Effect of antagonists of adrenergic and cholinergic receptors on ion transport in the isolated rabbit caecum wall

A hypothesis was tested in this study that antagonists of adrenergic and cholinergic receptors affect sodium and chloride ion transport in the rabbit caecum. A modified Ussing chamber was used in the experiment. It was demonstrated that isolated caecum responded to a mechanical stimulus, which consisted in gentle rinsing of the mucous surface, with changes in transepithelial electrical potential difference. An application of ion transport inhibitors, amiloride for sodium and bumetanide for chloride ions, demonstrated that both sodium and chloride ion transport in part determined the response. Pharmaceuticals that are antagonistic at neural receptors (alpha- and beta-adrenergic, nicotinic, and muscarinic), applied both for incubation and stimulation, reduced electrical potential and inhibited responses to mechanical stimuli. Basing on the results of this experiment and literature data, one can presume that analogical responses occur in vivo, and the physiological role of the autonomic system includes regulation of the thickness and consistence of mucus that separates fecal masses from the caecum walls.     

Synthesis and cardiovascular activity of new 8-alkylamino-1,3-dimethyl-7-(2-hydroxy-3- piperazinopropyl)-3,7-dihydro-1H-purine-2,6-diones

7-{2-Hydroxy-3-[4-(2-phenoxyethyl)-piperazinyl-1-yl]-propyl}-1,3-di-methyl-3,7-dihydro-1H-purine-2,6-dione dihydrochloride (2), and several of its 8-alkylamino substituted derivatives (11-17) were synthesized and tested for electrocardiographic, antiarrhythmic and hypotensive activity. Also their alpha(1)- and alpha(2)-adrenoreceptor affinities were determined. It was found that compound 2, and its analogue 15 with 8-(2-morpholin-4-yl-ethylamino) substituent displayed a strong prophylactic antiarrhythmic activity in experimentally induced arrhythmia (LD50/ED50 = 54.9 and 55.0, respectively). The hypotensive activity was observed for 8-benzylamino (11) or 8-(pyridin-2-yl-methylamino) (12) analogues. All the new derivatives (11-17) and 2 showed a weak affinity for alpha1-(Ki = 0.225-1.400 microM) and alpha2-(Ki = 0.152-4.299 microM) receptors.     

Increase of crustacean sensitivity to purified hepatotoxic cyanobacterial extracts by manipulation of experimental conditions

Toxic cyanobacterial blooms are one of the most common consequences of water eutrophication. Microbiotests with crustaceans are not expensive and are easy to prepare for screening tests. They can be applied in the determination of bioactivity and interaction between toxic substances in water, including hepatotoxins. The principal aim of this study was to modify the standard conditions in the Thamnotoxkit F trade mark and Artoxkit M in order to increase crustacean sensitivity to purified cyanobacterial extracts containing microcystins. The results reported show that exposure time, higher temperature, and presence of DMSO can increase the sensitivity of microbiotests to microcystins. The best sensitivity with the Artemia salina test was achieved after a 48-h exposure at 25 degrees C. The tests using a 24-h exposure at 27 degrees C were the most sensitive for Thamnocephalus platyurus. The test without preincubation with DMSO provided the best correlation of microcystin concentration and LC(50) for Thamnocephalus platyurus and is recommended.     

The dually perfused human placenta by Schneider method modified by Miller. I. Changes of arterial and venous pH in material and fetal blood

The study was carried out on 7 human placental cotyledons. Placental perfusions performed by Schneider method modified by Miller were conducted for 180 min. Assessment of arterial and venous pH in maternal and fetal blood was performed. There were no statistically significant differences between obtained parameters throughout the experiment. The results of this study point to the conclusion that the method can be used for assessment of other perfusion liquid parameters and introduced to subsequent experiments.     

Gastrointestinal surgery in patients with ovarian cancer

OBJECTIVES: The objectives were to assess indications as well as outcome and morbidity of gastrointestinal surgery in patients with ovarian cancer. METHODS: The study included 74 patients with primary ovarian cancer who had debulking surgery (bowel surgery) from 1987 to 2001. RESULTS: In our group postoperative residual tumor was--R0 in 15 cases (20.3%) and < or = 2 cm (R2) in 33 patients (44.6%). CONCLUSION: Gastrointestinal surgery is frequently indicated during operation in ovarian cancer. Gynecologic cancer surgeons should be trained accordingly.     

