Tissue response to subcutaneous implantation of glucose-oxidase-based glucose sensors in rats

Considerable progress in improved control of disturbed glucose metabolism can be expected by continuous glucose monitoring. The aim of the study was to evaluate in male Sprague-Dawley rats tissue response to implantation of a new amperometric glucose-oxidase-based glucose sensor (NTS) compared to a commercially available sensor system CGMS of MiniMed. Both sensors were tested under working conditions over a period of 3 days. Using NTS, glucose in interstitial fluid reflected glucose in arterial blood even in rapidly changing hyper- and hypoglycaemia whereas the CGMS did not detect the experimentally induced glucose changes adequately. Gene expression profiling was performed using Affymetrix chips. Acute phase response to injury by sensor application for a short time is indicated by down regulation of the increase in mRNA of proteases e.g. metallothionein-1alpha and matrix metalloprotease-3 at day 3. Improvement of anabolic situation is suggested by decrease in mRNA of insulin-like growth factor binding protein whereas increase of heme oxygenase and hypoxia-inducible factor may be related to defense mechanisms. Changes of mRNA together with slight fibrous capsule formation suggest good histocompatibility. Comparability of the patterns of changed mRNA in tissue surrounding SCGM with and without operating voltage as shown in dendrogram indicates no contribution of hydrogen peroxide to worsening biocompatibility. Beside established histological investigations of foreign body reaction weeks or months after implantation, gene expression profiling provides additional information to biocompatibility already early after implantation.     

Insulin Receptor Isoforms A and B as well as Insulin Receptor Substrates-1 and -2 Are Differentially Expressed in Prostate Cancer

Aims/Hypothesis

In different cancers types, insulin receptor isoform composition or insulin receptor substrate (IRS) isoforms are different to healthy tissue. This may be a molecular link to increased cancer risk in diabetes and obesity. Since this is yet unclear for prostate cancer, we investigated IR isoform composition and IRS balance in prostate cancer compared to benign and tumor adjacent benign prostate tissue and brought this into relation to cell proliferation.

Methods

We studied 23 benign prostate samples from radical cystectomy or benign prostatic hyperplasia surgery, 30 samples from benign tissue directly adjacent to prostate cancer foci and 35 cancer samples from different patients. RNA expression levels for insulin receptor isoforms A and B, IRS-1, IRS-2, and IGF-1 receptor were assessed by quantitative real-time RT-PCR. In addition, RNA- and protein expression of the cell cycle regulator p27^Kip1 was quantified by real-time RT-PCR and immunohistochemistry.

Results

Insulin receptor isoform A to B ratio was significantly higher in cancer as well as in tumor adjacent benign prostate tissue compared to purely benign prostates (p<0.05). IRS-1 to IRS-2 ratios were lower in malignant than in benign prostatic tissue (p<0.05). These altered ratios both in cancer and adjacent tissue were significantly associated with reduced p27^Kip1 content (p<0.02). Interestingly, IGF-1 receptor levels were significantly lower in patients with type 2 diabetes (p = 0.0019).

Conclusions/Interpretation

We found significant differences in the insulin signaling cascade between benign prostate tissue and prostate cancer. Histological benign tissue adjacent to cancer showed expression patterns similar to the malignancies. Our findings suggest a role of the insulin signaling pathway in prostate cancer and surrounding tissue and can hence be relevant for both novel diagnostic and therapeutic approaches in this malignancy.     

Chronological relationship between eutrophication and reed decline in three lakes of southern Germany

Eutrophication is often considered to play an important role in reed decline. We decided to use a chronological comparison of the two phenomena as a useful aid in the search for a possible causal relationship between them. Eutrophication is usually documented by changes in phosphorus and nitrogen content in water but there are no such data older than 10 years available for most of the lakes in which reed decline has been observed. The entire historical record of eutrophication has been recently reconstructed from micropaleontological analysis of indicatory diatom frustules, deposited in sediments in three lakes in south Germany. In these lakes, reed decline was well documented by archival aerial photographs. The comparison of reed decline history with the reconstructed changes in water quality confirmed the coincidence of reed decline and eutrophication. Consequently, eutrophication cannot be excluded as a potential cause of reed decline in any lake in this study.     

