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The article considers the conversion of carpool lanes into high-occupancy toll (HOT) lanes as an option to address downtown traffic in the U.S. According to the "2010 Annual Urban Mobility Report" from the Texas Transportation Institute at Texas A&M University, traffic congestion burns extra fossil fuels and generates heavy carbon emissions. Kirk Avila of the Orange County Transportation Authority (OCTA) said diverting vehicles into HOT lanes should speed up traffic in all lanes.

The article focuses on the efforts of chief information officers (CIOs) in U.S.-based local governments to explore collaborative software licensing arrangements with vendors. To cut software costs and earn revenues for the local government, such arrangement include selling in-house developed applications to other municipalities and hosting their databases without any additional licensing fees. As a vendor, Microsoft has developed the "mobility licensing" policy that allows customers to transfer existing licenses to other hosting environments.

The paper describes the georeferencing part of an airborne hyperspectral imaging system based on pushbroom scanning. Using ray-tracing methods from computer graphics and a highly efficient representation of the digital elevation model (DEM), georeferencing of high resolution pushbroom images runs in real time by a large margin. By adapting the georeferencing to match the DEM resolution, the camera field of view and the flight altitude, the method has potential to provide real time georeferencing, even for HD video on a high resolution DEM when a graphics processing unit (GPU) is used for processing.

The article discusses a trend popularized by the District of Columbia's Apps for Democracy contest challenging programmers to use open data published by U.S. government agencies to make useful applications (apps) for the public. Offering 35,000 U.S. dollars in prizes, the district reportedly got back 2.3 million in apps, initiating a trend. It presents views from experts and contest winners, with some questioning the strategy's usefulness after 3 years. Apps include Brian Sobel's iLive.at, Daniel Odio's Park It DC and Joachim Pfeiffer's TransiCast.

The article discusses the potential of the Web 3.0 Internet technology for use in government services. It defines Web 3.0 as a concept of machine-to-machine communication in the Internet. According to former Minnesota chief information officer (CIO) Gopal Khanna, the Web 3.0 technology will become an important mechanism for the implementation of the government's programs to its citizens. The opinion of the nonprofit organization Code of America's Jennifer Pahlka on the issue is also cited.

The article discusses information technology (IT) models for collaboration among counties and cities in the U.S. that can enhance digital infrastructure amidst the widespread budgetary cuts as of December 2010. These models include the Local Government Information System (LOGIS) in Minnesota, a quasi government agency of which the applications is used for permits and inspection, equipment management and human resources. Pueblo County in Colorado hosts the entire San Luis Valley property assessment management for assessor offices and treasurer's offices.

The article discusses the controversy between local government information technology (IT) departments and IT vendors concerning proposed reduction of vendors' maintenance fees. IT departments want to reduce fees in order to cut costs. Big IT vendors such as SAP and Oracle are reluctant to renegotiate fees citing among others, contractual obligations. A number of local government chief information officers (CIO) have addressed this problem by changing to scaled-down service plans or by transferring to lower-priced vendors.

The article reports that the Sacramento Municipal Utility District (SMUD) in California plans to install 600,000 smart electric meters by December 2011. The project will be funded by 128 million dollars in grants received from the American Recovery and Reinvestment Act (ARRA). SMUD believes that the smart grid system will enable customers to more effectively manage their energy consumption and it will also help the utility deliver power more efficiently. The utility will need to train employees to handle billing questions.

The article focuses on the hybrid approach to consolidation that required city agencies to add basic data to a new enterprise Geographic Information System (GIS). An overview of the situation prior to consolidation is provided along with the solution proposed by Max Samfield, deputy director of the Houston Planning and Development Department in Texas, involving a repository delivered to end-users from a central server farm. Efforts that paved for a 95 to 98 percent accuracy are discussed together with the benefits of the Citrix technology.

The article discusses the problems local U.S. governments face in availing and qualifying for stimulus funds offered by the American Recovery and Reinvestment Act (ARRA). Their lack of manpower combined with the strict conditions for grant qualifications impede their ability to apply for stimulus funding. Some restrictions of broadband grants cited include unserved or underserved coverage requirements for cities or counties, and grants with purposes intended for certain agencies only.

The article addresses some of the security issues associated with the usage of social networking sites in government. Security officials worry that the Web 2.0 tools will expose government networks and sensitive information to dangerous cyber-threats. It details the social networking policy of California and Delaware. It describes how Koobface virus affected social networking site Facebook.

