Trends in HIV prevalence among public sexually transmitted disease clinic attendees in the Western region of the United States (1989-1999)

OBJECTIVES: Using data from anonymous unlinked testing of routinely collected sera, trends in HIV are compared among sexually transmitted disease patients in 4 Western urban centers. METHODS: Between 1989 and 1999, remnant sera obtained for routine syphilis testing from 256,819 patient visits to Denver, Los Angeles, San Francisco, and Seattle clinics were tested for HIV antibodies in an unlinked survey. HIV antibody test results were linked to anonymous demographic and risk information abstracted from the medical record. RESULTS: Overall cumulative HIV seroprevalences among women and among men who had sex exclusively with women were < or = 2%, declined over time, and did not exceed 8% among those who injected drugs. In contrast, cumulative HIV seroprevalences among men who have sex with men ranged from 13% in Seattle to 30% in San Francisco and declined a mean of 2.1% (95% CI, 1.6, 2.6) to 2.8% (CI 2.6, 3.1) per year, after adjustment. CONCLUSIONS: HIV infection declined over time across counties. Relative levels of HIV differed little by demographic and behavioral risk group despite differences in the severity of each county's epidemic. Because of the unique contribution of unlinked serosurveillance studies in monitoring these trends, their reinstitution in high-risk settings should be considered.     

DNA fragmentation factor 45 knockout mice exhibit longer memory retention in the novel object recognition task compared to wild-type mice

Apoptosis is an important process in the development and function of the central nervous system (CNS). To study the role of DNA fragmentation factor 45 (DFF45/ICAD) in CNS function, we previously generated DFF45 knockout mice. We found that whereas they exhibit apparently normal CNS development, DFF45 knockout mice exhibit an increased number of granule cells in the dentate gyrus and enhanced spatial learning and memory compared to wild-type mice in a Morris water maze test. In this study, we examined the performance of the DFF45 knockout mice in a novel object recognition task to measure short-term nonspatial memory that is believed to depend on the hippocampal formation. Both wild-type and DFF45 knockout mice exhibited novel object recognition 1 h posttraining. However, whereas wild-type mice no longer did so, DFF45 knockout mice were still able to differentiate the novel versus the familiar object 3 h posttraining. The longer memory retention in DFF45 knockout mice did not last up to 24 h as neither wild-type nor DFF45 knockout mice demonstrated novel object recognition 24 h posttraining. These results suggest that a lack of DFF45 facilitates hippocampus-dependent nonspatial memory, as well as hippocampus-dependent spatial memory.     

Chemical resistance of the gram-negative bacteria to different sanitizers in a water purification system

Background  

Purified water for pharmaceutical purposes must be free of microbial contamination and pyrogens. Even with the additional sanitary and disinfecting treatments applied to the system (sequential operational stages), Pseudomonas aeruginosa, Pseudomonas fluorescens, Pseudomonas alcaligenes, Pseudomonas picketti, Flavobacterium aureum, Acinetobacter lowffi and Pseudomonas diminuta were isolated and identified from a thirteen-stage purification system. To evaluate the efficacy of the chemical agents used in the disinfecting process along with those used to adjust chemical characteristics of the system, over the identified bacteria, the kinetic parameter of killing time (D-value) necessary to inactivate 90% of the initial bioburden (decimal reduction time) was experimentally determined.     

Prenatal exposure to PCBs in Cyp1a2 knock‐out mice interferes with F1 fertility,impairs long‐term potentiation,reduces acoustic startle and impairs conditioned freezing contextual memory with minimal transgenerational effects

Polychlorinated biphenyls (PCBs) are toxic environmental pollutants. Humans are exposed to PCB mixtures via contaminated food or water. PCB exposure causes adverse effects in adults and after exposure in utero. PCB toxicity depends on the congener mixture and CYP1A2 gene activity. For coplanar PCBs, toxicity depends on ligand affinity for the aryl hydrocarbon receptor (AHR). Previously, we found that perinatal exposure of mice to a three‐coplanar/five‐noncoplanar PCB mixture induced deficits in novel object recognition and trial failures in the Morris water maze in Cyp1a2^?/?::Ahr^b1 C57BL6/J mice compared with wild‐type mice (Ahr^b1 = high AHR affinity). Here we exposed gravid Cyp1a2^?/?::Ahr^b1 mice to a PCB mixture on embryonic day 10.5 by gavage and examined the F₁ and F₃ offspring (not F₂). PCB‐exposed F₁ mice exhibited increased open‐field central time, reduced acoustic startle, greater conditioned contextual freezing and reduced CA1 hippocampal long‐term potentiation with no change in spatial learning or memory. F₁ mice also had inhibited growth, decreased heart rate and cardiac output, and impaired fertility. F₃ mice showed few effects. Gene expression changes were primarily in F₁ PCB males compared with wild‐type males. There were minimal RNA and DNA methylation changes in the hippocampus from F₁ to F₃ with no clear relevance to the functional effects. F₀ PCB exposure during a period of rapid DNA de‐/remethylation in a susceptible genotype produced clear F₁ effects with little evidence of transgenerational effects in the F₃ generation. While PCBs show clear developmental neurotoxicity, their effects do not persist across generations for effects assessed herein.     

