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Advanced ovarian cancer with peritoneal metastasis is challenging to treat. Limited tumor delivery and penetration of the therapeutics to deep tumor regions are significant barriers to effective treatment. The rising radiopharmaceuticals offer hopes for patients through targeted delivery. However, site specific delivery avoiding off target effect remain critical and challenging. We have developed radioactive 166 Holmium loaded mesoporous silica nanoparticles ( 166 Ho-MSNs) that exhibited predominant accumulation to peritoneal metastases of ovarian cancer upon intraperitoneal administration. It was observed that fluorescence labeled radioactive 166 Ho-MSNs distributed throughout the tumor tissues, while non-radioactive fluorescent 165 Ho-MSNs showed mainly tumor surface deposition of MSNs. The deep penetration leads to uniform therapeutic radiation distribution and absorbed doses within tumors as demonstrated by the dosimetry analysis. The radiation dosing regimen consisting of two 100 µCi 166 Ho-MSN doses separated by 7 days decreased tumor activity and increased the overall lifespan and ascites free survival in several models of IP tumor-bearing mice. These findings illustrate that 166 Ho-MSN is promising for the treatment of ovarian peritoneal metastasis, with selective targeting advantage of the nanoparticles and limited off-target radiation exposure., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Xiuling Lu reports financial support was provided by Nami Therapeutics Corporation. Xiuling Lu reports financial support was provided by National Cancer Institute. Xiuling Lu reports financial support was provided by American Cancer Society. Xiuling Lu reports a relationship with Nami Therapeutics Corporation that includes: equity or stocks. Xiuling Lu has patent issued to Nami Therapeutics Corporation. X.Lu is serving on the editorial board of International Journal of Pharmaceutics If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.]., (Copyright © 2024 Elsevier B.V. All rights reserved.)

In situ forming implants (ISFIs) composed of biodegradable polymers and biocompatible solvents are generally designed for sustained drug release. In this study, a non-invasive computed tomography (CT) imaging approach is used to achieve real time imaging of ISFIs in vivo and in vitro using leuprolide acetate in situ forming implant as a model drug product. The process of implant formation, inner structure change and their impact on drug release were elucidated. Real-time drug distribution was unveiled by the CT contrast agent, iohexol, where it shows a core-shell structure of the deposition. The incorporation of leuprolide acetate (LA) led to a reduced extent of burst release, prolongated release profile, and extended implant size expansion. LA was found to interact with the solvent and slowed down the polymer phase inversion, thus significantly changed the drug distribution in the implant and reduced the drug release. The implant inner structure identified through SEM, implant size change, and polymer degradation along with the CT real time imaging all consistently support the implant formation differences and their implant on the drug release. Similar patterns of implant size expansion and iohexol distribution in the implants were observed both in vitro and in vivo for the implants with and without LA. The comprehensive understanding of the impact of implant formation on drug release through real time CT imaging facilitates the ISFI product development and evaluation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Inertial confinement fusion experiments taking place at the National Ignition Facility are generating ever increasing amounts of fusion energy, with the deuterium tritium fusion neutron yield growing a hundredfold over the past ten years. Strategies must be developed to mitigate this harsh environment's deleterious effects on the operation and the performance of the time-resolved x-ray imagers deployed in the National Ignition Facility target bay to record the dynamics of the implosions. We review the evolution of these imagers in recent years and detail some of the past and present efforts undertaken to maintain or improve the quality of the experimental data collected on high neutron yield experiments. These include the use of a dump-and-read electronic backend, the selection of photographic film with a low background sensitivity, and the optical filtering of Cherenkov radiation., (© 2024 Author(s). Published under an exclusive license by AIP Publishing.)

We previously reported that hydroxylated oxime ether lipids (OELs) efficiently deliver functional Dicer substrate siRNAs (DsiRNAs) in cells. Here, we explored in vivo utility of these OELs, using OEL4 as a prototype and report that surface modification of the OEL4 formulations was essential for their in vivo applications. These surface-modified OEL4 formulations were developed by inclusion of various PEGylated lipids. The vesicle stability and gene knock-down were dependent on the PEG chain length. OEL4 containing DSPE-PEG350 and DSPE-PEG1000 (surprisingly not DSPE2000) promoted gene silencing in cells. In vivo studies demonstrated that OEL4 vesicles formulated using 3 mol% DSPE-PEG350 accumulate in human lung cancer (A549-luc2) xenografts in mice and exhibit a significant increase in tumor to liver ratios. These vesicles also showed a statistically significant reduction of luciferase signal in tumors compared to untreated mice. Taken together, the scalable OEL4:DSPE-PEG350 formulation serves as a novel candidate for delivery of RNAi therapeutics., (Published by Elsevier Inc.)