The article tackles the issue of telework in Texas. The Department of Environmental Management (DEM) has teamed up with other agencies to come up with a formal policy on telework practices by 2007. States and government agencies try to expand their telework program to alleviate problems on high price of gasoline, traffic and pollution. Austin started its formal telework policy in 1999 and features a well developed Web portal for telecommuting and better productivity from teleworking employees have been reported.

The article describes how information technology (IT) projects in the U.S. help agencies reduce Medicaid costs. According to most states, inappropriate visits to emergency rooms is the primary factor driving up the costs of Medicaid. Most states understand that early intervention is essential to avoiding grave illnesses that are expensive to treat. In 2000, California made tracking Medicaid fraud a major IT agenda and has appointed Electronic Data Systems to manage the details. INSET: War Against Diabetes.

The article reports on the state and local government projects for environmental concerns in California. The U.S. Environmental Protection Agency (EPA) said data centers consume 1.5 percent of all electricity in the U.S., and they consolidated to reduce their consumption by eliminating unnecessary cooling and processing as well as reducing the floor space. Will Semmes of California Department of General Services (DGS) said California will track how much energy is used and where it is used to comply to the 20 percent cut in energy consumption.

The article offers information on online public education to homeschooled children in grades three to eight through Texas Virtual Academy (TXVA). The TXVA students are required to take the Texas Assessment of Knowledge and Skills (TAKS) exam to verify the minimum performance standards of the enrollees and are provided with computers and boxed materials for the school year. Online sessions are held through Elluminate Live and quizzes are administered through the software QuizStar. A certified educator is available for questions and for online teaching.

The article discusses the benefits of using WiMAX in municipalities in the U.S. It stresses that WiMAX is a better way to produce wireless cloud connectivity to an entire city using a few base stations. WiMAX networks require access points every two square miles for urban areas and one every six square miles for rural areas. It also adds that WiMAX can offer stronger signals and faster service than Wi-Fi. Despite of these benefits, some Wi-MAX critics point to the technology's higher cost

The article focuses on the possible return of the U.S. nuclear power industry in 2007 following its inactivity caused by a series of accidents during the 1970s. Unit 1 Browns Ferry Reactor of Alabama resumed its operation in May 2007 and announced plans to build approximately 30 reactors for Southern states in the next two years. Director of Cato Institute Jerry Taylor is pessimistic about the success of nuclear power plants in satisfying the forthcoming power demand increases in the South.

The article reports on the efforts of U.S. states to generate power from renewable sources. California will require its public utilities to generate 20 percent of their power using renewable energy sources by 2010. New Hampshire and Minnesota have passed the highest renewable energy requirements of public utilities, which is 25 percent by 2025. According to Warren Karlenzing, chief strategy officer of SustainLane, wind and solar are the two main sources of renewable energy sources.

Assessment of dopamine nerve terminal function and integrity is a strategy employed to monitor deficits in Parkinson's disease (PD) patients and in preclinical models of PD. Dopamine replacement therapies effectively replenish the diminished supply of endogenous dopamine and provide symptomatic benefit to patients. Tyrosine hydroxylase (TH), dopamine transporter (DAT), vesicular monoamine transporter 2 (VMAT2), and amino acid decarboxylase (AADC) are widely used markers of dopaminergic neurons and terminals. The present studies were initiated to: (a) assess alterations in all four markers in the MPTP primate model of dopaminergic degeneration and (b) to determine whether L-DOPA treatment may itself modulate the expression of these markers. MPTP treatment induced a significant decline of dopaminergic immunoreactive fiber and terminal density in the basal ganglia. The amount of reduction varied between markers. The rank order of presynaptic marker loss, from most to least profound reduction, was TH > VMAT2 > DAT > AADC. Semiquantitative image analysis of relative dopaminergic presynaptic fiber and terminal density illustrated region-specific reduction of all four markers. Double immunofluorescence colocalization of two presynaptic markers on the same tissue section confirmed there was a more dramatic loss of TH than of VMAT2 or of DAT following MPTP treatment. L-DOPA treatment was associated with a significantly higher level of AADC and VMAT2 immunoreactivity in the caudate nucleus compared to placebo. These results illustrate that neurotoxic injury of the dopamine system in primates leads to altered and differential expression of presynaptic dopaminergic markers in the basal ganglia and that expression of such markers may be modulated by L-DOPA therapy. These findings have implications for the use of biomarkers of disease progression as well as for the assessment of neurorestorative strategies, such as cell replacement, for the treatment of PD.

