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1

Therapeutic immunization for HIV.  

PubMed

Vaccines have entered into human clinical trials against infectious diseases and as therapies against cancer. The HIV virus establishes a latent infection at a very early stage and the T cell memory of the infected patient is rapidly destroyed. However, results of immunotherapy after DNA and protein immunization show that vaccine-induced immune responses might be present for a long period of time. Patients subjected to therapeutic immunization appear to do well, and to have a small immunological advantage, which, however, will have to be improved. The vaccine therapy should start early, while adequate reservoirs of appropriate T helper cells are available and still inducible. The DNA vaccines induce a relatively long-lived immunological memory, and gene-based immunization is effective in inducing cytotoxic CD8(+) T cells and CD4+ helper cells. Protein vaccines, on the other hand, primarily give T cell help. It thus appears that DNA and protein approaches to HIV immunization complement each other. A surprisingly broad reactivity to peptides from different subtypes of HIV was identified in individuals infected with several subtypes of HIV. PMID:17031650

Gudmundsdotter, Lindvi; Sjödin, Anna; Boström, Ann-Charlotte; Hejdeman, Bo; Theve-Palm, Rebecca; Alaeus, Annette; Lidman, Knut; Wahren, Britta

2006-11-01

2

Therapeutic HIV Vaccines What is a vaccine?  

E-print Network

Therapeutic HIV Vaccines What is a vaccine? A vaccine is a medical product designed to stimulate there are currently no vaccines to prevent or treat HIV, researchers are developing and testing potential HIV vaccines. HIV vaccines designed to prevent HIV infection in HIV negative people are called preventive vaccines

Levin, Judith G.

3

Conotoxins that Confer Therapeutic Possibilities  

PubMed Central

Cone snails produce a distinctive repertoire of venom peptides that are used both as a defense mechanism and also to facilitate the immobilization and digestion of prey. These peptides target a wide variety of voltage- and ligand-gated ion channels, which make them an invaluable resource for studying the properties of these ion channels in normal and diseased states, as well as being a collection of compounds of potential pharmacological use in their own right. Examples include the United States Food and Drug Administration (FDA) approved pharmaceutical drug, Ziconotide (Prialt®; Elan Pharmaceuticals, Inc.) that is the synthetic equivalent of the naturally occurring ?-conotoxin MVIIA, whilst several other conotoxins are currently being used as standard research tools and screened as potential therapeutic drugs in pre-clinical or clinical trials. These developments highlight the importance of driving conotoxin-related research. A PubMed query from 1 January 2007 to 31 August 2011 combined with hand-curation of the retrieved articles allowed for the collation of 98 recently identified conotoxins with therapeutic potential which are selectively discussed in this review. Protein sequence similarity analysis tentatively assigned uncharacterized conotoxins to predicted functional classes. Furthermore, conotoxin therapeutic potential for neurodegenerative disorders (NDD) was also inferred. PMID:22822370

Essack, Magbubah; Bajic, Vladimir B.; Archer, John A. C.

2012-01-01

4

[Therapeutic possibilities after traumatic experiences].  

PubMed

Acute stress disorder (ASD) and posttraumatic stress disorder (PTSD) are frequent, but not obligatory psychological sequelae following trauma. A major subgroup of patients face a chronic course of illness associated with an increased psychiatric comorbidity and significant impairments in psychosocial adaptation. The typical psychopathological symptoms of ASD and PTSD are best described within a multifactorial model integrating both neurobiological and psychosocial influences. The complex etiopathogenesis of acute and posttraumatic stress disorder favours multimodal approaches in the treatment. Differential psychotherapeutic and pharmacological strategies are available. In a critical survey on empirical studies, psychological debriefing cannot be considered as a positive approach to be recommended as general preventive measure during the immediate posttraumatic phase. Positive effects of cognitive-behavioral interventions can be established for ASD. Psychodynamic psychotherapy, cognitive-behavioral therapy and EMDR show promising results in the treatment of PTSD. Major clinical restrictions of patient sampling within special research facilities, however, do not allow an unconditional generalization of these data to psychiatric routine care. In an empirical analysis the SSRIs are the most and best studied medications for ASD and PTSD. In comparison to tricyclic antidepressants SSRIs demonstrate a broader spectrum of therapeutic effects and are better tolerated. The substance classes of SSNRI, DAS, SARI and NaSSA are to be considered as drugs of second choice. They promise a therapeutic efficacy equivalent to the SSRIs, being investigated so far only in open studies. MAO-inhibitors may dispose of a positive therapeutic potential, their profile of side effects must be respected, however. Mood stabilizers and atypical neuroleptics may be used first and foremost in add-on strategies. Benzodiazepines should be used only with increased caution for a short time in states of acute crisis. In early interventions, substances blocking the norepinephric hyperactivity seem to be promising alternatives. Stress doses of hydrocortisone may be considered as an experimental pharmacological strategy so far. PMID:19011595

Kapfhammer, Hans-Peter

2008-12-01

5

Putting an 'End' to HIV mRNAs: capping and polyadenylation as potential therapeutic targets.  