The neuropeptide calcitonin gene-related peptide (CGRP) is known to play a central role in the underlying pathophysiology of migraine. In comparison to the effective triptan class of antimigraine treatments, the CGRP antagonists possess a comparable efficacy but a superior cardiovascular safety profile in patients. This paper describes the development of selective and potent peptidic CGRP antagonist, FE 205030, that has a fast onset of action and an optimal half-life (subcutaneous T max ~ 60 min, and t 1/2 ~ 4.4 h in 80 kg pigs, respectively), which is key to prevention of the progression of debilitating migraine symptoms. The in vivo efficacy of this agent has been established a translational pharmacodynamic model (inhibition of capsaicin-induced increase in skin blood flow) in cynomolgus monkeys and shows maximal inhibitory activity at circulating concentrations of 30-100 nM. Antagonist activity of FE 205030 was characterized on CGRP-induced vasodilation in isolated human mesenteric resistance arteries in an ex vivo isometric myograph study, and FE 205030 effectively blocked CGRP-induced vasodilation with a pA 2 of 9.3 ± 0.1, mean ± standard error. Multispecies allometric scaling and modeling of subcutaneous (SC) effective concentrations indicates that a dose of 10-30 mg/day is sufficient to achieve a drug exposure/target coverage of 8h, which is useful to prevent migraine recurrence in patients. The molecule also possesses appropriate physicochemical properties that allows for a convenient dosing form factor of 1 ml injection volume with a sufficient solubility and acceptable short-term stability, optimal for treatment of acute migraine episodes in patients. Hence, FE 205030 may provide an important fast-acting injectable option for patients suffering from frequent acute migraine episodes, complementary to preventative monoclonal antibodies and oral small molecule CGRP-R antagonist therapies., (Copyright © 2021 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.)

Our understanding of the aetiology and pathophysiology of endometriosis remains limited. Disease modelling in the field is problematic as many versions of induced mouse models of endometriosis exist. We integrated bioluminescent imaging of 'lesions' generated using luciferase-expressing donor mice. We compared longitudinal bioluminescence and histology of lesions, sensory behaviour of mice with induced endometriosis and the impact of the gonadotropin-releasing hormone antagonist Cetrorelix on lesion regression and sensory behaviour. Four models of endometriosis were tested. We found that the nature of the donor uterine material was a key determinant of how chronic the lesions were, as well as their cellular composition. The severity of pain-like behaviour also varied across models. Although Cetrorelix significantly reduced lesion bioluminescence in all models, it had varying impacts on pain-like behaviour. Collectively, our results demonstrate key differences in the progression of the 'disease' across different mouse models of endometriosis. We propose that validation and testing in multiple models, each of which may be representative of the different subtypes/heterogeneity observed in women, should become a standard approach to discovery science in the field of endometriosis., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2021. Published by The Company of Biologists Ltd.)

