Antiglycation activity of melatonin.

For the first time, it was found that the hormone melatonin exhibited antiglycation activity in vitro. It was shown that melatonin significantly slowed down the accumulation of fluorescent Schiff adducts formed as a result of BSA modification in the presence of high concentration of fructose. It was noted that, unlike the fructosylation reaction, melatonin did not affect the process of modification of BSA by methylglyoxal.

Large abdominal photopenic area on 99mTc-sestamibi myocardial perfusion imaging.

(99m)Tc-sestamibi myocardial perfusion imaging is frequently performed in conjunction with exercise or pharmacologic stress testing for evaluation of coronary heart disease. Interpretation of these studies includes systematic review of unprocessed rotating projectional images for evaluation of cardiac size as well as the presence of motion or attenuation artifacts. Occasionally, incidental noncardiac findings are detected on review of the projectional images.

Could it be coronary-subclavian steal syndrome?

A patient with history of coronary bypass surgery was admitted with chest discomfort and noted to have decreased left arm blood pressure. She was found to have severe subclavian artery stenosis causing coronary-subclavian steal syndrome. Subclavian stenting led to resolution of symptoms and normalization of blood pressure.

A standardized tool to measure and describe scleral colour in osteogenesis imperfecta.

Background: Blue colouration of the sclera is a distinctive feature of unknown aetiology in osteogenesis imperfecta (OI). It has value as a diagnostic marker, for distinguishing prognostically distinct subtypes of the condition, and has been reported to undergo rapid unexplained changes concurrently to fractures. Description of the feature is currently hampered by lack of a clinical tool.

Understanding the information needs of general practitioners managing a rare genetic disorder (osteogenesis imperfecta).

Background: Lack of adequate knowledge is a common problem in medicine, but is a particular problem in a rapidly advancing field like genetics. This study uses the example of a rare genetic disorder (osteogenesis imperfecta) to understand the information needs of primary care physicians (GPs).

Objectives: To determine whether a knowledge gap is recognised, how GPs currently attempt to overcome it, and what features of an information resource are preferred by GPs.

Fracture and non-fracture pain in children with osteogenesis imperfecta.

Aim: To describe and compare the characteristics of acute fracture and chronic non-fracture pain in children with osteogenesis imperfecta (OI).

Methods: A questionnaire about fracture-related pain and prospective 7-d diary about non-fracture-related pain was completed by a random sample of 35 children aged 5-18 from a UK national OI service. Main outcome measures included pain intensity, location, frequency, quality, coping strategies and analgesia use.

Pharmacokinetics and safety of an anti-vascular endothelial growth factor aptamer (NX1838) following injection into the vitreous humor of rhesus monkeys.

Purpose: The objective of this study was to determine the pharmacokinetics and safety for NX1838 following injection into the vitreous humor of rhesus monkeys.

Methods: Plasma and vitreous humor pharmacokinetics were determined following a single bilateral 0.25, 0.

An evaluation of the toxicities of 2'-fluorouridine and 2'-fluorocytidine-HCl in F344 rats and woodchucks (Marmota monax).

The toxicities of 2'-fluorouridine (2'-FU) and 2'-fluorocytidine-HCl (2'-FC) were separately evaluated in 2 species, male Fischer 344 (F334) rats and woodchucks. Particular attention was focused on the ability of these nucleosides to induce toxicities similar to those induced by the antiviral drug fialuridine (FIAU). 2'-FU or 2'-FC was administered to F344 male rats by intravenous injection at doses of 5, 50, and 500 mg/kg/day for 90 consecutive days and to male and female woodchucks at doses of 0.

Comparative efficacies of liposomal amikacin (MiKasome) plus oxacillin versus conventional amikacin plus oxacillin in experimental endocarditis induced by Staphylococcus aureus: microbiological and echocardiographic analyses.

Optimal treatment strategies for serious infections caused by Staphylococcus aureus have not been fully characterized. The combination of a beta-lactam plus an aminoglycoside can act synergistically against S. aureus in vitro and in vivo.

Regulatory decision strategy for entry of a novel biological therapeutic with a clinically unmonitorable toxicity into clinical trials: pre-IND meetings and a case example.

The following material was derived from a synthesis of case histories taken from investigational new drug (IND) applications and drug sponsors' experiences, utilizing fictionalized data to avoid any resemblance to any proprietary information; any such resemblance is accidental. These examples are used as an instructional scenario to illustrate appropriate handling of a difficult toxicology issue. In this scenario, a drug caused a toxicity in animals that was detected only by histopathologic analysis; if it were to develop in patients, no conventional clinical methods could be identified to monitor for it.

Experimental hepatitis E in pregnant rhesus monkeys: failure to transmit hepatitis E virus (HEV) to offspring and evidence of naturally acquired antibodies to HEV.

In an attempt to reproduce experimentally the fulminant hepatitis of pregnant women infected with hepatitis E virus (HEV), 4 nonpregnant and 6 pregnant rhesus monkeys in the first, second, or third trimester of pregnancy were inoculated intravenously with approximately 10(5.5) ID50 of HEV. Comparison of biochemical, histopathologic, and serologic profiles in pregnant and nonpregnant monkeys did not reveal an increase in the severity of hepatitis in the pregnant animals.

Spondyloenchondromatosis: syndromic identity and evolution of the phenotype.

We present case details and depict the phenotypic manifestations of a dwarfing skeletal dysplasia in an adolescent boy who was first seen in early childhood. His initial clinical and radiological findings resembled those of pseudoachondroplasia but these subsequently metamorphosed to an appearance which was diagnostic of spondyloenchondromatosis. It is uncertain whether this latter condition is a homogeneous entity or a group of heterogeneous disorders.