The article discusses the malfunctions and the vulnerabilities of direct-recording electronic (DRE) voting machines, which was used in the U.S. elections to eliminate paper ballot hazards. Most of the criticism for DRE machines revolves around the lack of a paper trail or tangible documentation. The controversy in Florida's 13th Congressional District brought by voting irregularities is discussed. Mathew Zimmerman of the Electronic Frontier Foundation (EFF) said that electronic voting suffers from a lack of transparency.

Actin filaments play a critical role in the normal physiology of lenticular and retinal cells in the eye. Disruption of the actin cytoskeleton has been associated with retinal pathology and lens cataract formation. Ocular toxicity is an infrequent observation in drug safety studies, yet its impact to the drug development process is significant. Recognizing compounds through screening with a potential ocular safety liability is one way to prioritize development candidates while reducing development attrition. Lens epithelial cells from human, dog, and rat origins and retinal pigmented epithelium cells from human, monkey, and rat origins were cultured and investigated with immunocytochemical techniques. Cells were treated using noncytotoxic doses of the compound, fixed, stained for actin with rhodamine phalloidin, and counterstained for nuclei with TOTO-3, followed by confocal imaging. Tamoxifen and several experimental compounds known to be in vivolens and retinal toxicants caused a reduction in F-actin fluorescence at noncytotoxic concentrations in all cells tested as observed by confocal microscopy. Developing an assay that predicts ocular toxicity helps the development process by prioritizing compounds for further investigation. Drug-induced cytoskeletal alterations may be useful as a potential safety-screening marker of retinal and lens toxicity. The knowledge of actin molecular biology and the application of other mechanistic screens to toxicology are discussed. Reducing this work to a high-throughput platform will enable chemists to select compounds with a reduced risk of ocular toxicity.

The article presents views on offshore outsourcing of government work. Some economists and organizations argue that offshore outsourcing results to an increase in employment in the U.S. Others say that it will promote the rising trend of privatizing government functions which results to better services received by taxpayers. On the other hand, critics say that it will hinder the promotion of citizen employment. Legislators are said to be hindering offshore outsourcing through laws.

The article focuses on information technology project problems in Colorado. The deployment of the Colorado Benefits Management System was established by the Department of Human Services and Department of Health Care policy and Financing to replace several legacy systems with a single integrated program. However, the project failed because benefits were given to those people who did not qualify while some who did qualify did not receive the benefits.

The article focuses on the complaints raised by vendors on the terms of the contract for the 21st Century Project payroll system of the California government. Accenture withdrew its commitment to the project when the state refused to negotiate on warranty requirements. Avanti Advisory president Peter Iannone cites that negotiation on liability requirements for government officials and business executives is difficult.

This article explains that the San Diego County in California will be among the first in the U.S. to switch IT outsourcing partners. With this move by the San Diego County, its current IT provider Computer Sciences Corp. will be replace by Northrop Grumman. The county started outsourcing its IT since 1999. Other local governments in the country that want to successfully out source the first time can get helpful insight from the lessons learned by San Diego County.

Focuses on the transition of broadcasters to digital television in the U.S. Agreement of the U.S. House and Senate to extend broadcasters' digital transmission switchover deadline to February 17, 2009; Recipient of 24 megahertz of spectrum by firefighters, police and other emergency first responders; Views of Ron Haraseth, director of the automated frequency coordination division of APCO International, on the added spectrum for first responders.

Multiple sclerosis is an inflammatory demyelinating disease of the CNS, the aetiology of which is believed to have both genetic and environmental components. We have investigated one of the candidate viruses for the environmental component of multiple sclerosis, the neurotropic human herpesvirus 6 (HHV-6). Utilizing fluorescent in situ hybridization (FISH) techniques, we have examined human post-mortem tissues for the presence of immediate early and late viral gene expression in multiple sclerosis patient normal appearing white matter (NAWM), lesional tissue and normal control brain samples. HHV-6 gene transcription was detected in all tissue samples and was restricted to oligodendrocytes, as determined by double mRNA FISH analysis. Quantitative analysis of viral mRNA expression indicated that both NAWM and lesional multiple sclerosis samples exhibited significantly higher levels of HHV-6 expression compared with the normal control samples. Lesional samples exhibited the highest levels of viral gene expression, with NAWM exhibiting an intermediate level between lesional and control tissues. Immunofluorescence against early and late HHV-6 proteins verified active translation of HHV-6 viral mRNA in oligodendrocytes. Southern blot analysis of nested polymerase chain reactions using extracted genomic DNA and cDNA confirmed the presence of the HHV-6 genome in all individuals, with the active expression profile mirroring the FISH results. The frequent high level of HHV-6 infection in multiple sclerosis samples suggests a possible role in pathogenesis.

