Strand exchange activity of human recombination protein Rad52

Repair of double-strand breaks is essential for the maintenance of genome integrity and cell survival. In eukaryotes, double-strand-break repair by homologous recombination requires the Rad52 group of proteins. Human Rad52 protein (HsRad52)-mediated annealing of complementary strands has been studied in detail, but little has been reported on the recombinase activities of HsRad52. For this study, we purified HsRad52 from Escherichia coli. DNase I protection experiments indicated that HsRad52 binds preferentially to single-stranded DNA and protects it against digestion by DNase I. HsRad52 catalyzed D-loop formation in superhelical DNA, as well as strand exchange among oligonucleotide substrates. The formation of a stoichiometric complex between HsRad52 and single-stranded DNA was found to be critical for strand exchange activity, and the coating of both the single- and double-stranded oligonucleotides inhibited the exchange reaction.     

The sympathetic nervous system in hypertension due to unilateral renal artery stenosis in man

The contribution of neurogenic mechanisms in maintaining hypertension was investigated in 13 patients with unilateral renal artery stenosis (twelve with normal, one with grossly elevated plasma renin levels) by determining the haemodynamic and hormonal responses to the centrally acting sympatholytic agent, clonidine. The same patients were studied after captopril to determine the dependency of their blood pressure on the direct peripheral effects of angiotensin-II. Sixteen patients with essential hypertension (normal plasma renin) were additionally studied after clonidine. After clonidine, blood pressure fell markedly in patients with renal artery stenosis (17 ± 3%) and essential hypertension (18 ± 2%). In both groups, clonidine lowered cardiac output by a reduction in stroke volume and heart rate; forearm vascular resistance was unchanged but digital skin vascular resistance fell. Plasma noradrenaline levels were normal in both groups and fell after clonidine; plasma renin activity and aldosterone levels were unchanged. After captopril, blood pressure fell minimally (5 ± 3%) in renal artery stenosis patients; cardiac output fell and forearm and digital skin vascular resistance were unchanged. Plasma renin activity rose, plasma aldosterone fell and plasma noradrenaline was unchanged after captopril. In the patient with grossly elevated renin levels, blood pressure fell minimally (6%) after clonidine, but unlike others fell profoundly (37%) after captopril. We conclude that, in the majority of our renal artery stenosis patients, despite the elevated blood pressure, sympathetic nervous activity was not reduced. Central neurogenic mechanisms appear to play an important role in maintaining raised blood pressure. In the same patients the peripheral effects of angiotensin-II did not maintain vascular tone or hypertension. The ischaemic kidney has a key role however, as revascularization or nephrectomy cured or ameliorated the hypertension.     

Parents' health and demographic characteristics predict noncompliance with well-child visits

BACKGROUND: The purpose of this study was to investigate factors related to well-child visit noncompliance in an ethnically diverse family practice clinic population. METHODS: Participants included 146 parents (131 mothers and 15 fathers) of children aged 0 to 24 months who received care at a St. Paul residency clinic. Participants completed telephone surveys that asked about their demographic characteristics, attitudes toward well-child visits, whether the most recent planned well-child visit had been kept, and their own and their child's health characteristics. RESULTS: All participants thought that well-child visits were important, with immunizations being the highest rated reason for importance. Fourteen percent of parents said they had missed a recent well-child visit, mostly because they forgot. More than three fourths of parents believed visit reminders were helpful, and the preferred type of reminder was a telephone call. Noncompliance with well-child visits was associated with the parent's depressive symptoms, transportation difficulties, working at a job, having private (vs public) health insurance, and being older (vs younger). CONCLUSIONS: These results suggest that well-child visit compliance might be enhanced by visit reminders and improved access to transportation. The relationship of well-child visit noncompliance to parental depressive symptoms, if verified in other populations, points to a need for greater surveillance of children/families who do not schedule or keep well-child visits.     

Anticoagulation in atrial fibrillation: the trials and tribulations of keeping within therapeutic range

Atrial fibrillation (AF) is a growing epidemic in the developed world that has attracted much attention due to the associated risk of stroke and thromboembolism. This article discusses the application of oral anticoagulation (OAC) therapy with vitamin K antagonists (VKA) in order to reduce these risks. The article provides an overview of OAC management and highlights the need for greater efforts to increase time within therapeutic range.     

Imaging the floor of the mouth and the sublingual space

A wide range of pathologic processes may involve the floor of the mouth, the part of the oral cavity that is located beneath the tongue. They include lesions that arise uniquely in this location (eg, ranula, submandibular duct obstruction) as well as various malignancies, inflammatory processes, and vascular abnormalities that may also occur elsewhere in the head and neck. Some lesions that arise in superficial tissues such as the mucosa may be easily diagnosed at physical examination. However, computed tomography, magnetic resonance imaging, or ultrasonography may be necessary for a reliable assessment of lesion extension to deeper structures. In such cases, knowledge of the complex muscular, vascular, glandular, ductal, and neural anatomy of the region is important for accurate diagnosis and treatment planning. Familiarity with the radiologic imaging appearances of the floor of the mouth and recognition of anatomic landmarks such as the mylohyoid and hyoglossus muscles are especially useful for localizing disease within this region.     

Investigating the hydrate conversion propensity of different etoricoxib lots

The physical stability of bulk active pharmaceutical ingredients (API) is of significant scientific and regulatory concern. Carrying out physical stability testing on lots with varying rates of hydrate conversion can potentially lead to erroneous conclusions if these rate differences remain unknown and unstudied. The lot dependency of etoricoxib's rate of hemihydrate conversion was investigated and a quick discriminatory technique was developed to qualitatively assess relatively slow to rapidly converting lots. This novel technique was also used to screen potential parameters affecting the hydrate conversion rate such as particle size/surface area, amorphous content, and initial hemihydrate content. Based on qualitative X-ray powder diffraction (XRPD) and quantitative Raman data, significant effects on the rate of hydration were observed with the addition of small amounts of amorphous etoricoxib. Furthermore, it was found that the presence of hemihydrate also increased the rate of conversion by seeding anhydrous etoricoxib. This suggests that the initial presence of the hydrate form can cooperatively accelerate conversion. A better understanding of the factors affecting hydrate conversion rates resulted in the appropriate selection of storage conditions for both the bulk API and the formulated product.