Miracle-dz/UniFAR-FTUs huggingface dataset:
Intracellular Indinavir Pharmacokinetics in HIV-Infected Patients: Comparison with Plasma Pharmacokinetics

Objective To determine intracellular concentrations of indinavir (IDV) and investigate the relationship between plasma and intracellular IDV pharmacokinetics in HIV-infected patients. Methods A pharmacokinetic study of 10 patients receiving IDV plus dual nucleoside analogue therapy. Peripheral blood mononuclear cells were isolated by density gradient centrifugation and cell counts estimated. IDV was extracted from cells in the presence of 60% methanol and evaporated to dryness. Both plasma and intracellular IDV samples were assayed by high performance liquid chromatography linked to mass spectrometry. Data were subjected to non-compartmental pharmacokinetic analysis. Results The mean intracellular IDV area under the curve over 8 h (AUC0-8) was lower than the plasma AUC0-8 (7574 ±1003 vs 25060 ±4171 ng/ml/h; P<0.004). However, both the elimination half-life (t1/2) and the mean residence time (MRT) of IDV intracellularly were prolonged compared with plasma (t1/2: 2.0 ±0.3 vs 1.2 ±0.09 h; MRT: 3.6 ±0.6 vs 2.1 ±0.1 h; P<0.05). All patients were responsive to therapy at the time of the study, as assessed by HIV plasma RNA levels. Individual plasma versus intracellular time course results suggest that, due to the prolonged intracellular half-life, some patients may achieve acceptable intracellular IDV concentrations despite sub-therapeutic plasma levels. Similarly, potentially inadequate intracellular concentrations may occur despite therapeutic plasma concentrations. Conclusions There is no significant intracellular accumulation of IDV within the lymphocytes of HIV-1-infected patients relative to plasma. However, intracellular concentrations are compatible with reported IDV-free drug concentrations in plasma. The intracellular elimination half-life and mean residence time of IDV are significantly prolonged compared with plasma. This may in part explain why certain patients maintain adequate viral suppression despite sub-therapeutic plasma IDV levels.
Familial cancer risks in offspring from discordant parental cancers

Analysis of familial cancer risks between discordant sites provides etiologic understanding on genetic and environmental risks factors of site‐specific cancers. We used the Swedish nation‐wide Family‐Cancer Database to analyze familial risks in discordant cancers of offspring and parents. Familial risk ratios (FRRs) were calculated for cancer in offspring aged 15 to 53 years at 22 sites, discordant from parental sites. We confirmed many reported associations. Consistent novel findings associated parental‐offspring sites of pancreas‐breast, breast‐testis and uterus‐nervous system. For these, the FRRs were modest, 1.2 to 1.5 in the whole Database, but the FRRs increased in those whose parents were diagnosed before age 50. Pancreas and liver cancers showed FRRs of 2.5 to 3.3 in offspring of women and of 1.3 in offspring of men. One or both of these cancers was/were associated with cancers of stomach, colon, breast, uterus, ovary and prostate. Melanoma was associated with pancreas, breast, skin and nervous‐system cancers and with leukemias. Myeloma showed a concordant FRR of about 4.0 and was associated with prostate cancer and non‐thyroid endocrine‐gland cancers. Mutations in known cancer‐related genes may explain some of these findings, but new susceptibility genes are yet to be found. For melanoma, pancreatic and liver cancer, environmental factors are important etiologic factors and may contribute to the familial effects observed. Int. J. Cancer 81:12–19, 1999. © 1999 Wiley‐Liss, Inc.
Upper Airway Resistance Syndrome

The term ‘upper airway resistance syndrome’ denotes an entity characterized by the presence of daytime fatigue or sleepiness in the presence of a normal respiratory disturbance index and oxygen saturation. Despite some similarities, certain specific clinical and diagnostic features distinguish it from the obstructive sleep apnea syndrome. The essence of diagnosis lies in the documentation of increasing esophageal pressures during sleep with associated transient EEG arousals. Furthermore, the evidence suggests an abnormal blood pressure response to the changes in esophageal pressures and arousals. The exact pathophysiology is currently unclear. Continuous positive airway pressure is an effective mode of therapy, although the low compliance rate limits its use. The role of radiofrequency ablation of the palatal tissues, other surgical procedures, and oral appliances in the treatment of upper airway resistance syndrome need to be investigated more rigorously.
Nuclear Envelope Breakdown Can Substitute for Primary Envelopment-Mediated Nuclear Egress of Herpesviruses