PubMed

Like most cellular mRNAs, the 5' end of HIV mRNAs is capped and the 3' end matured by the process of polyadenylation. There are, however, several rather unique and interesting aspects of these post-transcriptional processes on HIV transcripts. Capping of the highly structured 5' end of HIV mRNAs is influenced by the viral TAT protein and a population of HIV mRNAs contains a trimethyl-G cap reminiscent of U snRNAs involved in splicing. HIV polyadenylation involves active repression of a promoter-proximal polyadenylation signal, auxiliary upstream regulatory elements and moonlighting polyadenylation factors that have additional impacts on HIV biology outside of the constraints of classical mRNA 3' end formation. This review describes these post-transcriptional novelties of HIV gene expression as well as their implications in viral biology and as possible targets for therapeutic intervention. PMID:24330569

Wilusz, Jeffrey

2013-01-01

6

Therapeutic dendritic-cell vaccine for chronic HIV1 infection  

Microsoft Academic Search

We present the results of a preliminary investigation of the efficacy of a therapeutic dendritic cell (DC)-based vaccine for HIV-1. We immunized 18 chronically HIV-1-infected and currently untreated individuals showing stable viral loads for at least 6 months with autologous monocyte-derived DCs loaded with autologous aldrithiol-2-inactivated HIV-1. Plasma viral load levels were decreased by 80% (median) over the first 112

Luiz Claudio Arraes; Wylla Tatiana Ferreira; Wei Lu; Jean-Marie Andrieu

2004-01-01

7

Fighting HIV/AIDS: is success possible?  

PubMed Central

The fight against HIV/AIDS poses enormous challenges worldwide, generating fears that success may be too difficult or even impossible to attain. Uganda has demonstrated that an early, consistent and multisectoral control strategy can reduce both the prevalence and the incidence of HIV infection. From only two AIDS cases in 1982, the epidemic in Uganda grew to a cumulative 2 million HIV infections by the end of 2000. The AIDS Control Programme established in 1987 in the Ministry of Health mounted a national response that expanded over time to reach other relevant sectors under the coordinating role of the Uganda AIDS Commission. The national response was to bring in new policies, expanded partnerships, increased institutional capacity for care and research, public health education for behaviour change, strengthened sexually transmitted disease (STD) management, improved blood transfusion services, care and support services for persons with HIV/AIDS, and a surveillance system to monitor the epidemic. After a decade of fighting on these fronts, Uganda became, in October 1996, the first African nation to report declining trends in HIV infection. Further decline in prevalence has since been noted. The Medical Research Council (UK) and the Uganda Virus Research Institute have demonstrated declining HIV incidence rates in the general population in the Kyamulibwa in Masaka Districts. Repeat knowledge, attitudes, behaviour and practice studies have shown positive changes in the priority prevention indicators. The data suggest that a comprehensive national response supported by strong political commitment may be responsible for the observed decline. Other countries in sub-Saharan Africa can achieve similar results by these means. Since success is possible, anything less is unacceptable. PMID:11799443

Okware, S.; Opio, A.; Musinguzi, J.; Waibale, P.

2001-01-01

8

A proposal to use iterative, small clinical trials to optimize therapeutic HIV vaccine immunogens to launch therapeutic HIV vaccine development.  

PubMed

The HIV cure agenda has rekindled interest in the development of a therapeutic HIV vaccine. An iterative clinical trial strategy that proved successful for the development of effective cancer chemotherapies in the 1960s may be applicable to the development of a CD8 T lymphocyte-based therapeutic HIV vaccine. However, while cancer chemotherapy development could begin with iterative clinical trials to improve the use of active drugs, the first step in therapeutic HIV vaccine design should be discovery of immunogen constructs with potential for activity and their optimization to meet the challenges of HIV-1 sequence diversity and human polymorphism in T cell antigen presentation. A strategy for doing this is discussed in this article. The proposed strategy relies on a major commitment by funding organizations to fund organized and coordinated manufacture and clinical testing of a series of first- and second-generation constructs to test basic concepts in product design. This is presented as an alternative to funding a more traditional competition among private manufacturers and product champions of individual, already designed products. PMID:25286142