The use of intraperitoneal administration of nanoparticles has been reported to facilitate higher concentrations of nanoparticles in metastatic peritoneal tumors. While this strategy is appealing for limiting systemic exposure of nanocarrier delivered toxic cargoes and increasing nanoparticle concentrations in avascular peritoneal tumors, little is known about the mechanism of nanoparticle accumulation on tumor tissues and currently, no nanoparticle-based product has been approved for intraperitoneal delivery. Here, we investigated the nanoparticle-specific characteristics that led to increased peritoneal tumor accumulation using MCM-41 type mesoporous silica nanoparticles as our model system. We also investigated the components of the peritoneal tumor stroma that facilitated nanoparticle-tumor interaction. The tumor extracellular matrix is the main factor driving these interactions, specifically the interaction of nanoparticles with collagen. Upon disruption of the collagen matrix, nanoparticle accumulation was reduced by 50%. It is also notable that the incorporation of targeting ligands did not increase overall tumor accumulation in vivo while it significantly increased nanoparticle accumulation in vitro. The use of other particle chemistries did not grossly affect the tumor targetability, but additional concerns arose when those tested particles exhibited significant systemic exposure. Mesoporous silica nanoparticles are advantageous for intraperitoneal administration for the treatment of peritoneal metastasis due to their physical stability, tumor targetability, strong interaction with the collagen matrix, and extended peritoneal residence time. Maximizing nanoparticle interaction with the tumor extracellular matrix is critical for developing strategies to deliver emerging therapeutics for peritoneal cancer treatment using nanocarriers., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Oxytocin (OT) continues to inspire much research due to its diverse physiological effects. While the best-understood actions of OT are uterine contraction and milk ejection, OT is also implicated in maternal and bonding behaviors, and potentially in CNS disorders such as autism, schizophrenia, and pain. The dissection of the mechanism of action of OT is complicated by the fact that this peptide activates not only its cognate receptor but also vasopressin type 1a (V1a) receptors. In this study, we evaluated OT and a selective OT receptor (OTR) agonist, FE 204409, in an automated assay that measures rat locomotor activity. The results showed: 1) Subcutaneous (sc) administration of OT decreased locomotor behavior (distance traveled, stereotypy, and rearing). This effect was reversed by a V1a receptor (V1aR) antagonist ([Pmp1,Tyr(ME)2]AVP, sc), suggesting that OT acts through peripheral V1aR to inhibit locomotor activity. 2) A selective OTR agonist (FE 204409, sc) increased stereotypy. This effect was reversed by an OTR antagonist dosed icv, suggesting a central OTR site of action. Our findings identify distinct behavioral effects for OT and the selective agonist FE 204409, adding to the growing body of evidence that the V1aR mediates many effects attributed to OT and that peptides administered systemically at supra-physiological doses may activate receptors in the brain. Our studies further emphasize the importance of utilizing selective agonists and antagonists to assess therapeutic indications., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objective: To investigate a targeted set of biochemical biomarkers as predictors of clinically relevant osteoarthritis (OA) progression., Methods: Eighteen biomarkers were measured at baseline, 12 months (M) and 24 M in serum (s) and/or urine (u) of cases (n=194) from the OA initiative cohort with knee OA and radiographic and persistent pain worsening from 24 to 48 M and controls (n=406) not meeting both end point criteria. Primary analyses used multivariable regression models to evaluate the association between biomarkers (baseline and time-integrated concentrations (TICs) over 12 and 24 M, transposed to z values) and case status, adjusted for age, sex, body mass index, race, baseline radiographic joint space width, Kellgren-Lawrence grade, pain and pain medication use. For biomarkers with adjusted p<0.1, the c-statistic (area under the curve (AUC)), net reclassification index and the integrated discrimination improvement index were used to further select for hierarchical multivariable discriminative analysis and to determine the most predictive and parsimonious model., Results: The 24 M TIC of eight biomarkers significantly predicted case status (ORs per 1 SD change in biomarker): sCTXI 1.28, sHA 1.22, sNTXI 1.25, uC2C-HUSA 1.27, uCTXII, 1.37, uNTXI 1.29, uCTXIα 1.32, uCTXIβ 1.27. 24 M TIC of uCTXII (1.47-1.72) and uC2C-Human Urine Sandwich Assay (HUSA) (1.36-1.50) both predicted individual group status (pain worsening, joint space loss and their combination). The most predictive and parsimonious combinatorial model for case status consisted of 24 M TIC uCTXII, sHA and sNTXI (AUC 0.667 adjusted). Baseline uCTXII and uCTXIα both significantly predicted case status (OR 1.29 and 1.20, respectively)., Conclusions: Several systemic candidate biomarkers hold promise as predictors of pain and structural worsening of OA., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Intraperitoneal internal radiation therapy is a cancer treatment option that is employed in situations where surgical resection, systemic chemotherapy, and external beam radiotherapy are not amenable for patients. However, exposure of noncancerous tissues to radiation continues to be a hindrance to safe and effective treatment of patients. In addition, reducing prolonged radiation exposure of personnel during preparation of internal radiation therapy agents makes their manufacture complicated and hazardous. Developments in nanotechnology have provided a platform for targeted treatments that combine dual imaging and treatment capabilities all in one package, while also being robust enough to withstand the intense stresses faced during neutron activation. Here, we describe a method for synthesizing neutron activatable mesoporous silica nanoparticles for use in radiotherapy of metastatic peritoneal cancers while limiting personal exposure to radioactive materials, limiting the leakage of radioactive isotopes caused by nanoparticle degradation during neutron activation, and increasing cancer tissue specificity of radiation.