The cyclooxygenase isoforms, COX-1 and COX-2, are the rate limiting enzymes in the biosynthesis of prostaglandin E(2), a major prostaglandin involved in epidermal homeostasis and repair. Epidermal injury results in transient hyperplasia and induction of COX-2 expression. The role of COX-2 in this hyperplasia is unknown, however. In this study, we characterized the epidermal expression of COX isozymes following wounding by abrasion in SKH-1 mice using immunohistochemistry, in situ hybridization, and Western analysis. In addition, we evaluated pivotal keratinocyte functions necessary for the reparative hyperplasia, including proliferation by 5-bromo-2'deoxy-uridine labeling and differentiation by the expression of involucrin, keratin 1, and keratin 6. Although COX-1 expression in keratinocytes remained unchanged during wound healing, COX-2 expression was induced coincidentally with keratinocyte proliferation and keratin 6 expression, suggesting a role for COX-2 in epidermal repair. The role of COX-2 was also evaluated using the selective COX-2 inhibitor SC-791 and the traditional COX inhibitors indomethacin and diclofenac. Neither inhibitor altered keratinocyte proliferation or differentiation following abrasion, in contrast to dexamethasone, which delayed these responses. Our results indicated that, although COX-2 expression was coincident with transient epidermal hyperplasia and keratinocyte proliferation/differentiation during the healing of epidermal injury, it does not play a pivotal role in this repair process.

Approximately 3,200 L of water were inoculated with Cryptosporidium oocysts and Giardia cysts. The contaminated water was filtered through a Berkefeld Filter, type TWA 3, as used by the Norwegian army. Nine 10-L samples of filtered water and four 10-L control samples of unfiltered water were analyzed for Cryptosporidium oocysts and Giardia cysts. On average, 1,920 Giardia cysts and 2,735 Cryptosporidium oocysts per 10 L were detected in the unfiltered water. Between 0 and 2 Giardia cysts and between 2 and 47 Cryptosporidium oocysts were detected in the filtered 10-L samples. Percentage removal of parasites was between 99.8 and > 99.95% for Giardia (2.98 to > 3.28 log removal) and between 98.3 and 99.9% (1.76-3.14 log removal) for Cryptosporidium. The Berkefeld filter TWA 3 complies with published recommendations for municipal water supply for removal of Giardia but does not always comply with such regulations for Cryptosporidium.

Gap junction intercellular communication (GJIC) is involved in the regulation of many cellular processes. The gap junction channels are made up of connexins and the flow of polar low molecular weight molecules through these channels is inhibited by several groups of substances, such as tumour promoters and growth factors. The phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA), chlordane and the growth factor epidermal growth factor (EGF) are potent inhibitors of GJIC in several cell types, including the rat liver epithelial cell line IAR6.1. The induced inhibition of communication by TPA and EGF in IAR6.1 cells is associated with hyperphosphorylation of connexin43, the connexin responsible for GJIC. Two enzyme inhibitors, PD98059, a specific inhibitor of MEK kinase, and GF109203X, a selective inhibitor of protein kinase C (PKC), were used to study the signalling pathways involved in the effect of EGF and TPA on GJIC, with the following conclusions. The inhibition of cell communication in IAR6.1 cells by EGF is likely to be mediated by direct phosphorylation of connexin43 by MAP kinase. TPA blocks GJIC mainly by the direct action of PKC, but also partly through cross-talk with the MAP kinase pathway. Connexin43 hyperphosphorylation induced by TPA is, as for EGF, mediated through MAP kinase, while PKC seems to block GJIC either through other substrates or induces a type of connexin43 phosphorylation that causes no significant electrophoresis mobility shift.

