-assembly technique and subsequently dissolving the ZnO templated cores. The polyelectrolytes, dextran sulfate sodium (DxS) and poly(styrenesulfonate) (PSS), were selected owing to their different backbone structure. An aminoglycoside, tobramycin sulfate (TbS), was used for studying DxS/TbS or PSS/TbS multilayer films. The multilayer growth on ZnO cores was characterized by alternating zeta potential values that were different for the DxS/TbS and PSS/TbS multilayers due to the PE chemistry and its interaction with Zn(2+) ions. Transmission and scanning electron microscopy provide evidence of PE/TbS multilayer coating on ZnO core particles. The slow acid-decomposition of the ZnO cores using weak organic acids and the presence of sufficient quantity of Zn(2+) in the dispersion were required to produce antibiotic multilayer capsules. There was no difference in the morphological characteristics of the two types of capsules; although, the yield for [PSS/TbS](5) capsules was significantly higher than for [DxS/TbS](5) capsules which was related to the physicochemical properties of DxS/TbS/Zn(2+) and PSS/TbS/Zn(2+) complexes forming the capsule wall. The TbS quantity in the multilayer films was determined using a quartz crystal microbalance and high performance liquid chromatography techniques which showed less TbS loading in both, capsules and multilayers on planar gold substrate, than the theoretical DxS:TbS or PSS:TbS stoichiometric ratio. The decomposition of the [PE/TbS](6) multilayers was fastest in physiological buffer followed by mannitol and water. The decomposition rate of the [PSS/TbS](6) multilayers was slower than [DxS/TbS](6) monolayers. The incomplete decomposition of DxS/TbS under saline conditions suggests the major role of hydrogen bonding for stability of DxS/TbS multilayers. A combination of hydrogen bonding and hydrophobic interaction between phenyl rings in PSS was responsible for PSS/TbS multilayer stability. In vivo studies in rabbits highlight the safety and sustained drug delivery potential of the PE/AmG microcapsules. The antibiotic walled ultrathin capsules presented here are suitable for sustained ophthalmic antibiotic delivery.

Aminoglycosides↗

PubMedDate not supplied

[Role of transcranial magnetic stimulation in the diagnosis of cervical root compression and cervical myelopathy].

We were interested in the question, if transcranial magnetic stimulation of nerve structure can be used in the objective description of motor impairment in humans with cervical nerve root compression and myelopathies. We could demonstrate, that paresis is combined with an increase of the latency of the evoked muscle potentials. Applications of the method in Orthopaedics and Neurosurgery involve description of motor deficits in cervical compression radiculopathy and myelopathy. Although the value of the method for orthopaedic and neurosurgical purposes is not yet clear, our experiences indicate interesting diagnostic possibilities in cervical spine diagnostics.

Cervical Vertebrae↗

PubMedDate not supplied

Microencapsulation by means of step-wise adsorption of polyelectrolytes.

Step-wise adsorption of polyelectrolytes is used for the fabrication of micro- and nanocapsules with determined size, capsule wall composition and thickness. The capsule walls made of polyelectrolyte multilayers exclude high molecular weight compounds. Assembling of lipid layers onto these polyelectrolyte capsules prevents the permeation of small dyes. Encapsulation of magnetite nanoparticles is demonstrated and the features of these novel capsules are discussed.

Adsorption↗

PubMedDate not supplied

Analysis of the cyclin-dependent kinase inhibitor p27Kip1 in muscle invasive bladder cancer.

It has been suggested that a deregulated cell cycle control contributes to the development of human malignancies due to the loss of critical antiproliferative mechanisms. The cell cycle is controlled at two checkpoints, one at the G1-S and another at the G2-M transition. Several genes including the structurally related p21WAF/CIP1 gene, the downstream mediator of the p53 tumor suppressor gene, and the p27Kip1 gene have been identified as inducers of cell cycle arrest at the G1 checkpoint when substantial DNA damage has occurred to avoid further replication of the altered genome. Recently, a heat stable 27 kDa protein, the transcript of the p27Kip1 gene, has been identified and was suggested to substantially participate in cell cycle control at the G1 checkpoint. Previous investigations have correlated decreased expression of the p27Kip1 protein with an increased biological aggressiveness of breast and small cell lung cancer. However, the molecular-genetic analysis of a variety of human malignancies including prostate cancer failed to identify any alteration at the p27Kip1 gene locus, therefore suggesting a loss of p27Kip1 protein expression to result from post-transcriptional/post-translational events or from so far unknown regulatory mechanisms. So far, bladder cancer specimens have neither been investigated for p27Kip1 alterations on the DNA level, nor has the result of molecular genetic analysis been correlated with an immunohistochemically detected expression of the gene product, the p27Kip1 protein. The present study is the first to describe p27Kip1 gene alterations on the DNA level in 3 of 42 muscle invasive bladder cancer specimens. In contrast, loss of p27Kip1 protein expression was observed in 14 of 42 (33%) tumors. According to the previously reported observation in a variety of human malignancies, in bladder cancer loss of p27Kip1 protein expression seems to result from post-transcriptional or post-translational events.