Compton radiography provides a means to measure the integrity, ρR and symmetry of the DT fuel in an inertial confinement fusion implosion near peak compression. Upcoming experiments at the National Ignition Facility will use the ARC (Advanced Radiography Capability) laser to drive backlighter sources for Compton radiography experiments and will use the newly commissioned AXIS (ARC X-ray Imaging System) instrument as the detector. AXIS uses a dual-MCP (micro-channel plate) to provide gating and high DQE at the 40-200 keV x-ray range required for Compton radiography, but introduces many effects that contribute to the spatial resolution. Experiments were performed at energies relevant to Compton radiography to begin characterization of the spatial resolution of the AXIS diagnostic.

Mesoporous silica nanoparticles (MSNs) containing paclitaxel for intraperitoneal (i.p.) delivery were developed to exploit the tumor specific accumulation of these nanocarriers after i.p. injection and the slow release of paclitaxel from the MSNs. A 3.5-fold increase in tumor cellular drug uptake was observed for the paclitaxel-loaded MSNs compared with free paclitaxel. An in vivo study using xenograft mice bearing peritoneal human pancreatic carcinoma MIA PaCa-2 demonstrated that the MSN-paclitaxel formulation, compared to free paclitaxel, exhibited a 3.2-fold increase in peritoneal cavity residence time, slower absorption into the systemic circulation with one third systemic exposure, but a 6.5-fold increase in peritoneal tumor accumulation. Tissue distribution imaging showed significantly greater accumulation of fluorescent MSNs in tumor tissues compared to other peritoneal tissues. In conclusion, intraperitoneal administration of drug-containing MSNs was effective at reducing systemic exposure and increasing the peritoneal tumor accumulation of paclitaxel., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Bovine serum albumin (BSA) microspheres were prepared through a facile and low-cost route including a high-speed dispersion of BSA in cross-linking solution followed by spray drying. Interestingly the as-prepared BSA microspheres possess unique blue-green, green, green-yellow, and red fluorescence when excited by specific wavelengths of laser or LED light. The studies of UV-visible reflectance spectra and fluorescence emission spectra indicated that four classes of fluorescent compounds are presumably formed during the fabrication processes. The formation and the potential contributors for the unique green and red autofluorescence were also discussed and proposed though the exact structures of the fluorophores formed remain elusive due to the complexity of the protein system. The effect of spray-drying conditions on the morphology of spray-dried samples was investigated and optimized. FTIR was further employed to characterize the formation of the functional groups in the as-prepared autofluorescent microspheres. Good in vitro and in vivo biocompatibility was demonstrated by the cytotoxicity test on the A549 cancer cells and tissue histological analysis, respectively. The autofluorescent BSA microspheres themselves were then applied as a novel tracer for convenient tracking/modeling of the biodegradation of autofluorescent BSA microspheres injected into mouse model based on noninvasive, time-dependent fluorescence images of the mice, in which experimental data are in good agreement with the proposed mathematical model. All these studies indicate that the as-developed protein microspheres exhibiting good biocompatibility, biodegradability, and unique autofluorescence, can significantly broaden biomedical applications of fluorescent protein particles.

We previously reported the development of an amphiphilic brush-like block copolymer composed of polynorbornene-cholesterol/polyethylene glycol (P(NBCh9-b-NBPEG)) that self-assembles in aqueous media to form long circulating nanostructures capable of encapsulating doxorubicin (DOX-NPs). Biodistribution studies showed that this formulation preferentially accumulates in tumor tissue with markedly reduced accumulation in the heart and other major organs. The aim of the current study was to evaluate the in vivo efficacy and toxicity of DOX containing self-assembled polymer nanoparticles in a mouse xenograft tumor model and compare its effects with the hydrochloride non-encapsulated form (free DOX). DOX-NPs significantly reduced the growth of tumors without inducing any apparent toxicity. Conversely, mice treated with free DOX exhibited significant weight loss, early toxic cardiomyopathy, acute toxic hepatopathy, reduced hematopoiesis and fatal toxicity. The improved safety profile of the polymeric DOX-NPs can be explained by the low circulating concentration of non-nanoparticle-associated drug as well as the reduced accumulation of DOX in non-target organs. These findings support the use of P(NBCh9-b-NBPEG) nanoparticles as delivery platforms for hydrophobic anticancer drugs intended to reduce the toxicity of conventional treatments., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Because of its good biocompatibility and biodegradability, albumins such as bovine serum albumin (BSA) and human serum albumin (HSA) have found a wide range of biomedical applications. Herein, we report that glutaraldehyde cross-linked BSA (or HSA) forms a novel fluorescent biological hydrogel, exhibiting new green and red autofluorescence in vitro and in vivo without the use of any additional fluorescent labels. UV-vis spectra studies, in conjunction with the fluorescence spectra studies including emission, excitation and synchronous scans, indicated that three classes of fluorescent compounds are presumably formed during the gelation process. SEM, FTIR and mechanical tests were further employed to investigate the morphology, the specific chemical structures and the mechanical strength of the as-prepared autofluorescent hydrogel, respectively. Its biocompatibility and biodegradability were also demonstrated through extensive in vitro and in vivo studies. More interestingly, the strong red autofluorescence of the as-prepared hydrogel allows for conveniently and non-invasively tracking and modeling its in vivo degradation based on the time-dependent fluorescent images of mice. A mathematical model was proposed and was in good agreement with the experimental results. The developed facile strategy to prepare novel biocompatible and biodegradable autofluorescent protein hydrogels could significantly expand the scope of protein hydrogels in biomedical applications.