ABSTRACT Herpesvirus nucleocapsids assemble in the nucleus but mature to infectious virions in the cytoplasm. To gain access to this cellular compartment, nucleocapsids are translocated to the cytoplasm by primary envelopment at the inner nuclear membrane and subsequent fusion of the primary envelope with the outer nuclear membrane. The conserved viral pUL34 and pUL31 proteins play a crucial role in this process. In their absence, viral replication is strongly impaired but not totally abolished. We used the residual infectivity of a pUL34-deleted mutant of the alphaherpesvirus pseudorabies virus (PrV) for reversion analysis. To this end, PrV-ΔUL34 was serially passaged in rabbit kidney cells until final titers of the mutant virus PrV-ΔUL34Pass were comparable to those of wild-type PrV. PrV-ΔUL34Pass produced infectious progeny independently of the pUL34/pUL31 nuclear egress complex and the pUS3 protein kinase. Ultrastructural analyses demonstrated that this effect was due to virus-induced disintegration of the nuclear envelope, thereby releasing immature and mature capsids into the cytosol for secondary envelopment. Our data indicate that nuclear egress primarily serves to transfer capsids through the intact nuclear envelope. Immature and mature intranuclear capsids are competent for further virion maturation once they reach the cytoplasm. However, nuclear egress exhibits a strong bias for nucleocapsids, thereby also functioning as a quality control checkpoint which is abolished by herpesvirus-induced nuclear envelope breakdown.
NMR Imaging of Fluid Exchange between Macropores and Matrix in Eogenetic Karst

Sequential time‐step images acquired using nuclear magnetic resonance (NMR) show the displacement of deuterated water (D2O) by fresh water within two limestone samples characterized by a porous and permeable limestone matrix of peloids and ooids. These samples were selected because they have a macropore system representative of some parts of the eogenetic karst limestone of the Biscayne Aquifer in southeastern Florida. The macroporosity, created by the trace fossil Ophiomorpha, is principally well connected and of centimeter scale. These macropores occur in broadly continuous stratiform zones that create preferential flow layers within the hydrogeologic units of the Biscayne. This arrangement of porosity is important because in coastal areas, it could produce a preferential pathway for salt water intrusion. Two experiments were conducted in which samples saturated with D2O were placed in acrylic chambers filled with fresh water and examined with NMR. Results reveal a substantial flux of fresh water into the matrix porosity with a simultaneous loss of D2O. Specifically, we measured rates upward of 0.001 mL/h/g of sample in static conditions, and perhaps as great as 0.07 mL/h/g of sample when fresh water continuously flows past a sample at velocities less than those found within stressed areas of the Biscayne. These experiments illustrate how fresh water and D2O, with different chemical properties, migrate within one type of matrix porosity found in the Biscayne. Furthermore, these experiments are a comparative exercise in the displacement of sea water by fresh water in the matrix of a coastal, karst aquifer since D2O has a greater density than fresh water.
Photonic Generation of Frequency-Quadrupled Microwave Signal With Tunable Phase Shift

A photonic scheme for frequency-quadrupled microwave signal generation with full 360 ° arbitrarily tunable phase shift is proposed and experimentally demonstrated. Two coherent optical components are generated by biasing a Mach-Zehnder modulator at maximum transmission point to suppress odd-order sidebands. Then, two second order sidebands together with the optical carrier are sent to a programmable filter to reject the optical carrier and introduce a phase shift to one of the second order sidebands. A frequency-quadrupled microwave signal with tunable phase is finally obtained by beating the two sidebands at a photodetector. Tunable phase shift of full 360 ° with a microwave frequency from 30 to 42.4 GHz is experimentally demonstrated. The proposed approach has potential applications in the broadband array signal processing system.
Quantification of surface EMG signals to monitor the effect of a Botox treatment in six healthy ponies and two horses with stringhalt: preliminary study.