Shapiro, Stuart Z

2015-01-01

9

The structural biology of HIV-1: mechanistic and therapeutic insights  

PubMed Central

Three-dimensional molecular structures can provide detailed information on biological mechanisms and, in cases where molecular function impacts on human health, significantly aid in the development of therapeutic interventions. Over the past 23 years, key components of the lentivirus HIV-1, including its envelope glycoproteins and capsid, and the replication enzymes reverse transcriptase, integrase and protease, have accordingly been scrutinized to near atomic scale resolution. Structural analyses of the interactions between viral and host cell components have moreover yielded key insights into the mechanisms of virus entry, chromosomal integration, transcription and egress from cells. Here, we review recent advances in HIV-1 structural biology, focusing on the impact these results have had on our understanding of virus replication and the development of new therapeutics. PMID:22421880

Engelman, Alan; Cherepanov, Peter

2013-01-01

10

HIV Preclinical-Clinical Therapeutics Research: central nervous system approaches.  

PubMed

The prevalence of HIV-associated brain disorders is reportedly increasing due, in part, to the prolonged life span of individuals who are surviving well on highly active antiretroviral treatments (HAART). While clinicians report CNS-related deficits that are more subtle in presentation than the frank dementia evident in the pre-HAART era, the milder presentation continues to substantively reduce an individual's quality of life. The development of novel drugs or therapeutic strategies for treating HIV-related CNS disease is important as most investigators agree that the brain is a sanctuary for latent virus, local viral recrudescence, and associated brain inflammatory responses. The prolonged chronic and cumulative effects on the brain of living with HIV-related inflammatory processes, antiretroviral treatments, and their long-term side effects, toxicities, and brain-related aging processes collectively indicate that the burden of CNS and PNS complications will increase profoundly during the upcoming years. Considering the high expense for new drugs entering CNS-related clinical trials and their ultimately low success rate, the NIMH convened a meeting entitled, HIV Preclinical-Clinical Therapeutics Research Meeting, to discuss the current and proposed novel approaches for neuroAIDS drug development and clinical practices. The purposes of the meeting were twofold: to identify the most promising approaches for future neuroAIDS therapeutics development research and to discuss optimal structures and partnerships with industry that may facilitate the successful movement of compounds from the bench to the bedside. Several themes can be derived from the sessions and are highlighted below for preclinical, translational and clinical neuroAIDS therapeutics research. PMID:18040818

Kopnisky, Kathy L; Bao, Jing

2007-03-01

11

Parasitic infections in HIV infected individuals: Diagnostic & therapeutic challenges  

PubMed Central

After 30 years of the human immunodeficiency virus (HIV) epidemic, parasites have been one of the most common opportunistic infections (OIs) and one of the most frequent causes of morbidity and mortality associated with HIV-infected patients. Due to severe immunosuppression, enteric parasitic pathogens in general are emerging and are OIs capable of causing diarrhoeal disease associated with HIV. Of these, Cryptosporidium parvum and Isospora belli are the two most common intestinal protozoan parasites and pose a public health problem in acquired immunodeficiency syndrome (AIDS) patients. These are the only two enteric protozoan parasites that remain in the case definition of AIDS till today. Leismaniasis, strongyloidiasis and toxoplasmosis are the three main opportunistic causes of systemic involvements reported in HIV-infected patients. Of these, toxoplasmosis is the most important parasitic infection associated with the central nervous system. Due to its complexity in nature, toxoplasmosis is the only parasitic disease capable of not only causing focal but also disseminated forms and it has been included in AIDS-defining illnesses (ADI) ever since. With the introduction of highly active anti-retroviral therapy (HAART), cryptosporidiosis, leishmaniasis, schistosomiasis, strongyloidiasis, and toxoplasmosis are among parasitic diseases reported in association with immune reconstitution inflammatory syndrome (IRIS). This review addresses various aspects of parasitic infections in term of clinical, diagnostic and therapeutic challenges associated with HIV-infection. PMID:22310820

Nissapatorn, Veeranoot; Sawangjaroen, Nongyao

2011-01-01

12

Novel anti-HIV therapeutics targeting chemokine receptors and actin regulatory pathways  

PubMed Central

Summary The human immunodeficiency virus-1 (HIV-1) infects helper CD4+ T cells, and causes CD4+ T-cell depletion and immunodeficiency. In the past 30 years, significant progress has been made in antiretroviral therapy, and the disease has become manageable. Nevertheless, an effective vaccine is still nowhere in sight, and a cure or a functional cure awaits discovery. Among possible curative therapies, traditional antiretroviral therapy, mostly targeting viral proteins, has been proven ineffective. It is possible that targeting HIV-dependent host cofactors may offer alternatives, both for preventing HIV transmission and for forestalling disease progression. Recently, the actin cytoskeleton and its regulators in blood CD4+ T cells have emerged as major host cofactors that could be targeted. The novel concept that the cortical actin is a barrier to viral entry and early post-entry migration has led to the nascent model of virus-host interaction at the cortical actin layer. Deciphering the cellular regulatory pathways has manifested exciting prospects for future therapeutics. In this review, we describe the study of HIV interactions with actin cytoskeleton. We also examine potential pharmacological targets that emerge from this interaction. In addition, we briefly discuss several actin pathway-based anti-HIV drugs that are currently in development or testing. PMID:24117829

Spear, Mark; Guo, Jia; Wu, Yuntao

2013-01-01

13

An HIV-1 transmission case possibly associated with manicure care.  