The dynamics of dissolved organic matter (DOM) in the Mississippi river plume were investigated during four cruises to the region in 1990–1993. During each cruise, large-volume water samples were collected from a broad salinity gradient (0–36 psu) for the determination of dissolved organic carbon (DOC) concentrations and the isolation of DOM by tangential-flow ultrafiltration. The fraction of DOC recovered by ultrafiltration ranged from 49% in the river to 22% in the Gulf of Mexico. The ultrafiltered DOM (UDOM) was further characterized for the concentrations and compositions of combined neutral sugars and lignin-derived phenols. Concentrations of DOC ranged from 359 μM in the river during the summer to 65 μM in surface waters of the Gulf of Mexico during the winter. Mixing curves indicated minor losses of DOC at low salinities and a major source of DOC at mid salinities. Combined neutral sugars had elevated concentrations at mid salinities where plankton biomass and rates of autotrophic and heterotrophic processes were maximal, indicating that elevated concentrations of sugars and DOC were freshly-derived from plankton. In contrast, concentrations of lignin phenols in UDOM were depleted at low salinities, indicating losses due to flocculation of terrestrially-derived humic substances. The selective removal of syringyl phenols from dissolved lignin was observed in UDOM from higher salinity (>25 psu) waters, providing the first molecular evidence of the removal of terrigenous DOM from the coastal ocean due to photooxidation. Together, these molecular biomarkers indicated much greater dynamic behavior of DOM than was apparent from bulk DOC analyses, and they demonstrated that biological as well as physico-chemical processes were important in controlling the concentrations and compositions of DOM in coastal waters.

To evaluate the clinical outcome of in vitro fertilization (IVF) treatment cycles from individual oocyte donors who underwent multiple sequential donations.

Rates of collagen and non-collagen protein synthesis in rabbit arterial smooth muscle cells (SMC) were determined by using the specific (radio)activity of [3H]proline in the extracellular, intracellular, and prolyl-tRNA pools. The intracellular free proline specific activity was only 25% of the extracellular value in cultures incubated for 12 h in 0.25 mM-proline. The specific activity of prolyl-tRNA was less than 10% of the extracellular specific activity. Increasing the extracellular proline concentration 10-fold (to 2.5 mM), while keeping the extracellular specific activity of proline constant, resulted in equilibration of the specific activities of intracellular and extracellular free proline, but the specific activity of prolyl-tRNA remained at less than 10% of the extracellular specific activity. Therefore, calculated rates of collagen and non-collagen protein synthesis were greatly underestimated using the intracellular or extracellular specific activity of proline. SMC were also incubated with 0.1 mM-[14C]ornithine in 0.25 nM or 2.5 mM non-labelled proline to examine synthesis de novo of proline and prolyl-tRNA from ornithine. In SMC cultures containing 0.25 mM unlabelled proline, the specific activity of intracellular ornithine was approx. 45% of the extracellular specific activity, due to the production of unlabelled ornithine. The specific activity of ornithine-derived intracellular free proline in SMC incubated with 2.5 mM-proline was significantly lower than in SMC incubated in 0.25 mM-proline, due to the influx of unlabelled proline. However, a corresponding difference in the specific activity of [14C]prolyl-tRNA between SMC in 0.25 mM- or 2.5 mM-proline was not observed. Ornithine-derived [14C]proline was incorporated into proteins in a manner different from that of exogenously added radiolabelled proline. A much higher proportion of the proline synthesized de novo was channelled into collagen synthesis relative to total protein synthesis. Together, these results show that intracellular proline pools are highly compartmentalized in arterial SMC. They also suggest that proline synthesized from ornithine may enter a prolyl-tRNA pool separate from that of proline entering from the extracellular medium.

The safety and pharmacokinetics of ofloxacin in 48 healthy male volunteers were studied in a two-center, randomized, double-blind, placebo-controlled study. Ofloxacin (200 or 400 mg) or placebo was administered as 1-h infusions every 12 h for 7 days. Plasma ofloxacin concentrations were measured by high-performance liquid chromatography. Mean harmonic half-lives ranged from 4.28 to 4.98 h in the 200-mg dosing group and from 5.06 to 6.67 h in the 400-mg dosing group. Intragroup comparisons of trough plasma concentration-versus-time data from study days 2 through 7 revealed that steady state was achieved by day 2 of both multiple-dose regimens. Intergroup comparisons of mean harmonic half-lives, the areas under the concentration-time curve from 0 to 12 and 0 to 60 h, clearance, and apparent volume of distribution (area method) revealed that the pharmacokinetics of ofloxacin are dose independent. Both ofloxacin dosage regimens appeared to be reasonably well tolerated. The two dosage regimens of ofloxacin, 200 or 400 mg every 12 h, appear to be safe and provide serum drug concentrations in excess of the MICs for most susceptible pathogens over the entire dosing interval.