REASONS FOR PERFORMING THE STUDY Therapeutic options for stringhalt in horses are limited, whereas medical experiences with botulinum toxin type A (Botox) have been positive. To evaluate its effectiveness in horses, surface electromyography (sEMG) signals before and after injection need to be quantified. HYPOTHESIS Treatment of healthy ponies and cases with Botox should reduce muscle activity in injected muscles and reduce spastic movements without adverse side effects. METHODS Unilaterally, the extensor digitorum longus, extensor digitorum lateralis and lateral vastus muscles of 6 healthy mature Shetland ponies and 2 talented Dutch Warmblood dressage horses with stringhalt were injected (maximum of 400 iu per pony and 700 iu per case; 100 iu in 5 ml NaCl divided into 5 injections) with Botox under needle EMG guidance. Surface EMG data were evaluated using customised software, and in the individuals gait was analysed using Proreflex. Statistical analysis was performed using mixed models and independent sample t test (P < 0.05). RESULTS Surface EMG signals were quantified using customised software. The area under the curve (integrated EMG) in time was used as variable. It became significantly reduced in injected muscles after injection of Botox in normal ponies (P < 0.05). This effect was present from Day 1 until Day 84 after injection. In the 2 cases, after injection of 3 muscles, the integrated EMG in time became significantly reduced in all 3 muscles. Kinematic measurements confirmed reduction of frequency and amplitude of hyperflexing or hyperabducting strides of the affected hindlimbs. The duration of effect was also seen in the cases until around 12 weeks after injection. CONCLUSIONS AND POTENTIAL RELEVANCE After EMG guided injections of Botox, sEMG signals recorded from injected muscle were reduced, which proves this to be a useful tool in statistically evaluating a treatment effect. The positive results of this pilot study encourage further research with a larger group of clinical cases.
Evidence for agonist-induced interaction of angiotensin receptor with a guanine nucleotide-binding protein in bovine adrenal zona glomerulosa.

Previous studies have documented that high affinity binding of [125I]angiotensin II to adrenal cortex receptors was modulated by guanine nucleotides. Since in other receptor systems, similar properties of hormone-receptor interactions were shown to be specific for agonists, we studied the differential binding characteristics of agonists and antagonists to this receptor using a new radiolabeled antagonist [125I] [Sar1,Ile8] angiotensin II. Receptor saturation studies indicate that the antagonist is binding to a homogeneous population of sites with a Kd of 0.6-2.0 nM and with a receptor density around 1 pmol/mg of protein. Competition curves using unlabeled antagonists are characterized by a slope factor of 1 and a single Kd of 1-3 nM. Addition of guanylylimidodiphosphate to the assay is absolutely without effect on radiolabeled antagonist binding. In contrast, competition curves using the full agonists angiotensin II, [Sar1]angiotensin II, angiotensin III, and [des-Arg]angiotensin III display slope factors of 0.79, 0.87, 0.70, and 0.84, respectively. These curves can be explained by two apparent forms of the receptor having high and low affinity for the agonist. The higher affinity form associated with these four agonists is characterized by a Kd of 1.2 nM, 0.25 nM, 0.8 nM, and 3 microM, and corresponds to 60, 56, 42, and 25% of angiotensin II-binding sites, respectively. The other form displays 13- to 33-fold lower affinity. Addition of guanine nucleotide to the assay results in a 2-4-fold shift to the right and a steepening (slope factor 0.9-1.0) of agonist competition curves. Angiotensin II receptors, occupied by the full agonist [131I] [Sar1] angiotensin II or by the antagonist [125I] [Sar1, Ile8]angiotensin II, were then solubilized with the nonionic detergent octylglucoside. Dissociation of the agonist [131I] [Sar1] angiotensin II from solubilized receptors is enhanced by guanylylimidodiphosphate or sodium acetate, while dissociation of the antagonist [125I] [Sar1, Ile8]angiotensin II displays little sensitivity towards guanine nucleotides or increased ionic strength. Inclusion of bile salts in the solubilization medium preferentially destabilizes receptor-bound agonist, presumably by interfering with protein-protein interactions required for high affinity agonist binding. Separation of radiolabeled agonist and antagonist-occupied solubilized receptor complexes by steric exclusion high performance liquid chromatography reveals that the agonist-occupied receptor complex behaves as a larger protein than the antagonist-occupied receptor complex. (ABSTRACT TRUNCATED AT 400 WORDS)
The potentials for corporatization of public hospitals: The case of Egypt