Amphiphilic brush-like block copolymers composed of polynorbonene-cholesterol/poly(ethylene glycol) (P(NBCh9-b-NBPEG)) self-assembled to form a long circulating nanostructure capable of encapsulating the anticancer drug doxorubicin (DOX) with high drug loading (22.1% w/w). The release of DOX from the DOX-loaded P(NBCh9-b-NBPEG) nanoparticles (DOX-NPs) was steady at less than 2% per day in PBS. DOX-NPs were effectively internalized by human cervical cancer cells (HeLa) and showed dose-dependent cytotoxicity, whereas blank nanoparticles were noncytotoxic. The DOX-NPs demonstrated a superior in vivo circulation time relative to that of free DOX. Tissue distribution and in vivo imaging studies showed that DOX-NPs preferentially accumulated in tumor tissue with markedly reduced accumulation in the heart and other vital organs. The DOX-NPs greatly improved survival and significantly inhibited tumor growth in tumor-bearing SCID mice compared to that for the untreated and free DOX-treated groups. The results indicated that self-assembled P(NBCh9-b-NBPEG) may be a useful carrier for improving tumor delivery of hydrophobic anticancer drugs.

Recently developed diagnostic techniques at LLNL require recording backlit images of extremely dense imploded plasmas using hard x-rays, and demand the detector to be sensitive to photons with energies higher than 50 keV [R. Tommasini et al., Phys. Phys. Plasmas 18, 056309 (2011); G. N. Hall et al., "AXIS: An instrument for imaging Compton radiographs using ARC on the NIF," Rev. Sci. Instrum. (these proceedings)]. To increase the sensitivity in the high energy region, we propose to use a combination of two MCPs. The first MCP is operated in a low gain regime and works as a thick photocathode, and the second MCP works as a high gain electron multiplier. We tested the concept of this dual MCP configuration and succeeded in obtaining a detective quantum efficiency of 4.5% for 59 keV x-rays, 3 times larger than with a single plate of the thickness typically used in NIF framing cameras.

An immune response to recombinant human protein therapeutics, including type I interferons (IFNs), has the potential to have a serious negative impact on safety and efficacy. Monitoring of patients for neutralizing antibodies (NAbs) often is advisable. In the case of IFN-beta therapy for multiple sclerosis (MS), we obtained reproducible quantitative titers of NAbs using an improved and well-characterized assay based on a 10-fold reduction of a challenge dose of IFN-beta. However, the observed titer was significantly affected by the preparation of IFN-beta used as the assay challenge. NAb titers obtained using IFN-beta1b averaged 3-5-fold lower than titers of the same sample assayed using either IFN-beta1a or human fibroblast-derived IFN-beta. This was the case whether neutralizing serum was obtained from patients on therapy with IFN-beta1a or IFN-beta1b. The reason for this apparent titer difference is not fully understood but appears to be related to protein folding or other structural properties that differentiate the IFN-beta1b both from commercial IFN-beta1a preparations and from human fibroblast-derived IFN-beta.

The Louisiana Office of Public Health Tobacco Control and Prevention Program received funding from the Louisiana State Legislature to expand smoking cessation activities in the state. The Tobacco Control Program conducted a review of other states' current smoking cessation programs, cessation programs in Louisiana, and epidemiological evidence in planning the expansion of the Louisiana tobacco smoking cessation program. As a result, a smoking cessation helpline has been developed. Medical clinicians in Louisiana have a powerful impact on their patients' smoking cessation success. Simple discussion by physicians with their patients about how to quit smoking has improved successful quitting rates by 40%. Approximately 70% of smokers visit a physician each year and 60% visit a dentist, so there is clearly an opportunity to reach many persons at risk. The telephone smoking cessation helpline at 1-800-LUNG-USA is a tool for clinicians to use when advising their patients on ways to improve their health and prevent disease.

