Mesenchymal Stromal Cells: a Possible Reservoir for HIV-1?

The introduction of antiretroviral therapy (ART) and highly active antiretroviral therapy (HAART) has transformed human immunodeficiency virus (HIV)-1 into a chronic, well-managed disease. However, these therapies do not eliminate all infected cells from the body despite suppressing viral load. Viral rebound is largely due to the presence of cellular reservoirs which support long-term persistence of HIV-1. A thorough understanding of the HIV-1 reservoir will facilitate the development of new strategies leading to its detection, reduction, and elimination, ultimately leading to curative therapies for HIV-1. Although immune cells derived from lymphoid and myeloid progenitors have been thoroughly studied as HIV-1 reservoirs, few studies have examined whether mesenchymal stromal/stem cells (MSCs) can assume this function. In this review, we evaluate published studies which have assessed whether MSCs contribute to the HIV-1 reservoir. MSCs have been found to express the receptors and co-receptors required for HIV-1 entry, albeit at levels of expression and receptor localisation that vary considerably between studies. Exposure to HIV-1 and HIV-1 proteins alters MSC properties in vitro, including their proliferation capacity and differentiation potential. However, in vitro and in vivo experiments investigating whether MSCs can become infected with and harbour latent integrated proviral DNA are lacking. In conclusion, MSCs appear to have the potential to contribute to the HIV-1 reservoir. However, further studies are needed using techniques such as those used to prove that cluster of differentiation (CD)4+ T cells constitute an HIV-1 reservoir before a reservoir function can definitively be ascribed to MSCs. MSCs may contribute to HIV-1 persistence in vivo in the vasculature, adipose tissue, and bone marrow by being a reservoir for latent HIV-1. To harbour latent HIV-1, MSCs must express HIV-1 entry markers, and show evidence of productive or latent HIV-1 infection. The effect of HIV-1 or HIV-1 proteins on MSC properties may also be indicative of HIV-1 infection.

Peripheral access options.

With the dramatic downsizing of acute care facilities and shifting to alternate care settings, infusion therapy is a major aspect of outpatient and home health services. Health care reform has forced health care practitioners to make cost-driven clinical decisions, while at the same time demanding quality outcomes. Technology has advanced our capabilities to provide infusion therapies in all settings. Controversial questions are asked regarding the selection of the appropriate device, catheter tip position, tip position verification, and care and management techniques, which only well-designed research protocols can answer. In the meantime, clinical decisions must be based on current science and physiologic principles, rather than tradition, anecdotal observation, or competitive financial agendas. Peripheral access catheters, if widely used, afford a tremendous opportunity for positive outcomes and cost savings.

Venous access device utilization in home care settings.

Home infusion therapy is the fastest growing segment of home care, yet little is known about the utilization of various venous access devices in the home. This study reports pioneering data from thirty seven hospital-based, community-based and home infusion pharmacy agencies across the country which provide home infusion therapy services. Venous access device utilization data for adults and children are compared and differences among agency types of home care providers are analyzed. Significant patient device utilization differences among different provider types and age groups are discussed in terms of their implications for clinicians, educators, policy makers and researchers.

Peripherally inserted central venous catheters.

It has been estimated that 5 million central venous catheters are used in the United States each year. The medical market has been inundated with vascular access devices representing phenomenal advancement in catheter technology. These devices are not without serious risk, however, and they require constant vigilance and scrupulous care to prevent life-threatening complications. Nursing care and management of these devices are complex, and many controversial practice issues challenge nursing practitioners. The insertion of central venous catheters by registered nurses is a relatively new adventure in nursing practice, increasing our professional responsibility, accountability, and liability. Scientific principles and research must direct our practice and our decisions. The challenge is to seize this opportunity to develop a new concept in IV therapy based on nursing research.

Vascular access devices: perspectives on designs, complications, and management.

The use of vascular access devices in hospitalized and home care patients has expanded rapidly in the past decade. New designs, materials, insertion techniques, and protocols for care related to vascular access devices have emerged. Complications associated with them, however, have remained a persistent problem. Septicemia, thrombosis, and occlusion are three of the more serious complications that can lead to the need for removal of the device. These complications are reviewed and areas for future research are identified.

Multilumen catheter sepsis and an educational program to combat it.

Catheter-related sepsis is a problem with many variables. A process of elimination may eventually identify the actual cause(s) of this phenomenon. We began our problem-solving approach by observing personnel inserting and caring for central lines, which showed a lack of compliance with existing protocols. A program was designed to provide the correct procedural activities. This study plans to test whether ongoing educational programs and an infection control department that maintains a high degree of visibility are effective in reducing nosocomial line-related infections.

Complications of parenteral nutrition.

All hospitalized patients except infants (a total of 1,647 patients) who received central venous TPN solutions at UCDMC from 1981 through 1985 were studied to determine the incidence of complications from the use of TPN. A complication was considered to have occurred if the patient experienced obvious morbidity, mortality, or both; an event known to be deleterious, despite a lack of demonstrable morbidity; or premature loss of the central venous catheter. Complications related to catheter placement occurred in 5.7 percent of patients, sepsis in 6.5 percent, mechanical complications in 9 percent, and metabolic complications in 7.7 percent. The incidence of induction of sepsis increased during 1984 to 1985 due to the introduction of multilumen central venous catheters. The most frequent catheter placement complications were hemorrhage and pneumothorax. Major venous thrombosis and nursing mishaps were the most common mechanical complications. Metabolic complications were infrequent and were generally not severe after adjustment of the protocol in late 1981. Four patients (0.2 percent) died from TPN-associated complications: a child on home TPN who underwent a catheter change and in whom hyperosmolar hyperglycemic coma developed, a patient with end-stage chronic obstructive pulmonary disease in whom tension pneumothorax occurred, a patient who died from complications of subclavian artery laceration, and a patient who died from Candida septicemia. Complications of TPN are frequent and may be severe. Quality assurance mechanisms for identification of these complications are necessary and should form the basis for the establishment of appropriate protocols.

Synthesis of the antileukemic compound N,N(11)-[5-[bis(2-chloroethyl)amino]-1, 3-phenylene]bisurea.

Conversion of 5-nitro-1, 3-benzenedicarboxylic acid (1) to the diamide 2 followed by hypochlorite rearrangement to the idamine 3 and subsequent reaction with acetic anhydride gave the bisacetamide 4. Reduction to the amine 5 followed by treatment with ethylene oxide formed the diol 6. The latter was converted to the bistosylate 7, which undrewent facile displacement with lithium chloride in acetone to give the mustard 8. Removal of the acetyl groups with hydrochloric acid gave 9, which reacted with potassium cyanate to provide the bisurea 10. In an alternative, but less satisfactory synthesis of 10, the compound (5-nitro-1, 3-phenylene) biscarbamic acid diphenyl ester (11), or the corresponding diethyl ester 12, was converted by ammonolysis to 13. The nitrodiurea 13 was next reduced to the amine 14, the hydrochloride of which reacted with ethylene oxide to give the diol 15. Treatment of the latter in dimethylformamide with N-chlorosuccinimide in the presence of triphenylphosphine gave 10 in low yield. The nitrogen mustards 8, 9 and 10 showed significant antitumor activities against P388 lymphocytic leukemia in mice.