APA Citation Abdelaleem, M. (2017). The potentials for corporatization of public hospitals: The case of Egypt [Master’s thesis, the American University in Cairo]. AUC Knowledge Fountain. https://fount.aucegypt. edu/etds/175 MLA Citation Abdelaleem, Mohamed Fayek. The potentials for corporatization of public hospitals: The case of Egypt. 2017. American University in Cairo, Master's thesis. AUC Knowledge Fountain. https://fount.aucegypt. edu/etds/175
Tissue Factor Is Rapidly Elevated in Plasma Collected from the Pericardial Cavity during Cardiopulmonary Bypass

Summary There is growing evidence that the tissue factor/factor VIIa pathway of coagulation is enhanced during cardiopulmonary bypass. Hitherto, available evidence has suggested that upregulated monocyte bound tissue factor is made available, either in the blood collected from the site of surgery or on circulating cells. However, cellular upregulation is slow, while generation of factor VIIa in blood collected from the pericardial cavity is rapid. We have therefore investigated the possibility of an alternative source of tissue factor, plasma (as opposed to cellular) tissue factor in blood samples taken from the central vein catheter (systemic circulation) and collected from the pericardial cavity during cardiopulmonary bypass. Six patients undergoing first time cardiopulmonary bypass grafting were studied. Tissue factor antigen was found to be rapidly elevated (by 15 min) in the pericardial plasma, ∼5-fold above systemic levels (p <0.004). Similar elevations were found in markers of coagulation activation, factor VIIa antigen (p = 0.066), prothrombin fragment F1+2 (p <0.003) and thrombin-antithrombin complex (p <0.03). To explore whether plasma tissue factor was (or had been) functionally active, factor VIIa was measured also with the soluble tissue factor functional assay after removal of heparin. Functional factor VIIa activity fell significantly in the systemic circulation, probably due to the heparin-induced increase (∼15-fold) in tissue factor pathway inhibitor (TFPI), but was elevated in pericardial blood compared with that taken from the central line catheter (p <0.006). These results demonstrate that both components of the activation complex for the extrinsic pathway of coagulation are rapidly generated in pericardial blood during bypass.
Oral Activity of a Methylenecyclopropane Analog, Cyclopropavir, in Animal Models for Cytomegalovirus Infections

ABSTRACT We reported previously that purine 2-(hydroxymethyl)methylenecyclopropane analogs have good activity against cytomegalovirus infection. A second-generation analog, (Z)-9-{[2,2-bis-(hydroxymethyl)cyclopropylidene]methyl}guanine (ZSM-I-62, cyclopropavir [CPV]), has particularly good activity against murine and human cytomegaloviruses (MCMV and HCMV) in vitro. To determine the oral activity of this compound in vivo, BALB/c or severe combined immunodeficient (SCID) mice infected with MCMV and two models using SCID mice implanted with human fetal tissue and subsequently infected with HCMV were used. In MCMV-infected normal mice, CPV at 10 mg/kg of body weight was highly effective in preventing mortality when administered at 24, 48, or 72 h post-viral inoculation and reduced titers of virus in tissues of SCID mice by 2 to 5 log10. In one HCMV model, human fetal retinal tissue was implanted into the anterior chamber of the mouse eye and inoculated with the Toledo strain of HCMV, and in the second, human fetal thymus and liver tissues were implanted under the kidney capsule of mice and then inoculated with HCMV. In general, replication of HCMV in both types of implant tissue increased from 7 through 21 to 28 days and then gradually decreased to undetectable levels by 8 weeks postinfection. Oral treatment with 45 or 15 mg of CPV/kg initiated 24 h after infection was highly effective in reducing replication to undetectable levels in both models and was generally more effective than ganciclovir. These data indicate that the methylenecyclopropane analog, CPV, was highly efficacious in these four animal models and should be evaluated for use in HCMV infections in humans.
Biosynthesis of the Sesquiterpene Antibiotic Albaflavenone in Streptomyces coelicolor A3(2)*

