Obstructive sleep apnoea following rapid weight gain secondary to treatment with vigabatrin (Sabril)

To examine a possible involvement of p21 protein, an inhibitor of cyclin-dependent kinases (CDKs), in the transition from hyperplastic to hypertrophic growth of rat ventricular myocytes during the first postnatal week, we analysed day-by-day changes in the number of p21 positive cells using specific antibodies against this protein. Paraffin-embedded sections of the left ventricular myocardium were examined by means of immunoperoxidase technique and hematoxylin-eosin counterstaining. While during the first three postnatal days, the positive reaction for p21 was detected only in a small fraction of myocytes (12-20%), a sudden increase in positivity occurred on day 4 (54%) and continued till day 6 when the fraction of cells expressing p21 reached 87%. Our results show that the induction of CDK inhibitor p21 in rat ventricular myocytes is developmentally regulated. Moreover, the fact that the sudden increase in p21 positivity occurred at the same stage when the myocyte proliferation rapidly ceases, suggests that this protein is likely to be involved in mediating this key event of cardiac development.     

Effect of the nootropic agent cerebrolysin in cerebral ischemia in rats with varying behavioral reactions in the open field test

Open field tests were made on 489 white male rats to distinguish subgroups by baseline higher nervous activity (HNA) to study the effects of cerebrolysin (EBEVE, Austria) on relationships between neuronal activity and cerebral blood supply in normal cerebral circulation (CC) and in acute brain ischemia. Local CC and EEG were measured by laser doppler flowmeter and read from the same point gauge. CC/EEG index was calculated. Cerebrolysin was injected i.p. in a dose 0.3 ml/100 g body mass. Brain ischemia was provoked by occlusion of the common carotid arteries. Neurological symptoms were estimated according to the McGrow scale. Also, 24-h lethality was registered. It was confirmed that cerebrolysin, as an active nootrop, enhances EEG. This effect takes place both in intact and brain ischemia rats. It was also found that cerebrolysin has different effectiveness dependent on the animal's behavior in the open field test, that blood supply to the brain does not increase in cerebrolysin-activated HNA. In stable circulation, this was compensated due to cerebral metabolic reserve, but in intensive EEG activation, recorded by CC/EEG index, cerebrolysin reduces cerebral blood supply aggravating acute brain ischemia.     

Distinct regulatory elements control muscle-specific, fiber-type-selective, and axially graded expression of a myosin light-chain gene in transgenic mice

The fast alkali myosin light chain 1f/3f (MLC1f/3f) gene is developmentally regulated, muscle specific, and preferentially expressed in fast-twitch fibers. A transgene containing an MLC1f promoter plus a downstream enhancer replicates this pattern of expression in transgenic mice. Unexpectedly, this transgene is also expressed in a striking (approximately 100-fold) rostrocaudal gradient in axial muscles (reviewed by J. R. Sanes, M. J. Donoghue, M. C. Wallace, and J. P. Merlie, Cold Spring Harbor Symp. Quant. Biol. 57:451-460, 1992). Here, we analyzed the expression of mutated transgenes to map sites necessary for muscle-specific, fiber-type-selective, and axially graded expression. We show that two E boxes (myogenic factor binding sites), a homeodomain (hox) protein binding site, and an MEF2 site, which are clustered in an approximately 170-bp core enhancer, are all necessary for maximal transgene activity in muscle but not for fiber-type- or position-dependent expression. A distinct region within the core enhancer promotes selective expression of the transgene in fast-twitch muscles. Sequences that flank the core enhancer are also necessary for high-level activity in transgenic mice but have little influence on activity in transfected cells, suggesting the presence of regions resembling matrix attachment sites. Truncations of the MLC1f promoter affected position-dependent expression of the transgene, revealing distinct regions that repress transgene activity in neck muscles and promote differential expression among intercostal muscles. Thus, the whole-body gradient of expression displayed by the complete transgene may reflect the integrated activities of discrete elements that regulate expression in subsets of muscles. Finally, we show that transgene activity is not significantly affected by deletion or overexpression of the myoD gene, suggesting that intermuscular differences in myogenic factor levels do not affect patterns of transgene expression. Together, our results provide evidence for at least nine distinct sites that exert major effects on the levels and patterns of MLC1f expression in adult muscles.     

Interleukin 6 influences germinal center development and antibody production via a contribution of C3 complement component

Mice rendered deficient for interleukin (IL) 6 by gene targeting were evaluated for their response to T cell-dependent antigens. Antigen-specific immunoglobulin (Ig)M levels were unaffected whereas all IgG isotypes showed varying degrees of alteration. Germinal center reactions occurred but remained physically smaller in comparison to those in the wild-type mice. This concurred with the observations that molecules involved in initial signaling events leading to germinal center formation were not altered (e.g., B7.2, CD40 and tumor necrosis factor R1). T cell priming was not impaired nor was a gross imbalance of T helper cell (Th) 1 versus Th2 cytokines observed. However, B7.1 molecules, absent from wild-type counterparts, were detected on germinal center B cells isolated from the deficient mice suggesting a modification of costimulatory signaling. A second alteration involved impaired de novo synthesis of C3 both in serum and germinal center cells from IL-6-deficient mice. Indeed, C3 provided an essential stimulatory signal for wild-type germinal center cells as both monoclonal antibodies that interrupted C3-CD21 interactions and sheep anti-mouse C3 antibodies caused a significant decrease in antigen-specific antibody production. In addition, germinal center cells isolated from C3-deficient mice produced a similar defect in isotype production. Low density cells with dendritic morphology were the local source of IL-6 and not the germinal center lymphocytes. Adding IL-6 in vitro to IL-6-deficient germinal center cells stimulated cell cycle progression and increased levels of antibody production. These findings reveal that the germinal center produces and uses molecules of the innate immune system, evolutionarily pirating them in order to optimally generate high affinity antibody responses.     

