Advances in magnetic resonance imaging of lung physiology.

This review presents an overview of some recent magnetic resonance imaging (MRI) techniques for measuring aspects of local physiology in the lung. MRI is noninvasive, relatively high resolution, and does not expose subjects to ionizing radiation. Conventional MRI of the lung suffers from low signal intensity caused by the low proton density and the large degree of microscopic field inhomogeneity that degrades the magnetic resonance signal and interferes with image acquisition. However, in recent years, there have been rapid advances in both hardware and software design, allowing these difficulties to be minimized. This review focuses on some newer techniques that measure regional perfusion, ventilation, gas diffusion, ventilation-to-perfusion ratio, partial pressure of oxygen, and lung water. These techniques include contrast-enhanced and arterial spin-labeling techniques for measuring perfusion, hyperpolarized gas techniques for measuring regional ventilation, and apparent diffusion coefficient and multiecho and gradient echo techniques for measuring proton density and lung water. Some of the major advantages and disadvantages of each technique are discussed. In addition, some of the physiological issues associated with making measurements are discussed, along with strategies for understanding large and complex data sets.     

Melatonin and roentgen irradiation-induced acute radiation enteritis in Albino rats: an animal model

Background: Roentgen irradiation can affect normal cells, especially the rapidly growing ones such as the mucosal epithelial cells of the small intestine. The small intestine is the most radiosensitive gastrointestinal organ and patients receiving radiotherapy directed to the abdomen or pelvis may develop radiation enteritis. Although roentgen rays are widely used for both imaging and therapeutic purposes, our knowledge about the morphological changes associated with radiation enteritis is lacking. Hypothesis: This study tries to tests the hypothesis that “the intake of melatonin can minimize the morphological features of cell damage associated with radiation enteritis”. Objectives and methods: We performed this investigation to test our hypothesis and to examine the possible radioprotective effects of melatonin in acute radiation enteritis. To achieve these goals, an animal model consisting of 60 Albino rats was established. The animals were divided into five groups: Group 1, non‐irradiated; Group 2, X‐ray irradiated (X‐ray irradiation, 8 Grays); Group 3, X‐ray irradiated‐pretreated with solvent (ethanol and phosphate buffered saline); Group 4, non‐irradiated‐group treated with melatonin, and Group 5, X‐ray irradiated‐pretreated with melatonin. The small intestines were evaluated for gross (macroscopic), histological, morphometric (light microscopy), and ultrastructural changes (transmission electron microscopy). Results: We found morphological variations among the non‐irradiated‐group, X‐ray irradiated‐group and X‐ray irradiated‐intestines of the animals pretreated with melatonin. The development of acute radiation enteritis in X‐ray irradiated‐group (Groups 2 and 3) was associated with symptoms of enteritis (diarrhea and abdominal distention) and histological features of mucosal injury (mucosal ulceration, necrosis of the epithelial cells). There was a significant reduction of the morphometric parameters (villous count, villous height, crypt height and villous/crypt height ratio). Moreover, the ultrastructural features of cell damage were evident including: apoptosis, lack of parallel arrangement of the microvilli, loss of the covering glycocalyx, desquamation of the microvilli, vacuolation of the apical parts of the cells, dilatation of the rough endoplasmic reticulum, and damage of the mitochondrial cristae. In the non‐irradiated‐group and in X‐ray irradiated‐intestines of the animals pretreated with melatonin (Group 5), these changes were absent and the intestinal mucosal structure was preserved. Conclusion: Administration of melatonin prior to irradiation can protect the intestine against X‐rays destructive effects, i.e. radiation enteritis. The clinical applications of these observations await further studies.     

Alterations of estrogen receptors, progesterone receptors and c-erbB2 oncogene protein expression in ductal carcinomas of the breast

Estrogens are important for stimulating the growth of a large proportion of breast cancers. Progesterone plays critical roles in breast development and tumorigenesis. The c-erbB2 gene (HER-2/neu) is a proto-oncogene expressed in 10-34% of breast cancers. Its expression is associated with poor clinical outcome. The hypothesis that the progression of in situ ductal carcinoma of breast to invasive ductal carcinoma is associated with alterations of ER, PgR and HER-2/neu protein expression was tested. Of 100 mastectomy specimens examined, all contained both ductal carcinoma in situ (DCIS) and invasive ductal carcinomas (IDC) not otherwise specified (NOS). The status of ER, PgR and HER-2/neu proteins was examined by immunochemistry. ER and PgR protein expression was scored as the mean value of positively stained cells. HER-2/neu protein expression was evaluated on ts staining pattern (0, 1+, 2+ and 3+). We found variations between DCIS and IDC with significant decrease of the mean values of ER and PgR positively stained cells in high-grade (Grade 3) IDC (ER: 49.2+/-10.3 vs. 30.8+/-5.5 and PgR: 40.0+/-10.0 vs. 22.3+/-5.1 in DCIS and IDC, respectively, P<0.05). Invasive carcinomas with lymph node metastases or lymphovascular invasion or both had lower mean values of ER and PgR positively stained cells compared to those without these features. In IDC (Grade 3), HER-2/neu protein expression values (1.2+/-0.2) were significantly high compared to DCIS (0.7+/-0.3, P<0.05). In addition, HER-2/neu protein expression values were significantly higher (P<0.05) in IDC with lymph node metastases or lymphovascular invasion (1.5+/-0.3) than those without these features (0.8+/-0.2). A significantly high mean (P<0.05) of ER and PgR positively stained cells was observed in postmenopausal females compared to premenopausal women. In contrast, high HER-2/neu expression values were seen only in premenopausal females. A significant positive correlation was observed between ER and PgR receptor expression (r=0.81). A low degree inverse correlation (r=-0.24, P<0.012) was found between ER+/PgR+ tumors and HER-2/neu expression. These findings substantiate the notion that breast cancer progression is often associated with alterations of ER, PgR and HER-2/neu expression. The underlying mechanisms of these alterations are open for further investigation.     