Type 2 diabetes mellitus (T2DM) is strongly inherited, but the major genes for this disease have been elusive. In contrast, early-onset, autosomal-dominant diabetes results from at least 5 loci, of which hepatocyte nuclear factor 1a (HNF1alpha or TCF1) is the most common cause. Mutations in HNF1alpha also cause later-onset diabetes in some Caucasian populations, but the role of these mutations has not been tested in African American populations. We used a variety of screening methods, including both single-strand conformation polymorphism (SSCP) analysis and dideoxy fingerprint analysis, to search for mutations in 51 African American subjects with onset of diabetes before age 50 years. Potential mutations were confirmed by direct sequencing. We identified 21 different variants, of which 11 were unique to African Americans. Four mutations either altered the amino acid sequence (Gly52Ala and Gly574Ser) or were close to a splice site (intron 1 and intron 10). A 5-nucleotide insertion in intron 1 was present in both diabetic members of a small family, but Gly52Ala, Gly574Ser, and the intron 10 mutation did not segregate with diabetes. Gly574Ser was present in 2 large families and 5% of controls, all of which appeared to share the same common HNF1alpha haplotype. Surprisingly, radioactive SSCP analysis under 2 room-temperature conditions performed as well as methods using fluorescent labeling that were expected to be more sensitive. We conclude that in African American individuals under age 50, variation in the HNF1a gene is common but unlikely to be a significant cause of T2DM.

We used focus groups to learn the range of issues threatening food security of low income residents in our community. Five major themes emerged from the discussions: literacy, money, time, mental health and self-esteem, suggesting several approaches that could help ensure food security: 1) education, 2) sharing of resources, 3) coalition building, and 4) advocacy. Education programs have to be practical, allowing for demonstrations and hands-on learning while emphasizing skill building and problem solving. Incorporating a social aspect into learning may compensate for the social isolation and would capitalize on the impressive mutual support we witnessed. Strategies based on self-help and peer assistance may counteract low self-esteem and overcome suspicion of health professionals. A community-wide effort is needed to address the factors contributing to food insecurity. We envision the formation of a coalition of professionals, agencies, and low income people to develop a comprehensive strategy for achieving food security.

Circulating human immunodeficiency virus (HIV) p24 antigen levels were measured by a highly sensitive HIV p24 antigen-capture enzyme-linked immunosorbent assay (ELISA) in patients with acquired immunodeficiency syndrome (AIDS) and AIDS-related complex (ARC) otherwise negative for HIV p24 antigen measured by a commercial antigen-capture ELISA. The assays were performed at baseline and at several intervals during treatment with either zidovudine (ZDV) or dideoxyinosine (ddl). To further enhance the rate of antigen detection, serum was pretreated with hydrochloric acid to denature antibody in immune complexes. Utilizing this assay system, we monitored these patients for drug efficacy. HIV p24 antigen levels obtained by using this sensitive assay decreased in 3 of 8 patients receiving ZDV during 8 weeks of ZDV treatment. Similarly, ddl administration was associated with a decrease of HIV p24 antigen levels in 3 of 5 patients. Thus, the use of the highly sensitive HIV p24 antigen assay permitted the monitoring of surrogate HIV p24 antigen as a measure of efficacy of anti-retroviral therapy in all of these patients who were otherwise HIV p24 antigen-negative at the onset of anti-retroviral therapy.

The essentiality of dietary arginine was examined in adult humans with three biochemical indices: plasma levels of ammonium and amino acids and urinary orotic acid excretion. Three male and two female subjects participated in the 10-d study. Subjects consumed an L-amino acid diet containing 0.74 g protein equivalent/kg body weight on d 1-5; these amino acid concentrations were doubled on d 6-10. The diet was devoid of arginine on d 3-8. Daily urine was collected and blood samples were drawn on 6 of the 10 d at 0, 0.5, 1, 2, 3 and 4 h after the breakfast meal. When arginine was removed from the diet, urinary orotic acid did not increase, in contrast to what has been reported in most other animal species tested. Plasma ammonium concentrations remained within normal limits throughout the study. A small postprandial decrease in plasma arginine concentration was observed when the arginine-deficient diet was consumed; this decline disappeared when the diet was resupplied with arginine. The results of this study suggest that over the short term the adult human's capacity for de novo arginine synthesis when fed a dietary deficiency of arginine is sufficient for the maintenance of normal cellular metabolism.