Cytochrome P450 170A1 (CYP170A1) is encoded by the sco5223 gene of the Gram-positive, soil-dwelling bacterium Streptomyces coelicolor A3(2) as part of a two-gene cluster with the sco5222 gene. The SCO5222 protein is a sesquiterpene synthase that catalyzes the cyclization of farnesyl diphosphate to the novel tricyclic hydrocarbon, epi-isozizaene (Lin, X., Hopson, R., and Cane, D. E. (2006) J. Am. Chem. Soc. 128, 6022–6023). The presence of CYP170A1 (sco5223) suggested that epiisozizaene might be further oxidized by the transcriptionally coupled P450. We have now established that purified CYP170A1 carries out two sequential allylic oxidations to convert epi-isozizaene to an epimeric mixture of albaflavenols and thence to the sesquiterpene antibiotic albaflavenone. Gas chromatography/mass spectrometry analysis of S. coelicolor culture extracts established the presence of albaflavenone in the wild-type strain, along with its precursors epi-isozizaene and the albaflavenols. Disruption of the CYP170A1 gene abolished biosynthesis of both albaflavenone and the albaflavenols, but not epi-isozizaene. The combined results establish for the first time the presence of albaflavenone in S. coelicolor and clearly demonstrate that the biosynthesis of this antibiotic involves the coupled action of epi-isozizaene synthase and CYP170A1.
I Say a Little Prayer for You Do Prayers Matter in Marriage and Family Life ?

Comp. by: <USER> Date: 03 Jul 2013 Time: 08:59:09 PM Stage: <STAGE> Page Number: 341 Contemporary Issues in Family Studies: Global Perspectives on Partnerships, Parenting and Support in a Changing World, First Edition. Edited by Angela Abela and Janet Walker. © 2013 John Wiley & Sons, Ltd. Published 2013 by John Wiley & Sons, Ltd. I Say a Little Prayer for You Do Prayers Matter in Marriage and Family Life?
Immediate Effect of Static and Proprioceptive Neuromuscular Facilitation Stretching on Hip Adductor Flexibility in Female Ballet Dancers

The aim of the present study was to investigate the immediate effects of static and proprioceptive neuromuscular facilitation (PNF) stretching on the flexibility of hip adductors in female ballet dancers. Forty-five subjects (age: 28.5 ± 8.0 years; minimum two years of ballet training) were randomly assigned to three groups: PNF (contract-release technique), Static, and Control. Subjects in the PNF and Static groups performed four sets of 30 second stretching with an interval of 30 seconds between sets. The control group stayed at rest for the same time spent by the PNF and Static groups during the stretching sessions. Maximal range of motion was measured before and immediately after the experimental and control protocols in all groups. The results indicated significant differences between pre- and post-stretching flexibility in both PNF and Static groups (p < 0.0001; effect size = 0.24 and 0.39, respectively), whereas no change was identified in the Control group (p = 0.265). However, no differences in post-exercise flexibility were found between PNF and Static groups (p = 0.235). It is concluded that static and PNF stretching methods provoked similar post-exercise acute effects on the maximal range of motion of hip adductors in highly flexible female ballet dancers.
Incorporation of Acute Dynamic Ventilation Changes into a Standardized Physiologically Based Pharmacokinetic Model

A seven-compartment physiologically based pharmacokinetic (PBPK) model incorporating a dynamic ventilation response has been developed to predict normalized internal dose from inhalation exposure to a large range of volatile gases. The model uses a common set of physiologic parameters, including standardized ventilation rates and cardiac outputs for rat and human. This standardized model is validated against experimentally measured blood and tissue concentrations for 21 gases. For each of these gases, body-mass-normalized critical internal dose (blood concentration) is established, as calculated using exposure concentration and time duration specified by the lowest observed adverse effect level (LOAEL) or the acute exposure guideline level (AEGL). The dynamic ventilation changes are obtained by combining the standardized PBPK model with the Toxic Gas Assessment Software 2.0 (TGAS-2), a validated acute ventilation response model. The combined TGAS-2P model provides a coupled, transient ventilation and pharmacokinetic response that predicts body mass normalized internal dose that is correlated with deleterious outcomes. The importance of ventilation in pharmacokinetics is illustrated in a simulation of the introduction of Halon 1301 into an environment of fire gases.
Secondary Traumatic Stress in Trauma Nurses: Prevalence and Exposure, Coping, and Personal/Environmental Characteristics

The purpose of this study is to determine the incidence of secondary traumatic stress (STS) in nurses who primarily care for trauma patients. A demographic/behavioral survey and Penn Inventory to measure the presence of STS were distributed to 262 nurses in a level I trauma center. Relationships between STS and years of experience, coping strategies, and personal and environmental characteristics were examined. Response rate was 49%. The median Penn Inventory score was 17.5. Nine nurses (7%) scored 35 or more, reflecting STS. Those with STS had fewer years of nursing experience and in trauma nursing, were more likely to use medicinals, and had fewer and weaker support systems.