Various combinations of antihypertensive drugs: comparative assessment in elderly patients]

Our objective in this study was a comparative evaluation of efficiency of modern drug alternatives to treat peptic ulcer, based on new algorithms of diagnosis and treatment. The results obtained suggest to us that in a major proportion of cases uncomplicated duodenal ulcers might be efficiently managed in an outpatient-clinic setting even with a two-to-four week monotherapy. The best results of treatment are recordable in those groups of patients having received inhibitors of proton pump.     

DNA sequence-dependent deformability deduced from protein-DNA crystal complexes

The deformability of double helical DNA is critical for its packaging in the cell, recognition by other molecules, and transient opening during biochemically important processes. Here, a complete set of sequence-dependent empirical energy functions suitable for describing such behavior is extracted from the fluctuations and correlations of structural parameters in DNA-protein crystal complexes. These elastic functions provide useful stereochemical measures of the local base step movements operative in sequence-specific recognition and protein-induced deformations. In particular, the pyrimidine-purine dimers stand out as the most variable steps in the DNA-protein complexes, apparently acting as flexible "hinges" fitting the duplex to the protein surface. In addition to the angular parameters widely used to describe DNA deformations (i.e., the bend and twist angles), the translational parameters describing the displacements of base pairs along and across the helical axis are analyzed. The observed correlations of base pair bending and shearing motions are important for nonplanar folding of DNA in nucleosomes and other nucleoprotein complexes. The knowledge-based energies also offer realistic three-dimensional models for the study of long DNA polymers at the global level, incorporating structural features beyond the scope of conventional elastic rod treatments and adding a new dimension to literal analyses of genomic sequences.     

Bedside activated partial thromboplastin time monitoring: just a matter of time?

Hydraulic Engineering, a junior∕senior-level course, is typically taught in a lecture-based format. Lecturing as a singular teaching technique has repeatedly been shown to be ineffective. Lecturing does not advance problem-solving skills, does not require creative or critical thinking, and does not prepare students for the types of problems they will face as professional engineers. In this study, two teaching techniques, problem-based learning (PBL) and cooperative learning (CL), were used to enhance learning in the hydraulic engineering course. The goals of PBL are to provide the student with an active role in learning and to allow the student to take responsibility for learning. The goals of CL are to have students work in teams, thereby learning from both each other and the instructor, and to teach students to work together cooperatively in small groups. Methods of developing teams, projects, and other assignments were explored. The course was assessed midterm and at the end of the semester. As a result, some changes were made midsemester and other recommendations are made for the future.     

Regulation of the preovulatory gonadotropin surge by endogenous steroids

Estradiol secreted by growing ovarian follicle(s) has been considered classically to be the neural trigger for the preovulatory surge of gonadotropins. The observation that the estradiol-induced gonadotropin surge in ovariectomized rats is of lesser magnitude and duration than that found in the cycling rat at proestrus has resulted in a search for other steroid regulators. Progesterone is a major regulator of the preovulatory gonadotropin surge. It can only act in the presence of an estrogen background, which is necessary for the synthesis of progesterone receptors. In the estrogen-primed ovariectomized rat, progesterone is able to initiate and enhance the gonadotropin surge to the magnitude observed on the day of proestrus and limit it to 1 day. The physiological role of progresterone in the induction of the preovulatory gonadotropin surge has been demonstrated by the attenuation of the progesterone-induced surge and the endogenous proestrus surge by progesterone receptor antagonist RU486 and the progesterone synthesis inhibitor trilostane. The promoter region of the follicle-stimulating hormone (FHS)-beta gene contains multiple progesterone response elements and progesterone brings about FSH release as well. The reduction of progesterone in the 5 alpha-position appears to be important for the regulation of progesterone secretion. Corticosteroids appear to play a significant role in the secondary FSH surge on late proestrus and early estrus.     

Gaseous transmitters and neuroendocrine regulation

Recent work has demonstrated that the brain has the capacity to synthesize impressive amounts of the gases nitric oxide (NO) and carbon monoxide (CO). There is growing evidence that these gaseous molecules function as novel neural messengers in the brain. This article reviews the pertinent literature concerning the putative role of NO and CO as critical neurotransmitters and biological mediators of the neuroendocrine axis. Abundant evidence is presented which suggests that NO has an important role in the control of reproduction due to its ability to control GnRH secretion from the hypothalamus. NO potently stimulates GnRH secretion and also appears to mediate the action of one of the major transmitters controlling GnRH secretion, glutamate. Evidence is presented which suggests that NO stimulates GnRH release due to its ability to modulate the heme-containing enzyme, guanylate cyclase, which leads to enhanced production of the second messenger molecule, cGMP. A physiological role for NO in the preovulatory LH surge was also evidenced by findings that inhibitors and antisense oligonucleotides to nitric oxide synthase (NOS) attenuate the steroid-induced and preovulatory LH surge. CO may also play a role in stimulating GnRH secretion as heme molecules stimulate GnRH release in vitro, an effect which requires heme oxygenase activity and is blocked by the gaseous scavenger molecule, hemoglobin. Evidence is also reviewed which suggests that NO acts to restrain the hypothalamic-pituitary-adrenal (HPA) axis, as it inhibits HPA stimulation by various stimulants such as interleukin-1 beta, vasopressin, and inflammation. This effect fits a proinflammatory role of NO as it leads to suppression of the release of the anti-inflammatory corticosteroids from the adrenal. Although not as intensely studied as NO, CO has been shown to suppress stimulated CRH release and may also function to restrain the HPA axis. Evidence implicating NO in the control of prolactin and growth hormone secretion is also reviewed and discussed, as is the possible role of NO acting directly at the anterior pituitary. Taken as a whole, the current data suggest that the diffusible gases, NO and CO, act as novel transmitters in the neuroendocrine axis and mediate a variety of important neuroendocrine functions.