Chronic parasite infection in mice induces brain granulomas and differentially alters brain nerve growth factor levels and thermal responses in paws

Schistosoma mansoni infection, both in humans and in animal models, is known to induce granulomas in the liver and intestine. It has also been reported that in humans the eggs of this parasite can reach the brain, causing psychiatric and neuropathological disorders. Whether this also occurs in rodents is unknown. To answer this question, mice were infected with this parasite and the central nervous system (CNS) examined at various time intervals. The results show that schistosomiasis induced granulomas in several regions of the CNS and increased nerve growth factor (NGF) levels in the cortex, hypothalamus and brain stem, but not in the hippocampus. The infection also caused paw hyperalgesia, as determined by the hot-plate test, and a local increase in NGF, but not in substance P. These findings indicate that the murine model of infection can be used for studying mechanisms leading to human neuroschistosomiasis and suggest that the neuropathological disorders and the sensory deficits observed in human schistosomiasis are associated with impaired levels of NGF in the peripheral and central nervous system. Received: 18 January 1996 / Revised, accepted: 16 April 1996     

Neuroendocrine and clinical effects of transdermal 17β-estradiol in postmenopausal women

The neuroendocrine and clinical effects of transdermal 17β-estradiol (rated at 50 μg/day; TTS 50) were studied in 40 postmenopausal women; ten additional postmenopausal women did not receive any drugs. The changes in LH and rectal temperature induced by the infusion of the opioid antagonist naloxone (10 mg i.v. bolus plus 10 mg/h for 4 h) were used to evaluate the central activity of endogenous opioid peptides. TTS 50 increased opioid activity, as evidenced by the restoration of the LH response (P < 0.01) and the enhancement of the hypothermic effect (P < 0.05) of naloxone. A greater reduction in hot flushes was observed in TTS 50-treated subjects than in untreated women, with the maximal effect of TTS 50 achieved after 3 months of therapy. TTS 50 did not modify the concentrations of circulating lipids, glucose or liver enzymes but reduced the biochemical parameters indicative of bone reabsorption. Bone density of the distal radius significantly increased during TTS 50 (P < 0.02), reaching its maximum value after 6 months of therapy. Thereafter bone density declined, but more slowly than in untreated women.

Our data suggest that TTS 50 has marked neuroendocrine effects, that it diminishes the incidence of hot flushes and reduces bone demineralization. By contrast, it has a very little, if any, metabolic impact on the liver or on glucose and lipid metabolism.     

Management of status dystonicus: our experience and review of the literature.

Status dystonicus (SD) is a life threatening disorder that develops in patients with both primary and secondary dystonia, characterized by acute worsening of symptoms with generalized and severe muscle contractions. To date, no information is available on the best way to treat this disorder. We review the previously described cases of SD and two new cases are reported, one of which occurring in a child with static encephalopathy, and the other one in a patient with pantothenate kinase-associated neurodegeneration. Both patients were admitted to an intensive care unit and treated with midazolam and propofol. This approach proved to be useful in the former while the progressive nature of the dystonia of the second patient required the combination of intrathecal baclofen infusion and bilateral pallidal deep brain stimulation. We believe that a rapid and aggressive approach is justified to avoid the great morbidity and mortality which characterize SD. Our experience, combined with the data available in the literature, might permit to establish the best strategies in managing this rare and severe condition.     

Diagnostic utility of S100A1 expression in renal cell neoplasms: an immunohistochemical and quantitative RT-PCR study.

S100A1 is a calcium-binding protein, which has been recently found in renal cell neoplasms. We evaluated the diagnostic utility of immunohistochemical detection of S100A1 in 164 renal cell neoplasms. Forty-one clear cell, 32 papillary, and 51 chromophobe renal cell carcinomas, and 40 oncocytomas, 164 samples of normal renal parenchyma adjacent to the tumors and 13 fetal kidneys were analyzed. The levels of S100A1 mRNA detected by quantitative RT-PCR analysis of frozen tissues from seven clear cell, five papillary, and six chromophobe renal cell carcinomas, four oncocytomas, and nine samples of normal renal tissues adjacent to neoplasms were compared with the immunohistochemical detection of protein expression. Clear cell and papillary renal cell carcinomas showed positive reactions for S100A1 in 30 out of 41 tumors (73%) and in 30 out of 32 (94%) tumors, respectively. Thirty-seven renal oncocytomas out of 40 (93%) were positive for S100A1, whereas 48 of 51 (94%) chromophobe renal cell carcinomas were negative. S100A1 protein was detected in all samples of unaffected and fetal kidneys. S100A1 mRNA was detected by RT-PCR in all normal kidneys and renal cell neoplasms, although at very different levels. Statistical analyses comparing the different expression of S100A1 in clear cell and chromophobe renal cell carcinomas observed by immunohistochemical and RT-PCR methods showed significant values (P<0.001), such as when comparing by both techniques the different levels of S100A1 expression in chromophobe renal cell carcinomas and oncocytomas (P<0.001). Our study shows that S100A1 protein is expressed in oncocytomas, clear cell and papillary renal cell carcinomas but not in chromophobe renal cell carcinomas. Its immunodetection is potentially useful for the differential diagnosis between chromophobe renal cell carcinoma and oncocytoma. Further, S100A1 protein expression is constantly detected in the normal parenchyma of the adult and fetal kidney.     