PubMed

A recently diagnosed 22-year-old female with no history of transmission risk factors prompted a thorough investigation of possible alternative risk factors. As the patient had evidence of advanced disease and laboratory data compatible with long-standing infection, past events were reviewed. About 10 years ago the patient shared manicure utensils with an older cousin, later known to be HIV infected; this prompted the phylogenetic analysis of the HIV sequences of both patients. Phylogenetic analyses of partial HIV-1 polymerase and envelope sequences from both patients revealed highly related sequences, with an estimated common ancestor date (about 11 years ago) that coincided with the putative sharing of manicure instruments, during a time in which the cousin was not virally suppressed. Taken together, the information about the infection of this patient suggests the use of shared manicure instruments as an alternative route of fomite HIV-1 transmission. PMID:25354026

Matsuda, Elaine Monteiro; Coelho, Luana Portes Ozório; Pimentel, Victor Figueiredo; Onias, Humberto Barjud; Brigido, Luís Fernando de Macedo

2014-11-01

14

HIV-1 protease molecular dynamics of a wild-type and of the V82F/I84V mutant: Possible contributions to drug  

E-print Network

HIV-1 protease molecular dynamics of a wild-type and of the V82F/I84V mutant: Possible immunodeficiency virus (HIV-1) is a critical drug target against which many therapeutically useful inhibitors have water) of both a wild-type and the drug-resistant V82F/I84V mutant of HIV-1 protease. The V82F/I84V

Batzoglou, Serafim

15

Therapeutic immunization with an inactivated HIV-1 Immunogen plus antiretrovirals versus antiretroviral therapy alone in asymptomatic HIV-infected subjects.  

PubMed

To determine whether the addition of an inactivated-gp120-depleted HIV-1 Immunogen to antiretrovirals (ARTs) conferred a beneficial effect on delaying time to virologic failure relative to that obtained by ARTs alone, a phase II clinical trial was performed in 243 asymptomatic, ART naďve, HIV-1 seropositive adults. The Cox model showed that HIV-1 Immunogen treatment was associated with a 34% decrease in the risk of virologic failure (P = 0.056). When the analysis incorporated baseline HIV-RNA stratification the risk of virologic failure in the HIV-1 Immunogen Arm was significantly reduced a 37% compared to the IFA placebo Arm (P = 0.034). The data suggest that therapeutic immunization plus ARTs could influence virologic control. PMID:15297045

Fernandez-Cruz, E; Moreno, S; Navarro, J; Clotet, B; Bouza, E; Carbone, J; Peńa, J M; Pérez Molina, J; Podzamczer, D; Rubio, R; Ocańa, I; Pulido, F; Viciana, P; Maradona, J A; Blazquez, R; Barros, C; Quereda, C; Rodriguez-Sainz, C; Gil, J; Abad, M L; Díaz, L; Cantó, C; Muńoz, M A; Ferrer, E; Jou, A; Sirera, G; Díaz, M; Lopez, F; Gatell, J M; Gonzalez-Lahoz, J

2004-08-13

16

Engineering Cellular Resistance to HIV-1 Infection In Vivo Using a Dual Therapeutic Lentiviral Vector.  

PubMed

We described earlier a dual-combination anti-HIV type 1 (HIV-1) lentiviral vector (LVsh5/C46) that downregulates CCR5 expression of transduced cells via RNAi and inhibits HIV-1 fusion via cell surface expression of cell membrane-anchored C46 antiviral peptide. This combinatorial approach has two points of inhibition for R5-tropic HIV-1 and is also active against X4-tropic HIV-1. Here, we utilize the humanized bone marrow, liver, thymus (BLT) mouse model to characterize the in vivo efficacy of LVsh5/C46 (Cal-1) vector to engineer cellular resistance to HIV-1 pathogenesis. Human CD34+ hematopoietic stem/progenitor cells (HSPC) either nonmodified or transduced with LVsh5/C46 vector were transplanted to generate control and treatment groups, respectively. Control and experimental groups displayed similar engraftment and multilineage hematopoietic differentiation that included robust CD4+ T-cell development. Splenocytes isolated from the treatment group were resistant to both R5- and X4-tropic HIV-1 during ex vivo challenge experiments. Treatment group animals challenged with R5-tropic HIV-1 displayed significant protection of CD4+ T-cells and reduced viral load within peripheral blood and lymphoid tissues up to 14 weeks postinfection. Gene-marking and transgene expression were confirmed stable at 26 weeks post-transplantation. These data strongly support the use of LVsh5/C46 lentiviral vector in gene and cell therapeutic applications for inhibition of HIV-1 infection. PMID:25872029