Characterization of simian immunodeficiency virus (SIV) infected AA-2 cells by SEM and immunoelectron microscopy.

The ultrastructural features of AA-2 cells infected with either of two strains of simian immunodeficiency virus (SIVMne-E11S or SIVSMM-PBj) were examined by scanning electron microscopy (SEM). Transformed CD4+ human B lymphocytes (AA-2) were inoculated with SIV and observed at 2, 4, and 7 days post-inoculation (dPI). Infected AA-2 cells were distinguished by the progressive loss of microvilli, and variable numbers of free or protruding spherical particles measuring 90-120nm in diameter along the cell surface.

Prolonged clinical latency and survival of macaques given a whole inactivated simian immunodeficiency virus vaccine.

Simian immunodeficiency virus (SIV) infection of macaques is a useful and relevant model for evaluating candidate human immunodeficiency virus (HIV) vaccines. One important feature of this model is that SIV vaccines can be evaluated for their ability to prevent infection as well as to prevent or delay the onset of AIDS. In the present study, a group of macaques was vaccinated with whole inactivated SIV and challenged with peripheral blood mononuclear cells from an SIV-infected macaque.

Immunological and virological changes associated with decline in CD4/CD8 ratios in lymphoid organs of SIV-infected macaques.

The decline in CD4/CD8 ratios in lymph nodes (LNs) of SIV macaques and HIV-infected individuals occurs later than that in blood. In a previous study, long-term SIV-infected macaques were delineated into two groups: (1) those whose LNs had normal CD4/CD8 ratios and (2) those whose LNs had low CD4/CD8 ratios. In the present investigation, LNs, spleens, and blood from these groups have been further analyzed to ascertain the cellular and virological events, particularly those involving CD8+ cells, that occur concomitantly with LN CD4% decline.

Unique lentivirus--host interactions: SIVsmmPBj14 infection of macaques.

The most virulent primate lentivirus identified to date, the simian virus SIVsmmPBj14 (SIV-PBj14), is unique not only because it causes acute disease and death within days instead of months or years, but also because of its replicative and cellular activation properties. The acute disease syndrome has many features in common with primary HIV-1 disease, but differences in the respective outcomes of these two acute lentiviral infections appear to be linked to the rapidity with which SIV-PBj14 replicates and the high titers of virus that subsequently accumulate in lymphoid tissues. The most prominent pathologic feature of SIV-PBj14 is extensive lymphoid hyperplasia of T-cell zones, especially in the gut-associated lymphoid tissue.

Titration and characterization of two rhesus-derived SIVmac challenge stocks.

Simian immunodeficiency virus infection of macaques is a model for human immunodeficiency virus infection of humans. In vivo-titrated stocks of SIV are essential for the utilization of this model for vaccine development. The elicitation of anti-human cell antibodies by some vaccines prepared in human cells and the related protective effects of the vaccine produced in human cells suggest a need for new macaque-derived SIV stocks.

HIV-1 infection in pigtailed macaques.

Four pigtailed macaques were inoculated with autologous cells expressing low levels of human immunodeficiency virus type 1 (HIV-1). During the first 10 weeks, infectious virus was recovered from peripheral blood mononuclear cells (PBMCs) and lymph nodes from three of the animals. Subsequently, HIV-1 DNA was frequently detected in uncultured PBMCs from all three animals, and virus was isolated from one of them at weeks 38 and 61.

The significance of transient left ventricular dilation during SPECT dipyridamole thallium-201 scintigraphy.

We assessed the significance of transient left ventricular dilation (TLVD) during single photon emission computed tomography (SPECT) dipyridamole thallium-201 scintigraphy (DTS) in 49 patients who underwent both DTS and diagnostic coronary arteriography. Quantitative analysis of DTS images and independent review by 3 experienced observers determined that 17 patients had TLVD and 32 patients had no TLVD. Patients with TLVD were similar to patients without TLVD with respect to age, history of myocardial infarction, coronary risk factors and occurrence of chest pain or electrocardiographic changes during DTS.

Summary report: workshop on the potential risks of antibody-dependent enhancement in human HIV vaccine trials.

Concern that ADE of HIV infection could occur in vivo, as a result of HIV immunization, has arisen for several reasons. Immune-mediated disease enhancement occurs in several human and animal viral diseases, including lentiviral diseases. Tropism for host M/M cells is a common characteristic in these diseases.

Association of interleukin-6 in the pathogenesis of acutely fatal SIVsmm/PBj-14 in pigtailed macaques.

Infection with a variant of simian immunodeficiency virus (SIVsmm/PBj-14) causes death in juvenile pigtailed macaques within 8 days of infection. The primary pathology is localized to the lymphoid tissues of the gut and spleen. Although the virus is present, the lesions are most consistent with acute reactive inflammation.

Decline in the CD4+ lymphocyte population in the blood of SIV-infected macaques is not reflected in lymph nodes.

Although loss of CD4+ lymphocytes in peripheral blood is a standard criterion for evaluating the course of HIV disease, little is known about changes within lymphoid organs, which contain the bulk (> 50%) of the body's lymphocytes. Because such studies are feasible only by using non-human primates, we have examined lymph nodes (LNs), spleen, and blood from monkeys infected with two isolates of simian immunodeficiency virus (SIV). During both the acute and chronic phases of these infections, characteristic reductions in the blood CD4+ cell levels are not reflected in LN, where the CD4+ pool remains within normal levels.