Adult↗

PubMedDate not supplied

Prognostic value of p27Kip1 and p21WAF/Cip protein expression in muscle invasive bladder cancer.

Two genes, namely p27Kip1 and p21WAF/Cip1 that reveal distinct structural homology, have been identified as inductors of cell cycle arrest at the G1-checkpoint to prevent entry of somatic cells into the S phase of the cell cycle when substantial DNA damage has occurred. It was demonstrated that the p21WAF/Cip1 gene is induced by pathways dependent and independent from a functionally intact p53 tumour suppressor protein. It has been suggested that decreased expression both of the p21WAF/Cip1 and p27Kip1 protein may contribute to the development of human malignancies due to loss of critical antiproliferative mechanisms. So far, the role of altered p21WAF/Cip1 and mainly of a decreased p27Kip1 protein expression in patients with muscle invasive bladder cancer has not been investigated. In the present study, 50 tumour specimens from 50 patients undergoing radical cystectomy (T2-T4) were investigated for different biological and clinical characteristics as possible prognostic factors: age, depth of tumour infiltration (T-stage), histological grading (G), lymph node status as well as immunohistochemical staining for the p21WAF/Cip1 and p27Kip1 proteins. The median recurrence-free survival for patients with and without retained p21WAF/Cip1 protein expression was 54 months (3-86 months) and 13 months (1-40 months), respectively (p=0.07). During univariate analysis, loss of p21WAF/Cip1 protein expression (p=0.02), T-stage (p=0.02) and histological grading (p=0.03) were significant prognostic factors for survival, among which a negative reaction for the p21WAF/Cip1 protein (p=0.02) as well as T-stage (p=0.005) remained independent significant predictors during multivariate analysis. Loss of p27Kip1 protein expression was not correlated with the recurrence-free or the overall survival of the patients. Prospective studies are needed to confirm the independent prognostic potential of cell-cycle associated proteins such as p21WAF/Cip1 in patients with muscle invasive bladder cancer. The availability of more refined prognostic factors should assist decision making regarding the value of more aggressive treatment options, such as adjuvant or neoadjuvant chemotherapy, for defined subgroups of patients.

Adult↗

PubMedDate not supplied

Predictive value of altered p27Kip1 and p21WAF/Cip1 protein expression for the clinical prognosis of patients with localized prostate cancer.

The p21WAF/Cip and the p27Kip1 genes have been identified as inductors of cell cycle arrest at the G1-checkpoint. Alterations of both genes have been suggested to be involved in the development of a variety of human malignancies due to a loss of critical antiproliferative mechanisms. To evaluate the prognostic importance of these alterations for patients with clinically localized prostate cancer, in 86 specimens (T1-T4) from 86 patients undergoing radical prostatectomy at the Department of Urology at Hannover University Medical School, were investigated. The immunohistochemical expression of the p27Kip1 and p21WAF/Cip protein was correlated to recurrence-free and long-term survival, age, depth of tumour infiltration, histological grade and lymph node status in these patients. After a median follow-up of 71 months (1-198 months), 14 of 20 (70%) patients (Group 1) with loss of p27Kip1 protein expression or a relative amount of < 10% of positively stained tumour cells developed recurrent disease in contrast to 18 of 66 (27%) patients (Group 2) with retained p27Kip1 protein expression (> or = 10% of positively stained tumour cells). The median recurrence-free survival times were 39 (4-134) months and 67 (4-198) months for patients in Groups 1 and 2 (p < 0.01), respectively. In multivariate analysis, loss of p27Kip1 protein expression was identified as the only independent prognostic parameter for recurrence-free survival. Univariate analysis (log-rank test) identified histological grading (p < 0.01) and reactivity for p27Kip1 (p = 0.046) (> or = 10% positivity) as prognostic factors for disease-specific long-term survival. However, during multivariate analysis none of the biological variables investigated retained independent prognostic importance regarding overall survival. Neither a low or a high expression of p21Waf/Cip could be correlated with the clinical prognosis of the patients following radical prostatectomy. This study confirms the independent prognostic value of decreased p27Kip1 protein expression in patients with localized prostate cancer, while a prognostic importance of p21Waf/Cip in addition to established patients' and tumour characteristics like tumour stage and histological grading appears rather unlikely.

Adenocarcinoma↗

PubMedDate not supplied

[Acrocyanosis with sphacelus of the extremities in a newborn infant].

Explore the source record for details and available documents.

Cyanosis↗