Burke, Bryan P; Levin, Bernard R; Zhang, Jane; Sahakyan, Anna; Boyer, Joshua; Carroll, Maria V; Colón, Joanna Camba; Keech, Naomi; Rezek, Valerie; Bristol, Gregory; Eggers, Erica; Cortado, Ruth; Boyd, Maureen P; Impey, Helen; Shimizu, Saki; Lowe, Emily L; Ringpis, Gene-Errol E; Kim, Sohn G; Vatakis, Dimitrios N; Breton, Louis R; Bartlett, Jeffrey S; Chen, Irvin S Y; Kitchen, Scott G; An, Dong Sung; Symonds, Geoff P

2015-01-01

17

HIV-1 impairs human retinal pigment epithelial barrier function: possible association with the pathogenesis of HIV-associated retinopathy.  

PubMed

The breakdown of human retinal pigment epithelial (HRPE) barrier is considered as the etiology of retinopathy, which affects the quality of life of HIV/AIDS patients. Here we demonstrate that HIV-1 could directly impair HRPE barrier function, which leads to the translocation of HIV-1 and bacteria. HRPE cells (D407) were grown to form polarized, confluent monolayers and treated with different HIV-1 infectious clones. A significant increase of monolayer permeability, as measured by trans-epithelial electrical resistance (TEER) and apical-basolateral movements of sodium fluorescein, was observed. Disrupted tightness of HRPE barrier was associated with the downregulation of several tight junction proteins in D407 cells, including ZO-1, Occludin, Claudin-1, Claudin-2, Claudin-3, Claudin-4, and Claudin-5, after exposure to HIV-1, without affecting the viability of cells. HIV-1 gp120 was shown to participate in the alteration of barrier properties, as evidenced by decreased TEER and weakened expression of tight junction proteins in D407 monolayers after exposure to pseudotyped HIV-1, UV-inactivated HIV-1, and free gp120, but not to an envelope (Env)-defective mutant of HIV. Furthermore, exposure to HIV-1 particles could induce the release of pro-inflammatory cytokines in D407, including IL-6 and MCP-1, both of which downregulated the expression of ZO-1 in the HRPE barrier. Disrupted HRPE monolayer allowed translocation of HIV-1 and bacteria across the epithelium. Overall, these findings suggest that HIV-1 may exploit its Env glycoprotein to induce an inflammatory state in HRPE cells, which could result in impairment of HRPE monolayer integrity, allowing virus and bacteria existing in ocular fluids to cross the epithelium and penetrate the HRPE barrier. Our study highlights the role of HIV-1 in the pathogenesis of HIV/AIDS-related retinopathy and suggests potential therapeutic targets for this ocular complication. PMID:24840331

Tan, Suiyi; Duan, Heng; Xun, Tianrong; Ci, Wei; Qiu, Jiayin; Yu, Fei; Zhao, Xuyan; Wu, Linxuan; Li, Lin; Lu, Lu; Jiang, Shibo; Liu, Shuwen

2014-07-01

18

CCR6 as a possible therapeutic target in psoriasis  

PubMed Central

Importance of the field Psoriasis is a common, chronic autoimmune disease of the skin. Despite a number of effective treatments, new therapies are needed with enhanced efficacy, safety, and convenience. Chemokine receptors are G protein-coupled receptors that control leukocyte trafficking, and like other G protein-coupled receptors, are good potential drug targets. The chemokine receptor CCR6 is expressed on the Th17 subset of CD4+ T cells, which produces IL-17A/F, IL-22, TNF-? and other cytokines, and which has been implicated in the pathogenesis of psoriasis. CCR6 and its ligand, CCL20/MIP-3?, are highly expressed in psoriatic skin and CCR6 is necessary for the pathology induced in a mouse model of psoriasis-like inflammation. Areas covered in this review This review will summarize the evidence for the importance of the IL-23/Th17 axis, and in particular CCR6 and CCL20 in psoriasis, dating from 2000 to the present, and discuss the possibility of inhibiting CCR6 as treatment for the disease. What the reader will gain The review will inform the reader of the current thinking on the mechanisms of inflammation in psoriasis and the possible roles for CCR6 (and CCL20) in disease pathogenesis. Take home message We conclude that CCR6 should be investigated as a potential therapeutic target in psoriasis. PMID:20629596

Hedrick, Michael N.; Lonsdorf, Anke S.; Hwang, Sam T.; Farber, Joshua M.

