Issue-specific Regulation of Angiotensin-Converting Enzyme by Angiotensin II and Losartan in the Rat

Angiotensin II (Ang II) may regulate the release of components of the renin-angiotensin system in a tissue-specific manner. In order to study: (1) the effect of Ang II on gene expression and tissue levels of angiotensin-converting enzyme (ACE), and (2) the mechanism of the possible Ang 11 effect, we treated normal rats with Ang II and Losartan, an angiotensin AT,-receptor antagonist. Forty normal rats received Ang II (n = 20) at a rate of 200ngkg¹ min¹ or 0.9% NaCl (n = 20) subcutaneously for 3 days using osmotic Alzet minipumps. Ten rats in both groups received Losartan (15 mg kg^-1 day^-1) in their drinking water, while the rest received tap water. ACE activity and mRNA levels were measured from pulmonary, cardiac, and renal tissue. Ang II treatment resulted in significant increases in blood pressure and heart weight, as well as an increase in plasma Ang II concentration and a decrease in plasma renin activity. Simultaneous treatment with Losartan reduced the Ang II-induced effects on blood pressure and heart weight, and attenuated the Ang II-induced decrease in plasma renin activity. Pulmonary ACE activity and mRNA levels decreased during Ang II treatment, and these effects were not modified by simultaneous treatment with Losartan. Cardiac and kidney ACE activities and mRNA levels did not change significantly during Ang II treatment, but Losartan increased cardiac ACE activity (and decreased pulmonary ACE activity). The data indicate that Ang II regulates gene expression and activity of ACE in a tissue-specific manner in the rat, an effect probably involving angiotensin receptor subtype(s) different from the AT₁,-receptor.     

Plasma vasopressin in ethanol intoxication and hangover

The effect of ethanol intoxication and hangover on immunoreactive plasma arginine vasopressin (AVP) concentration was studied in 7 healthy supine men in controlled clinical conditions. In 6 subjects plasma AVP increased above control values at the time of maximal blood ethanol Concentration. The highest AVP values were observed in the subjects having nausea and vomiting and the worst hangover symptoms. During hangover plasma AVP values were higher than the controls and the response of plasma AVP to upright posture was exaggerated. The dissociation of plasma AVP concentration and ethanol diuresis suggested that the suppression of AVP release is not the sole determinant of ethanol diuresis. The study may indicate that the toxic effects of ethanol and the severity of hangover symptoms are associated with the state of hydration and individual sensitivity of AVP triggering mechanisms.     

Cloning and characterization of the t(15;17) translocation breakpoint region in acute promyelocytic leukemia

A reciprocal chromosomal translocation, t(15;17)(q22;q11.2-12), is characteristic of acute promyelocytic leukemia (APL) of French-American-British (FAB) subtype M3, and is not associated with any other human malignancy. The non-random pattern of the APL translocations suggests that specific genes on chromosomes 15 and 17 are somehow altered or deregulated as a consequence of the rearrangement. Translocation breakpoints in APL patients provide physical landmarks that suggest an approach to isolating the APL gene(s). Genetic and physical maps constructed for the APL breakpoint region on chromosome 17 have indicated that two fully-linked DNA markers, defining loci for THRA1 and D17S80, map to opposite sides of an APL breakpoint yet reside on a common 350-kb Clal fragment. Cosmid-walking experiments to clone this APL breakpoint have revealed a 38-kilobase deletion on chromosome 17. Studies in additional APL patients have shown that the breakpoint region on chromosome 17 spans at least 80 kilobases.     

Surface characteristics of adenocarcinoma of the uterine cervix

The purpose of this study was to analyze the development and classification of cervical adenocarcinoma as seen by scanning electron microscopy (SEM) and correlate the result to morphological alterations in cervical squamous cell carcinoma and endometrial adenocarcinoma. The results showed the endocervical area to be covered by a single layer of columnar cells, some with cilia, containing numerous folds and clefts, but no real glandular structures. The surface of malignant tumors consisted of pavelike arrangements of grooves and clefts covered with blunt microvillous processes, shorter and less delicate than those found on normal columnar cells. The surface microridges of squamous cells were replaced by irregular projections in squamous malignancy and endometrial adenocarcinoma showed a more undulating endometrial appearance.     

Lack of behavioural effects following intraventricular infusion of somatostatin in the conscious goat

The effect of IV or intracerebroventricular (ICV) administration of somatostatin was studied on the behaviour of conscious goats. The doses of somatostatin infused IV were 100 and 300 μg for 30 min and 600 μg for 6 min. The dose infused ICV were 10 and 100 μg for 30 min and 600 μg for 6 min. In contrast to ealier reports on experiments with rats, no behavioural effects whatsoever were seen in goat. IV infusion of 100 to 600 μg and ICV infusion of 600 μg of somatostatin caused a definite reduction in the secretion of insulin and growth hormone, but had no effect on the concentration of blood glucose. The reason why neither IV nor ICV administration of somatostatin had any behavioural effects in the conscious goat, in contrast to the effects in rat, cannot be explained with certainty. This may be due to species specificity, to the amount of somatostatin reaching the central nervous system, or to some metabolic changes in rat but not in goat.     