Development of the "Cell Chip": a new in vitro alternative technique for immunotoxicity testing

Predictive testing of immunotoxicity associated with chemical compounds is complicated and cannot be accomplished with a single test. As most of the existing tests for immunotoxicity employ experimental animals, there is an increasing need for alternative tests in vitro. We have developed a new system for in vitro immunotoxicity testing, which employs changes in cytokine expression observed in vitro as an endpoint indicating potential for perturbation of the immune system in vivo. This system named "fluorescent cell chip" (FCC) is based on a number of genetically modified cell lines that regulate the expression of a transgene coding for fluorescent protein enhanced green fluorescent protein (EGFP) in a similar way as they regulate expression of IL-1beta, IL-2, IL-4, IFN-gamma, IL-10, TNF-alpha, and beta-actin. Morphological and functional features of selected cell lines expressing EGFP under the control of cytokine promotors were compared with maternal cell lines and this comparison showed that critical functional features of the maternal cell lines were preserved in EGFP expressing cells. Two chemicals with known immunotoxic activities, cyclosporine A and potassium tetrachloro-platinate(II), mediated compound-specific pattern of inhibition and activation of reporter gene expression. Thus, the "fluorescent cell chip" has demonstrated potential for application as a predictive screening test for immunomodulatory activities of chemicals. The major advantage of this approach is the possibility to apply this test in high throughput screening of high number of compounds for their well defined biological activity.     

Nonoperative management of lower extremity claudication caused by a Baker's cyst: case report and review of the literature

A Baker's or popliteal cyst is a synovial cyst in the popliteal fossa arising from the knee joint. The majority of patients develop a popliteal mass that is asymptomatic, but in a small percentage of patients, complications and symptoms occur; these may not only encompass the popliteal veins and arteries but may also include cyst leakage, infection, hemorrhage, and compartment syndrome. Severe lower limb ischemia caused by a Baker's cyst is extremely rare, having been reported only six times since 1960; all patients were treated with surgical intervention. We report the case of a 29-year-old male presenting with right calf claudication caused by a Baker's cyst. The patient was managed nonoperatively with nonsteroidal anti-inflammatory agents, proper exercises, and close observation. His claudication improved progressively and had completely disappeared at 12 months of follow-up. A repeat duplex arterial study showed that increased blood flow to the right foot and the right ankle/brachial index improved to 0.97 from 0.67. Repeat ultrasonography demonstrated that the size of the cyst decreased from 4.5 x 1.5 cm to 2.8 x 0.9 cm. The patient had been followed for 20 months and remained asymptomatic in the last 8 months. We will continue to follow the patient to evaluate the long-term outcome. In summary, our own data and literature review suggest that the limb ischemia caused by Baker's cyst may be a transient condition and can be managed nonoperatively in selected patients.     

Chronic endothelin exposure inhibits connexin43 expression in cultured cortical astroglia

Severe brain lesions are accompanied by sustained increases in endothelin (ET) levels, which in turn profoundly affect brain microcirculation and neural cell function. A known response of astrocytes to acute increases in ET levels is the rapid and transient closure of gap junctions and the subsequent decrease of gap junction-mediated intercellular communication (GJIC). Because evidence exists that the loss of GJIC alters astrocytic gene expression, we analyzed the effects of chronic ET exposure on astrocytic gap junction coupling. We found that within 24 hr, cultured cortical astrocytes respond to low nanomolar concentrations (2-10 nM) of either ET-1 or ET-3 with a robust inhibition of connexin (Cx)43 expression, the major junctional protein in astrocytes, and a subsequent decline of GIJC. We further observed that in the continuous presence of ETs, Cx43 expression remained inhibited for at least 7 days. In addition, a similar decrease of Cx43 expression occurred in cultured spinal cord astrocytes maintained with ET-1 for 3 days. Applying ETs in combination with the highly selective ETA and ETB receptor antagonists, BQ123 and BQ788, respectively, revealed that the inhibitory influences on astrocytic Cx43 expression depend on activation of ETB receptors. We suggest that the observed ET-dependent inhibition of Cx43 expression and the resulting decline of GJIC might represent a major pathway by which ETs regulate astrocytic gene expression in the injured brain.