Surgical delivery of drug releasing poly(lactic-co-glycolic acid)/poly(ethylene glycol) paste with in vivo effects against glioblastoma

Introduction

The median survival of patients with glioblastoma multiforme (astrocytoma grade 4) remains less than 18 months despite radical surgery, radiotherapy and systemic chemotherapy. Surgical implantation of chemotherapy eluting wafers into the resection cavity has been shown to improve length of survival but the current licensed therapy has several drawbacks. This paper investigates in vivo efficacy of a novel drug eluting paste in glioblastoma.

Methods

Poly(lactic-co-glycolic acid)/poly(ethylene glycol) (PLGA/PEG) self-sintering paste was loaded with the chemotherapeutic agent etoposide and delivered surgically into partially resected tumours in a flank murine glioblastoma xenograft model.

Results

Surgical delivery of the paste was successful and practical, with no toxicity or surgical morbidity to the animals. The paste was retained in the tumour cavity, and preliminary results suggest a useful antitumour and antiangiogenic effect, particularly at higher doses. Bioluminescent imaging was not affected significantly by the presence of the paste in the tumour.

Conclusions

Chemotherapy loaded PLGA/PEG paste seems to be a promising technology capable of delivering active drugs into partially resected tumours. The preliminary results of this study suggest efficacy with no toxicity and will lead to larger scale efficacy studies in orthotopic glioblastoma models.     

Effect of methamphetamine on glutamate-positive neurons in the adult and developing rat somatosensory cortex

The neurotoxic effects of methamphetamine (MA) on dopaminergic and serotonergic terminals have been well-documented. Another neurotoxic effect of MA is neuronal degeneration in the somatosensory cortex, as seen by silver staining. The neurochemical characteristics of these degenerating neurons are unknown. Using glutamate and glial fibrillary acid protein (GFAP) immunohistochemistry, it was found that MA exposure in adult rats (10 mg/kg given 4 times intraperotoneally(i.p.) at 2-h intervals) causes localized depletion of glutamate-positive neurons and astrogliosis in the somatosensory cortex 3 days following treatment. The affected region covered the middle one-third portion from the longitudinal fissure to the rhinal sulcus and was predominately seen in layers II-III of the cortex. This pattern of depletion is consistent with that demonstrated previously with silver staining following MA, d-amphetamine, and 3,4-methylenedioxymethamphetmine (MDMA) exposures. Comparable effects were not found in developing animals at ages previously shown to also be resistant to MA-induced effects on dopaminergic terminals (age 20 and 40 days). Results suggest that MA exposure induces degeneration of glutamatergic neurons in the somatosensory cortex of adult rats. © 1996 Wiley-Liss, Inc.     

Effects of pyrithiamin and oxythiamin on acetylcholine levels and utilization in rat brain

VORHEES, C. V., D. E. SCHMIDT AND R. J. BARRETT. Effects of pyrithiamin and oxythiamin on acetylcholine levelsand utilization in rat brain. BRAIN RES. BULL. 3(5) 493–496, 1978.—Regional cerebral acetylcholine (ACh) levels and utilization rate were assessed in vivo in rats rendered thiamin deficient using the thiamin antagonists pyrithiamin or oxythiamin. ACh levels were significantly reduced in all brain regions of pyrithiamin treated rats and in the medulla-pons and striatum of oxythiamin treated rats compared to controls. ACh utilization was significantly reduced in the midbrain, striatum and hippocampus of pyrithiamin treated rats, but was reduced only in the striatum of oxythiamin treated rats compared to controls. Thus, there are some reductions in ACh levels and utilization that are unique to pyrithiamin induced deficiency and as such are distinct from oxythiamin/undernutrition related reductions. Since only pyrithiamin produces neurological symptoms, its unique ACh effects may be related to these symptoms.     

A developmental test battery for neurobehavioral toxicity in rats: A preliminary analysis using monosodium glutamate calcium carrageenan,and hydroxyurea

A test battery for evaluating developmental neurobehavioral toxicity was designed to attempt to meet both the general requirements of a sound test system, namely, comprehensiveness, usability, and sensitivity and the specific requirements promulgated by Britain, France, and Japan as part of their reproductive guidelines for new drugs. Monosodium glutamate (MSG) and calcium carrageenan (CC) were used to obtain preliminary data with this test battery using continuous dietary exposure from prior to conception through 90 days of postnatal life. Observations were made on reproduction and on the physical and behavioral development of the offspring. Three dose levels were used with each of the food additives and the data from these subjects were compared to data from normally fed (negative) controls and a positive control group exposed to 550 mg/kg of hydroxyurea on the 12th day of gestation. Differences between MSG and negative control groups were observed in swimming development, open field, active and passive avoidance testing. Effects observed in the CC groups were inconsistent and not dose related. Prenatal treatment with hydroxyurea produced delayed startle and swimming development and reduced open field rearing activity. This pattern of effects was less than expected indicating that hydroxyurea is an adequate, but not optimal, positive control manipulation. It appears that the test protocol used in this research could, with some modification, serve as a usable screening technique for developmental neurobehavioral toxicity.