New ultra-short acting hypnotic: synthesis, biological evaluation, and metabolic profile of ethyl 8-oxo-5,6,7,8-tetrahydro-thiazolo[3,2-a][1,3]diazepin-3-carboxylate (HIE-124)

Ethyl 8-oxo-5,6,7,8-tetrahydro-thiazolo[3,2-a][1,3]diazepin-3-carboxylate (HIE-124, 4) is a member of a new generation of ultra-short acting hypnotics. HIE-124 (4) exhibited potent in vivo activity with a rapid onset of action and a short duration of action, with no acute tolerance or noticeable side effects. The metabolic profile of 4 is also performed. HIE-124 (4) has the potential use as a preanesthetic medication, anesthesia inducer, and could be used with thiopental sodium to maintain anesthesia for longer duration.     

Microwave-assisted synthesis and antimicrobial activities of flavonoid derivatives

Eleven flavonoid derivatives were synthesised using a modified Baker-Venkataraman rearrangement, and subsequent microwave-assisted closure of the heterocyclic ring. All of the synthetic compounds displayed antifungal activity against Aspergillus niger and Fusarium oxysporium, and two of the synthetic flavonoid analogues exhibited significant activity against methicillin-resistant Staphylococcus aureus.     

Identity and transfer of male reproductive gland proteins of the dengue vector mosquito, Aedes aegypti: potential tools for control of female feeding and reproduction

Male reproductive gland proteins (mRGPs) impact the physiology and/or behavior of mated females in a broad range of organisms. We sought to identify mRGPs of the yellow fever mosquito, Aedes aegypti, the primary vector of dengue and yellow fever viruses. Earlier studies with Ae. aegypti demonstrated that "matrone" (a partially purified male reproductive accessory gland substance) or male accessory gland fluid injected into virgin female Ae. aegypti affect female sexual refractoriness, blood feeding and digestion, flight, ovarian development, and oviposition. Using bioinformatic comparisons to Drosophila melanogaster accessory gland proteins and mass spectrometry of proteins from Ae. aegypti male accessory glands and ejaculatory ducts (AG/ED) and female reproductive tracts, we identified 63 new putative Ae. aegypti mRGPs. Twenty-one of these proteins were found in the reproductive tract of mated females but not of virgin females suggesting that they are transferred from males to females during mating. Most of the putative mRGPs fall into the same protein classes as mRGPs in other organisms, although some appear to be evolving rapidly and lack identifiable homologs in Culex pipiens, Anopheles gambiae, and D. melanogaster. Our results identify candidate male-derived molecules that may have an important influence on behavior, survival, and reproduction of female mosquitoes.     

Floral data from the mid-Cenozoic of central Pakistan

Floral remains are generally rare in the fossil record of Pakistan. We present here new discoveries of mid-Cenozoic wood and pollen of Oligocene deposits from central Pakistan. The palynological sample derives from claystone stratigraphically positioned above the wood fossils, but pollen and spores as well as the wood are all of Oligocene age. The three fossil wood samples derive from the top of the lower unit of the Chitarwata Formation, and the palynological sample comes from claystone situated in the middle unit of the formation. The wood samples are described and found to represent two species of the morphotaxon Terminalioxylon (Combretaceae): T. burmense Mädel-Angeliewa and Müller-Stoll [Madel-Angeliewa, E., Müller-Stoll, W.R., 1973. Kritische Studien über fossile Combretaceen-Hölzer: über Hölzer von Typus Terminalioxylon G. Schönfeld mit einer Revision der bisher zu Evodioxylon Chiarugi gestellten Arten. Palaeontographica 142B, 117–136.] and T. sulaimanense sp. nov. These fossils are close to modern species of Terminalia, which occur in moist deciduous or semi-evergreen tropical forests. The palynological assemblage is composed of a mixture of pollen and spore types from different origins. There is a dominance of hygrophilous ferns, pines, Amaranthaceae–Chenopodiaceae–Caryophylaceae, but also the occurrence of Palmae, which are typical of tropical rainforests. This assemblage suggests that the depositional system is set in a context of nearby mountains with a minimum altitude of 2000 to 2500 m and characterized by differentiated forest belts above the tropical lowland vegetation of lower elevations. Wood, pollen and spores support the view of a fluvial environment surrounded by a tropical forested habitat. The separate stratigraphic position of the pollen assemblage above the fossil wood could explain its slightly different, more varied, palaeoenvironmental signal.