2010-01-01

19

HIV Preclinical–Clinical Therapeutics Research: Central Nervous System Approaches  

Microsoft Academic Search

The prevalence of HIV-associated brain disorders is reportedly increasing due, in part, to the prolonged life span of individuals\\u000a who are surviving well on highly active antiretroviral treatments (HAART). While clinicians report CNS-related deficits that\\u000a are more subtle in presentation than the frank dementia evident in the pre-HAART era, the milder presentation continues to\\u000a substantively reduce an individual’s quality of

Kathy L. Kopnisky; Jing Bao

2007-01-01

20

HBV and HIV co-infection: Impact on liver pathobiology and therapeutic approaches.  

PubMed

The consequences of hepatitis B virus (HBV) and human immunodeficiency virus (HIV) co-infection on progression of severe liver diseases is a serious public health issue, worldwide. In the co-infection cases, about 90% of HIV-infected population is seropositive for HBV where approximately 5%-40% individuals are chronically infected. In HIV co-infected individuals, liver-related mortality is estimated over 17 times higher than those with HBV mono-infection. The spectrum of HIV-induced liver diseases includes hepatitis, steatohepatitis, endothelialitis, necrosis, granulomatosis, cirrhosis and carcinoma. Moreover, HIV co-infection significantly alters the natural history of hepatitis B, and therefore complicates the disease management. Though several studies have demonstrated impact of HIV proteins on hepatocyte biology, only a few data is available on interactions between HBV and HIV proteins. Thus, the clinical spectrum as well as the complexity of the co-infection offers challenging fronts to study the underlying molecular mechanisms, and to design effective therapeutic strategies. PMID:25625003

Parvez, Mohammad Khalid

2015-01-27

21

Host Factors and HIV-1 Replication: Clinical Evidence and Potential Therapeutic Approaches  

PubMed Central

HIV and human defense mechanisms have co-evolved to counteract each other. In the process of infection, HIV takes advantage of cellular machinery and blocks the action of the host restriction factors (RF). A small subset of HIV+ individuals control HIV infection and progression to AIDS in the absence of treatment. These individuals known as long-term non-progressors (LNTPs) exhibit genetic and immunological characteristics that confer upon them an efficient resistance to infection and/or disease progression. The identification of some of these host factors led to the development of therapeutic approaches that attempted to mimic the natural control of HIV infection. Some of these approaches are currently being tested in clinical trials. While there are many genes which carry mutations and polymorphisms associated with non-progression, this review will be specifically focused on HIV host RF including both the main chemokine receptors and chemokines as well as intracellular RF including, APOBEC, TRIM, tetherin, and SAMHD1. The understanding of molecular profiles and mechanisms present in LTNPs should provide new insights to control HIV infection and contribute to the development of novel therapies against AIDS. PMID:24167505

Santa-Marta, Mariana; de Brito, Paula Matos; Godinho-Santos, Ana; Goncalves, Joao

2013-01-01

22

Fairy Tales as a Trance Experience: Possible Therapeutic Uses  

Microsoft Academic Search

The psychological literature contains little documentation of the therapeutic use of fairy tales. We suggest that fairy tales are uniquely suitable for hypnotherapy and for helping clients reframe existential issues. We propose that the structure of fairy tales allows the meaning of the story to be applied personally and that they also stimulate unconscious search. We examine the way in

M. Elizabeth Stevens-Guille; Frederic J. Boersma

1992-01-01

23

Optimizing peak bone mass: What are the therapeutic possibilities?  

Microsoft Academic Search

Bone mass in the elderly depends on the rate of involutional bone loss and on the peak bone mass, i.e. the bone mass present around the third decade of life. Factors relating to the attainment of peak bone mass include congenital factors, diet, hormones, physical activity, lifestyle factors, drags and diseases. A therapeutic intervention aimed at increasing peak bone mass

S. Adami

1994-01-01

24

Exosomes as a tumor immune escape mechanism: possible therapeutic implications  

Microsoft Academic Search

Advances in cancer therapy have been substantial in terms of molecular understanding of disease mechanisms, however these advances have not translated into increased survival in the majority of cancer types. One unsolved problem in current cancer therapeutics is the substantial immune suppression seen in patients. Conventionally, investigations in this area have focused on antigen-nonspecific immune suppressive molecules such as cytokines