The disposition of cefmetazole was studied in 25 subjects with various degrees of renal function after a 1,000-mg, constant-rate, 30-min intravenous infusion of cefmetazole sodium. In six subjects with creatinine clearance (CLCR) of greater than 90 ml/min per 1.73 m2 (group 1), the terminal elimination half-life (t1/2 beta) was 1.31 +/- 0.54 h (mean +/- standard deviation), cefmetazole total body clearance (CLP) was 132.8 +/- 25.1 ml/min per 1.73 m2, and volume of distribution at steady state was 0.165 +/- 0.025 liter/kg. The fraction of dose excreted unchanged in the urine was 84.0% +/- 26.1%. Subjects with CLCRS of 40 to 69 (group 2, n = 6) and 10 to 39 (group 3, n = 6) ml/min per 1.73 m2 demonstrated prolongation of the t1/2 beta (3.62 +/- 1.06 and 5.93 +/- 1.81 h, respectively) and significant reductions in cefmetazole CLP (52.8 +/- 14.3 and 30.2 +/- 10.2 ml/min per 1.73 m2, respectively), compared with group 1. In seven subjects on chronic hemodialysis (group 4) studied during an interdialytic period, the cefmetazole t1/2 beta was increased to 24.10 +/- 8.12 h and the CLP was reduced to 6.8 +/- 2.1 ml/min per 1.73 m2. Cefmetazole CLP correlated positively with CLCR (r = 0.951, P less than 0.001): CLP = (1.181 . CLCR) -- 0.287. The disposition of cefmetazole was also assessed in six group 4 subjects during an intradialytic period. The t1/2 beta during hemodialysis (2.09 +/- 0.69 h) was significantly shorter than that observed during the interdialytic period. The hemodialysis clearance of cefmetazole was 86.1 +/- 20.1 ml/min, and the fraction of cefmetazole removed during hemodialysis was 59.8% +/- 5.9%. It is recommended that patients with renal insufficiency received standard doses of cefmetazole at extended intervals and patients on maintenance hemodialysis received standard doses after hemodialysis.

The disposition of roxithromycin, an investigational macrolide antibiotic, was evaluated in 20 subjects, 10 with normal renal function (creatinine clearance [CLCR] of 116 +/- 17 ml/min [mean +/- standard deviation]) and 10 with severely impaired renal function (CLCR of 10.2 +/- 2.6 ml/min) after a single 300-mg oral dose. Plasma concentration-time data were analyzed in terms of a one- or two-compartment oral absorption model utilizing nonlinear regression analysis. The terminal elimination half-life was significantly prolonged in the group with severely impaired renal function (15.5 +/- 4.7 h) compared with that of the group with normal renal function (7.9 +/- 2.5 h). Apparent total body clearance was significantly reduced in the renally impaired (25.3 +/- 10.5 ml/min) in relation to the group with normal renal function (48.8 +/- 11.1 ml/min). The first-order absorption rate constants and apparent volumes of distribution did not differ between the two groups. These data indicate that the disposition of roxithromycin is significantly delayed in subjects with CLCRs of less than 15 ml/min and suggest that the roxithromycin dosing interval be doubled for these patients.

3,4-Methylenedioxymethamphetamine (MDMA; "ecstasy") is a selective serotonin (5-HT) neurotoxin in animals. There is now preliminary evidence in humans of 5-HT deficits associated with extensive use of MDMA. In order to begin to describe the cognitive and mood effects of chronic MDMA use, nine individuals with extensive MDMA use histories were studied. Despite the absence of memory deficits on clinical examination, a pattern of mild-to-moderate impairment was observed on both the Initial and Delayed Paragraph Tests of the Wechsler Memory Scale; eight of the subjects had at least mild impairment on at least one test in the neuropsychological battery. Despite previously reported suggestive evidence of 5-HT deficit in this group, none reported depressed mood or met clinical criteria for an affective disorder at the time of testing. These preliminary findings raise concern about possible detrimental effects of MDMA use on neuropsychological function for future systematic study and they highlight important issues regarding the effects of 5-HT deficits on cognitive function and mood regulation.