Collagen formation in extracellular matrix of transplants of human transformed keratinocyte cell lines

BACKGROUND, MATERIALS AND METHODS: The role of epithelial cell growth and neoplastic transformation on collagen formation and deposition in the extracellular matrix (ECM) was analyzed by culturing immortalized human epidermal cell lines and Ras-transformed benign and malignant clones on collagen gels as transplants. The lesions were analyzed for extent of growth and morphology of epithelial and mesenchymal components as well as synthesis and deposition of different collagens. RESULTS: Immortalized cell lines required up to 5 weeks of growth for a well-organized mesenchyme to develop; transplants of Ras-transformed benign clones needed 3 weeks and transplants of highly malignant clones only 2 weeks to form an organized stroma. In transplants of immortalized cells after 2 weeks of growth newly-synthesized collagen type I and type III were deposited in the mesenchyme adjacent to the muscle, forming a mature ECM, while ECM was absent adjacent to growing, differentiated, immortalized cells. In transplants of Ras-transformed benign clones the subepithelial ECM was immature at day 14, but it was forming fibers at the same time in transplants of malignant clones. These were seen as thin irregular fibers in immunohistochemistry, ultimately organized into fibrillar structures in similar locations to active synthesis detected by in situ hybridization. Depositions of crosslinked mature type I collagen occurred later in similar locations. Type III collagen synthesis and deposition was most prominent in transplants of malignant cell clones, with degradation and destruction of the extracellular matrix around invading islets of malignant cells. CONCLUSION: The development of mesenchyme was directly related to duration of growth of transplants and degree of malignancy; mesenchyme organization was inversely related to differentiation of the epithelial cells. The results showed the usefulness of the transplant model in studies on cell and tissue growth and organization.     

Genetic study of non‐syndromic tooth agenesis through the screening of paired box 9, msh homeobox 1, axin 2, and Wnt family member 10A genes: a case‐series

Non‐syndromic tooth agenesis (NSTA) is the most common developmental anomaly in humans. Several studies have been conducted on dental agenesis and numerous genes have been identified. However, the pathogenic mechanisms responsible for NSTA are not clearly understood. We studied a group of 28 patients with sporadic NSTA and nine patients with a family history of tooth agenesis. We focused on four genes – paired box 9 (PAX9), Wnt family member 10A (WNT10A), msh homeobox 1 (MSX1), and axin 2 (AXIN2) – using direct Sanger sequencing of the exons and intron–exon boundaries. The most prevalent variants identified in PAX9 and AXIN2 genes were analyzed using the chi‐square test. The sequencing results revealed a number of variants in the AXIN2 gene, including one novel missense mutation in one patient with agenesis of a single second premolar. We also identified one variant in the AXIN2 gene as being a putative risk factor for tooth agenesis. Only one missense mutation was identified in the WNT10A gene and this mutation was found in two patients. Interestingly, WNT10A is reported as the most prevalent gene mutated in the European population with NSTA.     

Correction: Effect of nanoclay orientation on oxygen barrier properties of LbL nanocomposite coated films

Correction for ‘Effect of nanoclay orientation on oxygen barrier properties of LbL nanocomposite coated films’ by Fatma Ben Dhieb et al., RSC Adv., 2019, 9, 1632–1641.

The authors regret that the first name of the third author was misspelled in the original article. The correct author names are presented here.The Royal Society of Chemistry apologises for these errors and any consequent inconvenience to authors and readers.     

Telomere length and cardiovascular aging

Telomeres are located at the end of chromosomes. They are composed of repetitive TTAGGG tandem repeats and associated proteins of crucial importance for telomere function. Telomeric DNA is shortened by each cell division until a critical length is achieved and the cell enters senescence and eventually apoptosis. Telomeres are therefore considered a 'biological clock' of the cell. Telomerase adds nucleotides to telomeric DNA thereby contributing to telomere maintenance, genomic stability, functions, and proliferative capacity of the cell. In certain rare forms of progeria, point mutations within the telomere lead to accelerated telomere attrition and premature aging. Endogenous factors causing telomere shortening are aging, inflammation, and oxidative stress. Leukocyte telomere length (LTL) shortening is inhibited by estrogen and endogenous antioxidants. Accelerated telomere attrition is associated with cardiovascular risk factors such as age, gender, obesity, smoking, sedentary life-style, excess alcohol intake, and even mental stress. Cardiovascular (CV) diseases and CV aging are usually but not invariably associated with shorter telomeres than in healthy subjects. LTL appears to be a biomarker of CV aging, reflecting the cumulative burden of endogenous and exogenous factors negatively affecting LTL. Whether accelerated telomere shortening is cause or consequence of CV aging and disease is not clear.