Ring the bell for Matins: circadian adaptation to split sleep by cloistered monks and nuns

Cloistered monks and nuns adhere to a 10-century-old strict schedule with a common zeitgeber of a night split by a 2- to 3-h-long Office (Matins). The authors evaluated how the circadian core body temperature rhythm and sleep adapt in cloistered monks and nuns in two monasteries. Five monks and five nuns following the split-sleep night schedule for 5 to 46 yrs without interruption and 10 controls underwent interviews, sleep scales, and physical examination and produced a week-long sleep diary and actigraphy, plus 48-h recordings of core body temperature. The circadian rhythm of temperature was described by partial Fourier time-series analysis (with 12- and 24-h harmonics). The temperature peak and trough values and clock times did not differ between groups. However, the temperature rhythm was biphasic in monks and nuns, with an early decrease at 19:39 ± 4:30 h (median ± 95% interval), plateau or rise of temperature at 22:35 ± 00:23 h (while asleep) lasting 296 ± 39 min, followed by a second decrease after the Matins Office, and a classical morning rise. Although they required alarm clocks to wake-up for Matins at midnight, the body temperature rise anticipated the nocturnal awakening by 85 ± 15 min. Compared to the controls, the monks and nuns had an earlier sleep onset (20:05 ± 00:59 h vs. 00:00 ± 00:54 h, median ± 95% confidence interval, p= .0001) and offset (06:27 ± 0:22 h, vs. 07:37 ± 0:33 h, p= .0001), as well as a shorter sleep time (6.5 ± 0.6 vs. 7.6 ± 0.7 h, p= .05). They reported difficulties with sleep latency, sleep duration, and daytime function, and more frequent hypnagogic hallucinations. In contrast to their daytime silence, they experienced conversations (and occasionally prayers) in dreams. The biphasic temperature profile in monks and nuns suggests the human clock adapts to and even anticipates nocturnal awakenings. It resembles the biphasic sleep and rhythm of healthy volunteers transferred to a short (10-h) photoperiod and provides a living glance into the sleep pattern of medieval time.     

Sleep-Related Declarative Memory Consolidation and Verbal Replay during Sleep Talking in Patients with REM Sleep Behavior Disorder

Objective

To determine if sleep talkers with REM sleep behavior disorder (RBD) would utter during REM sleep sentences learned before sleep, and to evaluate their verbal memory consolidation during sleep.

Methods

Eighteen patients with RBD and 10 controls performed two verbal memory tasks (16 words from the Free and Cued Selective Reminding Test and a 220-263 word long modified Story Recall Test) in the evening, followed by nocturnal video-polysomnography and morning recall (night-time consolidation). In 9 patients with RBD, daytime consolidation (morning learning/recall, evening recall) was also evaluated with the modified Story Recall Test in a cross-over order. Two RBD patients with dementia were studied separately. Sleep talking was recorded using video-polysomnography, and the utterances were compared to the studied texts by two external judges.

Results

Sleep-related verbal memory consolidation was maintained in patients with RBD (+24±36% words) as in controls (+9±18%, p=0.3). The two demented patients with RBD also exhibited excellent nighttime consolidation. The post-sleep performance was unrelated to the sleep measures (including continuity, stages, fragmentation and apnea-hypopnea index). Daytime consolidation (-9±19%) was worse than night-time consolidation (+29±45%, p=0.03) in the subgroup of 9 patients with RBD. Eleven patients with RBD spoke during REM sleep and pronounced a median of 20 words, which represented 0.0003% of sleep with spoken language. A single patient uttered a sentence that was judged to be semantically (but not literally) related to the text learned before sleep.

Conclusion

Verbal declarative memory normally consolidates during sleep in patients with RBD. The incorporation of learned material within REM sleep-associated sleep talking in one patient (unbeknownst to himself) at the semantic level suggests a replay at a highly cognitive creative level.     

Leaf rust (Puccinia triticina) resistance in wheat (Triticum aestivum) cultivars grown in Northern Europe 1992-2002

Diversity of resistance to leaf rust caused by Puccinia triticina can be enhanced in wheat (Triticum aestivum) cultivars through a better knowledge of resistance genes that are present in important cultivars and germplasm. Multi-pathotype tests on 84 wheat cultivars grown in Denmark, Finland, Norway and Sweden during 1992-2002 and 39 differential testers enabled the postulation of nine known genes for seedling resistance to leaf rust. Genes Lr1, Lr2a, Lr3, Lr10, Lr13, Lr14a, Lr17, Lr23 and Lr26 were found singly or in combination in 47 of the cultivars (55.9%). The most frequently occurring genes in cultivars grown in Sweden were Lr13 (20.4%), Lr14a (14.8%) and Lr26 (14.8%). Lr14a was the most common gene in cultivars grown in Norway (18.7%), Lr13 in Denmark (35.5%) and Lr10 in Finland (20.0%). Although 28 cultivars (33.3%) exhibited a response pattern that could not be assigned to resistance genes or combinations present in the tester lines, several pathotypes carried virulence and hence these genes or combinations are of limited use. Nine cultivars (10.7%) lacked detectable seedling resistance. One cultivar was resistant to all pathotypes used in the study.