Renin activity appears to be present in low concentrations in the plasma of anephric humans but could be artifactual secondary to inadvertent activation of prorenin during specimen collection and handling or from a renin-like enzyme. We studied the effects of specimen collection, storage, different assay conditions, trypsin activation, and the renin inhibitor EMD 56133 (E Merck, Darmstadt) on plasma renin activity (PRA) in anephric man.PRA was detectable in all seven bilaterally nephrectomized (BNX) patients (0.2 ± 0.1 ng AI/m1/hr, range 0.1 - 0.7) but was significantly lower than normals (2.4 ± 0.3 ng AI/m1/hr, range 1.5 - 3.1, p=0.001). PRA was not different in BNX whether blood samples were collected on ice or at room temperature and assayed immediately or whether samples were frozen and assayed several days later. Prolonged cold storage of samples and five freeze-thaw cycles over six to seven months did not significantly increase PRA in normals or anephrics. However, deliberate repeated freezing and thawing over the period of a single day increased PRA 4.1-fold in BNX and 1.6-fold in normals. Renin-like activity was also detected in BNX individuals using renin concentration determinations with either excess human or sheep angiotensinogen. The inhibition of renin activity (IC-50% - 3.16 × 10-9 molar) by EMD 56133 was not different between BNX and normals.Thus, active renin is present in the plasma of anephric humans and does not result from the inadvertent activation of prorenin due to sample handling. Although the source of PRA in BNX is unknown, the enzyme appears functionally normal as evidenced by the dose-response to a single renin inhibitor.

A synthetic amphiphilic polymer, poly(2-ethylacrylic acid), induces pore formation in artificial phospholipid bilayers under mildly acidic conditions. This process is pH-controllable and produces cation-selective ion channels of at least three unique large conductances with differing Na⁺/Cl^- permeability ratio values. Two general types of channel gating kinetics are observed, one flickering and irregular and one regular and discrete. The discrete channel activity resembles that of well-characterized biological and synthetic peptides. Given the heterogeneity of polymer structure and conformation, this observation raises questions about the mechanism of polymer channel formation and the nature of these channels in lipid bilayer membranes.

We examined the effects of enclomiphene and zuclomiphene, alone and in combination with oestradiol, on basal and gonadotrophin-stimulated progesterone secretion by isolated subpopulations of both large (granulosa-lutein) and small (theca-lutein) ovine luteal cells. Isolated large and small luteal cells derived from intact, enucleated ovine corpora lutea were incubated for 48-120 h with or without 22R-hydroxycholesterol or pregnenolone (2.5 microM) and a range of enclomiphene, zuclomiphene, and/or oestradiol concentrations (3-100 microM), both with and without ovine luteinizing hormone (100 ng/ml). Spent media were assayed in duplicate for progesterone content by radioimmunoassay. Enclomiphene, zuclomiphene, and oestradiol exhibited equivalent dose-dependent inhibitory effects on basal and gonadotrophin-stimulated small and large ovine luteal cell progesterone secretion under all substrate conditions. Both cell types became more sensitive to clomiphene inhibition with increasing time in culture. In combined treatments, the effects of oestradiol and either enclomiphene or zuclomiphene became additive in longer-term cultures and were never antagonistic. In this model system, (i) clomiphene, like oestradiol, appears to inhibit 3beta-hydroxysteroid dehydrogenase activity, (ii) both stereoisomers act as oestrogen agonists, (iii) neither demonstrates any anti-oestrogenic properties, and (iv) both large and small luteal cells become more sensitive to clomiphene inhibition with increasing duration of exposure.

This study evaluated the impact of age and ovarian reserve status on cumulative pregnancy rates. Approximately 1200 women from a general infertile population underwent ovarian reserve screening with the clomiphene citrate challenge test in the first few months of their initial evaluation. All patients then underwent a thorough infertility evaluation with therapy appropriate for their specific diagnoses. Patients with evidence of tubal disease, peritoneal adhesive disease, or male factor were eliminated. The 588 remaining patients were evaluated based on their age and ovarian reserve status, and their long-term pregnancy rates were compared using life table analyses. There was a dramatic decrease in pregnancy rates associated with an abnormal clomiphene citrate challenge test which was uniformly poor independent of age. Patients with normal ovarian reserve had much higher pregnancy rates, but a significant age-related decline in pregnancy rates was clearly identified. We conclude that women with evidence of diminished ovarian reserve have uniformly poor pregnancy rates independent of their age, but that age remains an important prognostic factor among those with a normal ovarian reserve. The combined use of maternal age and ovarian reserve screening should be used when counselling individual patients regarding their long-term prognoses for conception.