Repair of rat gastric mucosa: effect of 16,16-dimethyl prostaglandin E2

Coadministration with the human immunodeficiency virus (HIV) protease inhibitor ritonavir was investigated as a method for enhancing the levels of other peptidomimetic HIV protease inhibitors in plasma. In rat and human liver microsomes, ritonavir potently inhibited the cytochrome P450 (CYP)-mediated metabolism of saquinavir, indinavir, nelfinavir, and VX-478. The structural features of ritonavir responsible for CYP binding and inhibition were examined. Coadministration of other protease inhibitors with ritonavir in rats and dogs produced elevated and sustained plasma drug levels 8 to 12 h after a single dose. Drug exposure in rats was elevated by 8- to 46-fold. A > 50-fold enhancement of the concentrations of saquinavir in plasma was observed in humans following a single codose of ritonavir (600 mg) and saquinavir (200 mg). These results indicate that ritonavir can favorably alter the pharmacokinetic profiles of other protease inhibitors. Combination regimens of ritonavir and other protease inhibitors may thus play a role in the treatment of HIV infection. Because of potentially substantial drug level increases, however, such combinations require further investigation to establish safe regimens for clinical use.     

How to apply modern scientific and technological advances to the practice of clinical gastroenterology in Vietnam

There are some differences between the spectrum of gastroenterological diseases in Vietnam compared with those of more developed countries. These may be due to different living standards, quality of nutrition, and different infection rates of intestinal parasites and hepatotropic viruses. Gastric carcinoma and hepatocellular carcinoma (HCC) are leading malignancies, while colorectal cancer is less frequent. Bile duct stones often have Ascaris eggs in the centre, and they prevail in incidence over gall-bladder stones. The majority of digestive cancers are detected at a very late stage. The Vietnamese Association of Gastroenterology aims to contribute to the development of modern gastroenterology (GE) in Vietnam, to study and apply recent advances in imaging technology, such as fibre-optic diagnostic and therapeutical endoscopy, ultrasonography, laparoscopic surgery etc. and to do further work in molecular biology. For this purpose, besides our self-reliance, we need, and ask for, support and assistance from the Japanese Society of GE (JSGE), the Asian Pacific Association of GE (APAGE) and the Organisation Mondiale de GE (OMEGE). At the same time, we suggest a choice be made among the different technologies, bearing in mind their cost-effectiveness, and to give preference to measures for the primary prevention and early detection of the diseases. Japanese experience in the early detection of gastric cancer and HCC, and in the Percutaneous Ethanol Injection Therapy (PEIT) for treatment of HCC, are highly appreciated. We recommend also a judicious and scientific combination of traditional medicine and modern technology in the research and the struggle against digestive diseases.     

Use of screening mammography and its demographic and risk determinants in women 25 to 65 years of age

BACKGROUND: To know the utilization of the screening mammography among women from 25 to 65 years old in an urban health zone, where there is not an specific screening program for breast cancer. To detect the demographic and risk determinants that are involved in the mammography screening use. SUBJECTS AND METHODS: A sample of 1,240 women were interviewed consecutively as they visited their physician. Risk factors, sociodemographic variables and use of health services were analyzed. The associated variables with the use of mammography screening were determined by univariant analysis. A multiple logistic regression model was designed to identify the variables independently associated with the use of mammography screening. RESULTS: The percentage of interviewed women who have completed at least one mammography screening in the last three years has been 10.2 +/- 3% (confidence level: 95%), 68.3% of them were under 50 years old. The variables independently associated with the use of mammography screening were: age (OR = 1.08); routine visit to the gynecologist (OR = 8.13); educational level (primary: OR = 2.44, secondary: OR = 3.66, university: OR = 7.43, no schooling: reference level); and knowledge about the benefits of mammography screening (OR = 6.15). Family history of breast cancer and the other risk factors were found not to be associated with the use of mammography screening. CONCLUSIONS: The use of mammography screening among women from 25 to 65 years is inadequate according to the age and other risk factors. Mammography screening among women with a family history of breast cancer and those over 50 years old is underused, so it would be recommended and their use increased for these women. But women under 40 years old without family history of breast cancer have to be dissuaded from undertaking such a screening.     

Growth hormone in postmenopausal women after long-term oral estrogen replacement therapy

Studies of estrogen effects on growth hormone (GH) and its pulsatile release in postmenopausal women have typically utilized estrogen replacement therapy (ERT) of relatively short duration (days to weeks). The purpose of this study was to compare GH measures from healthy postmenopausal women who were on oral ERT for 3 years or more (n = 24; mean ERT duration = 16.1 years) with women not on ERT (NERT; n = 40). Blood samples were drawn remotely every 20 min for 24 h and then analyzed for mean 24-h GH, mean GH during sleep, and mean 24-h insulin-like growth factor-I (IGF-I). GH peak analyses were also performed. Mean 24-h GH and GH during sleep were significantly higher and IGF-I was significantly lower in ERT women compared with NERT women. In addition, use of long-term ERT was associated with more GH peaks relative to women not on ERT, but no change in GH peak amplitude or area. GH was not related to age in either group. GH was strongly and negatively correlated with measures of adiposity in NERT women but not in ERT women. In conclusion, long-term oral ERT is associated with increased circulating GH and decreased IGF-I levels, even after many years of treatment.