Thomas E. Ichim; Zhaohui Zhong; Shalesh Kaushal; Xiufen Zheng; Xiubao Ren; Xishan Hao; James A. Joyce; Harold H. Hanley; Neil H. Riordan; James Koropatnick; Vladimir Bogin; Boris R. Minev; Wei-Ping Min; Richard H. Tullis

2008-01-01

25

Interactions of host APOBEC3 restriction factors with HIV-1 in vivo: implications for therapeutics*  

PubMed Central

Restriction factors are natural cellular proteins that defend individual cells from viral infection. These factors include the APOBEC3 family of DNA cytidine deaminases, which restrict the infectivity of HIV-1 by hypermutating viral cDNA and inhibiting reverse transcription and integration. HIV-1 thwarts this restriction activity through its accessory protein virion infectivity factor (Vif), which uses multiple mechanisms to prevent APOBEC3 proteins such as APOBEC3G and APOBEC3F from entering viral particles. Here, we review the basic biology of the interactions between human APOBEC3 proteins and HIV-1 Vif. We also summarize, for the first time, current clinical data on the in vivo effects of APOBEC3 proteins and survey strategies and progress toward developing therapeutics aimed at the APOBEC3-Vif axis. PMID:20096141

Albin, John S.; Harris, Reuben S.

2010-01-01

26

Cytokine production and dysregulation in HIV pathogenesis: Lessons for development of therapeutics and vaccines  

PubMed Central

Numerous studies have characterized the cytokine modulation observed in human immunodeficiency virus (HIV) infected individuals, from initial infection through chronic disease. Progressive and non-progressive HIV infection models show the cytokine milieu differs in terms of production and responsiveness in these two groups, suggesting an understanding of the role cytokines play during infection is necessary for directing the immune response toward viral control. This review will cover cytokine induction and dysfunction during HIV pathogenesis, with a focus on the interplay between cytokines and transcription factors, T cell activation, and exhaustion. We highlight cytokines that have either vaccine adjuvant or therapeutic potential and discuss the need to identify key factors required for prevention of progression, clearance of infection, or protection from acquisition. PMID:22743036

Reuter, Morgan A.; Pombo, Carolina; Betts, Michael R.

2012-01-01

27

Effect of therapeutic HIV recombinant poxvirus vaccines on the size of the resting CD4+ T-cell latent HIV reservoir  

PubMed Central

Objectives Therapeutic HIV vaccinations may alter the size of the resting memory CD4+ T-cell latent HIV reservoir as HIV establishes latency when memory responses are formed, including those toward HIV. Alternatively, latently infected CD4+ T cells maybe killed, while exiting the reservoir upon activation. Methods The effect of therapeutic immunization with modified vaccinia Ankara and Fowlpox-based HIV vaccines on the latent reservoir was examined in 19 young adults who were receiving effective antiretroviral therapy. Correlations between size of the reservoir [measured in infectious units per million (IUPM)] resting CD4+ T cells and HIV-specific immune responses, including immune activation were examined. Decay of the reservoir was assessed using random-effects model. Results A modest transient decrease in the size of the reservoir was observed at week 40 [mean ?0.31 log10 IUPM (95% confidence interval: ?0.60 to ?0.03; P =0.03] following HIV vaccinations. The estimated half-life (T1/2) of the reservoir during the 40 weeks following vaccination was 9.8 months and statistically different from zero (P =0.02), but 35.3 months and not different from zero (P =0.21) over 72 weeks of study. Latent reservoir size at baseline was not correlated with HIV-specific CD4+, CD8+ responses or immune activation, but became correlated with CD4+ IFN? (r =0.54, P =0.02) and IL-2 responses at 6 weeks after immunization (r =0.48, P =0.04). Conclusion Therapeutic HIV vaccinations led to a transient increase in decay of latently infected CD4+ T cells. Further studies of therapeutic HIV vaccines may provide important insights into facilitating decay of the latent reservoir. PMID:21918423

Persaud, Deborah; Luzuriaga, Katherine; Ziemniak, Carrie; Muresan, Petronella; Greenough, Thomas; Fenton, Terry; Blackford, Amanda; Ferguson, Kimberly; Neu, Natalie; Cunningham, Coleen K.

2012-01-01

28

The iron-regulatory hormone hepcidin: a possible therapeutic target?  