Active renin is a heterogeneous enzyme that can be separated into multiple forms with high-resolution isoelectric focusing. The isoelectric heterogeneity may result from differences in glycosylation between the different forms. In order to determine the relationship between active renin heterogeneity and differences in composition or attachment of oligosaccharides, two separate experiments were performed: (i) Tunicamycin, which interferes with normal glycosylation processing, increased the proportion of relatively basic renin forms secreted into the incubation media by rat renal cortical slices, (ii) Endoglycosidase F, which enzymatically removes carbohydrate from some classes of glycoprotein, similarly increased the proportion of relatively basic forms when incubated with active human recombinant renin. In addition, further studies with inhibitors of human renin activity revealed that the heterogeneous renin forms were similarly inhibited by two separate renin inhibitors. These results are consistent with the hypothesis that renin isoelectric heterogeneity is due in part to differences in carbohydrate moiety attachment and that the heterogeneity of renin does not influence access of direct renin inhibitors to the active site of renin.

It has previously been described that perifusion of acutely dispersed adenohypophyseal cells with hypotonic medium causes an immediate high-amplitude “on” burst of luteinizing hormone (LH) secretion. In the present report the converse study with hyperosmolar solutions has been made. Perifusion with hypertonic medium depressed LH secretion; return to isotonicity caused an immediate high-amplitude “off” burst of LH secretion closely resembling that induced by hypotonic perifusion. The data give further support to the theory that exocytotic secretion may involve expansion of the outer cell membrane, thus drawing secretory granules to the cell surface where their contents are extruded.

The disposition of famotidine was evaluated in 18 patients; Group 1, mild renal insufficiency, [creatinine clearance (CLCR): 30–60 mL/min]; Group 2, moderate to severe renal insufficiency (CLCR: 10–30 mL/min); Group 3, end‐stage renal disease requiring maintenance hemodialysis (anuric). Blood and urine samples were obtained over a 72‐hour period. Plasma concentration‐time data demonstrated biexponential decay. The terminal elimination half‐life was prolonged in Group 3 (18.6 ± 5.7 hr) compared with Groups 1 (9.3 ± 2.3 hr) and 2 (9.7 ± 1.7 hr), P< .05. Steady‐state volume of distribution ranged from 0.80 to 1.26 L/kg but did not differ among the groups. Total body clearance (CLP) and renal clearance were significantly lower in Groups 2 and 3 patients compared with Group 1 patients. Nonrenal clearance was not related to CLCR. The CLPcorrelated well with CLCR(CLP= 1.59 CLCR+ 33.8, r = 0.830, P< .05). These data indicate that dosage adjustment may be necessary in patients who have renal insufficiency.

Epoetin may enhance autologous blood donation, but efficacy and dose response have not been established. This multicenter, double-blind trial compared intravenous placebo (n = 23) with epoetin beta, 250 U/kg (n = 23), 500 U/kg (n = 19), and 1000 U/kg (n = 22), administered three times weekly for 26 days. Normal men (age, 28 ± 7 years; mean ± SD) received phlebotomies up to three times weekly as long as the hemoglobin remained ≥12 gm/dl. Subjects treated with epoetin donated 32% more units of blood (p < 0.05) compared with placebo. A dose response was not observed. Platelet counts increased with epoetin compared with placebo, but platelet function and bleeding time did not change. Prothrombin times increased and partial thromboplastin times decreased with both epoetin and placebo. The supernatant of packed red blood cells collected after multiple phlebotomies and stored 42 days had slightly lower glucose concentrations and pH after therapy with epoetin. Blood pressure did not change with epoetin or placebo. These findings support the efficacy and safety of epoetin for enhancing the erythropoietic response of normal subjects during intensive phlebotomy.Clinical Pharmacology and Therapeutics (1992) 52, 205–213; doi:10.1038/clpt.1992.131