The development of whole cell biosensors for on-line screening of herbicide pollution of surface waters

The use of mediator assisted amperometric whole-cell biosensors, monitoring microbial photosynthetic electron transfer, to screen for herbicides in intake protection by the water industry is described. Cells harvested from axenic cultures are loaded onto bacteriological filters and held against a working carbon electrode polarised against the silver chloride reference. Redox mediators are reduced by the microorganisms and then reoxidised at the working electrode resulting in a flow of current. For on-line applications the sensors are controlled by a programmable electrochemical analyser (Artek) and housed in specially designed perspex flow cells which incorporate light emitting diodes (LEDs) for photosynthetic stimulation. A range of cyanobacteria and algae have been tested, but biosensors incorporating unicellular cyanobacteria have proven the most successful. Results obtained using the cyanobacterium Synechococcus show detection levels of less than 200 ppb with response times of less than ten minutes for selected herbicides. Sensor stability in the absence of pollutant poisoning has been found to be greatly influenced by the choice of mediator. Membrane penetrating mediators such as -benzoquinone reduce sensor life to about 24 hours, while a sensor life of up to six days has been achieved with ferricyanide.     

Transcutaneous bilirubin measurement in preterm infants]

Transcutaneous bilirubinometry is an effective screening tool for neonatal jaundice in full-term babies. But its accuracy is not shown yet in preterm infants. METHODOLOGY: We carried out a prospective study in a neonatal intensive care unit. The study included 47 preterm infants. From birth, a transcutaneous bilirubin measurement (BTc) using the BiliCheck was made on the forehead of each newborn every 8 h. Blood sampling for determination of total serum bilirubin (BS) was combined with BTc: 1) if value of BTc was higher than limits values for phototherapy; 2) on the second day of life and 3) 4 hours after cessation of phototherapy. RESULTS: Mean gestational age was 30 week and mean birth weight was 1419 g. We studied 151 pairs of BTc and BS. Mean values obtained by BTc and BS were respectively 160.6+/-50 mumol/L and 190.6+/-61.4 mumol/L. A significant correlation between BTc and BS was found. But the limits of agreement were very wide. The negative predictive value (NPV) of BTc was above 90% in each group of gestational age. DISCUSSION: The need for phototherapy cannot be determined by BTc in preterm infants. But the BTc is reliable when its value is under the limits for phototherapy. CONCLUSION: With a very high incidence of neonatal jaundice (87%) in our cohort, a value of BTc under the limits for phototherapy has a good NPV in preterm infants.     

The reversal of cisplatin-protein interactions by the modulating agent WR2721 and its metabolites WR1065 and WR33278

Summary The reversibility of cisplatin-protein interactions by the modulating agent WR2721, its active thiol-metabolite WR1065, and the symmetrical disulfide WR33278 was studied using the model compounds (Pt(diethylenetriammine) monofunctionally bound to the sulfur in glutathione (Pt(dien)SG) and Pt(diethylenetriammine) monofunctionally bound to the sulfur in S-methylglutathione (Pt(dien)SMeG). Both model compounds could be quantified by high-performance liquid chromatography (HPLC) with UV detection. The Pt-cysteine-like bond in Pt(dien)SG could not be reversed by any of the WR compounds or by the strong nucleophiles thiosulfate (TS) and diethyldithiocarbamate (DDTC). However, the Ptmethionine-like bond in Pt(dien)SMeG could be reversed by WR1065, although the reversal was slow (k₂=0.142m ^–1 s^–1) as compared with that obtained using the modulating agents TS (k₂=10.1m ^–1 s^–1) and DDTC (k₂=3.66m ^–1 s^–1). WR2721 was hardly able to reverse the Pt-S bond in Pt(dien)SMeG (k₂=0.00529m ^–1 s^–1), and WR33278 showed no capacity to do so. The activity ofcis-diamminedichloroplatinum(II) (CDDP)-inactivated fumarase was not appreciably restored by any of the WR compounds (16%, 7.7%, and 0 for 20mm WR1065, WR2721, and WR33278, respectively) in contrast to the strong nucleophile DDTC (61% for 2mm DDTC). These in vitro studies provide information at the molecular level that may explain why WR2721, in contrast to DDTC, does not provide protection against cisplatin-induced nephrotoxicity when it is given after platinum-containing chemotherapy. The results support the present clinical use of WR2721 prior to the administration of platinum compounds.This study was financially supported by the Netherlands Cancer Fund (grant IKA 87-12) and by US Bioscience     

Anal polypoid tumor formation as the form of presentation of rectal gastric heterotopia]

Heterotopic gastric epithelium occurs in all portions of the alimentary tract, but it is extremely rare in the rectum. The authors report the finding of a pedunculated anal polyp in a 9-year-old girl with a six-month history of rectal bleeding. Microscopically, the polyp consisted of epithelium of the fundic type. Both the age of the patient and the finding of heterotopic epithelium of the fundic type alone supports a congenital malformation and not an inflammatory condition.     

Short-term synaptic plasticity, simulation of nerve terminal dynamics, and the effects of protein kinase C activation in rat hippocampus

Phorbol esters are hypothesised to produce a protein kinase C (PKC)-dependent increase in the probability of transmitter release via two mechanisms: facilitation of vesicle fusion or increases in synaptic vesicle number and replenishment. We used a combination of electrophysiology and computer simulation to distinguish these possibilities. We constructed a stochastic model of the presynaptic contacts between a pair of hippocampal pyramidal cells that used biologically realistic processes and was constrained by electrophysiological data. The model reproduced faithfully several forms of short-term synaptic plasticity, including short-term synaptic depression (STD), and allowed us to manipulate several experimentally inaccessible processes. Simulation of an increase in the size of the readily releasable vesicle pool and the time of vesicle replenishment decreased STD, whereas simulation of a facilitation of vesicle fusion downstream of Ca²⁺ influx enhanced STD. Because activation of protein kinase C with phorbol ester enhanced STD of EPSCs in rat hippocampal slice cultures, we conclude that an increase in the sensitivity of the release process for Ca²⁺ underlies the potentiation of neurotransmitter release by PKC.