PubMed

The maintenance of stable extracellular and intracellular iron concentrations requires the coordinated regulation of iron transport into plasma. Iron is a fundamental cofactor for several enzymes involved in oxidation-reduction reactions. The redox ability of iron can lead to the production of oxygen free radicals, which can damage various cellular components. Therefore, the appropriate regulation of systemic iron homeostasis is decisive in vital processes. Hepcidin has emerged as the central regulatory molecule of systemic iron homeostasis. It is synthesized in hepatocytes and in other cells and released into the circulation. It inhibits the release of iron from enterocytes of the duodenum and from macrophages by binding to the iron exporter protein, ferroportin (FPN). FPN is a transmembrane protein responsible for iron export from cells into the plasma. Hepcidin is internalized with FPN and both are degraded in lysosomes. The hepcidin-FPN axis is the principal regulator of extracellular iron homeostasis in health and disease. Its manipulation via agonists and antagonists is an attractive and novel therapeutic strategy. Hepcidin agonists include compounds that mimic the activity of hepcidin and agents that increase the production of hepcidin by targeting hepcidin-regulatory molecules. The inhibition of hepcidin could be a potentially attractive therapeutic strategy in patients suffering from anaemia or chronic inflammation. In this review, we will summarize the role of hepcidin in iron homeostasis and its contribution to the pathophysiology of inflammation and iron disorders. We will examine emerging new strategies that modulate hepcidin metabolism. PMID:25205158

Rochette, Luc; Gudjoncik, Aurélie; Guenancia, Charles; Zeller, Marianne; Cottin, Yves; Vergely, Catherine

2015-02-01

29

Exosomes as a tumor immune escape mechanism: possible therapeutic implications.  

PubMed

Advances in cancer therapy have been substantial in terms of molecular understanding of disease mechanisms, however these advances have not translated into increased survival in the majority of cancer types. One unsolved problem in current cancer therapeutics is the substantial immune suppression seen in patients. Conventionally, investigations in this area have focused on antigen-nonspecific immune suppressive molecules such as cytokines and T cell apoptosis inducing molecules such as Fas ligand. More recently, studies have demonstrated nanovesicle particles termed exosomes are involved not only in stimulation but also inhibition of immunity in physiological conditions. Interestingly, exosomes secreted by cancer cells have been demonstrated to express tumor antigens, as well as immune suppressive molecules such as PD-1L and FasL. Concentrations of exosomes from plasma of cancer patients have been associated with spontaneous T cell apoptosis, which is associated in some situations with shortened survival. In this paper we place the "exosome-immune suppression" concept in perspective of other tumor immune evasion mechanisms. We conclude by discussing a novel therapeutic approach to cancer immune suppression by extracorporeal removal of exosomes using hollow fiber filtration technology. PMID:18644158

Ichim, Thomas E; Zhong, Zhaohui; Kaushal, Shalesh; Zheng, Xiufen; Ren, Xiubao; Hao, Xishan; Joyce, James A; Hanley, Harold H; Riordan, Neil H; Koropatnick, James; Bogin, Vladimir; Minev, Boris R; Min, Wei-Ping; Tullis, Richard H

2008-01-01

30

Exosomes as a tumor immune escape mechanism: possible therapeutic implications  

PubMed Central

Advances in cancer therapy have been substantial in terms of molecular understanding of disease mechanisms, however these advances have not translated into increased survival in the majority of cancer types. One unsolved problem in current cancer therapeutics is the substantial immune suppression seen in patients. Conventionally, investigations in this area have focused on antigen-nonspecific immune suppressive molecules such as cytokines and T cell apoptosis inducing molecules such as Fas ligand. More recently, studies have demonstrated nanovesicle particles termed exosomes are involved not only in stimulation but also inhibition of immunity in physiological conditions. Interestingly, exosomes secreted by cancer cells have been demonstrated to express tumor antigens, as well as immune suppressive molecules such as PD-1L and FasL. Concentrations of exosomes from plasma of cancer patients have been associated with spontaneous T cell apoptosis, which is associated in some situations with shortened survival. In this paper we place the "exosome-immune suppression" concept in perspective of other tumor immune evasion mechanisms. We conclude by discussing a novel therapeutic approach to cancer immune suppression by extracorporeal removal of exosomes using hollow fiber filtration technology PMID:18644158

Ichim, Thomas E; Zhong, Zhaohui; Kaushal, Shalesh; Zheng, Xiufen; Ren, Xiubao; Hao, Xishan; Joyce, James A; Hanley, Harold H; Riordan, Neil H; Koropatnick, James; Bogin, Vladimir; Minev, Boris R; Min, Wei-Ping; Tullis, Richard H

2008-01-01

31

New diagnostic and therapeutic possibilities for diastolic heart failure  

PubMed Central

Despite the fact that up to half of all heart failure occurs in patients without evidence of systolic cardiac dysfunction, there are no universally accepted diagnostic markers and no approved therapies for heart failure with preserved ejection fraction (HFpEF). HFpEF, otherwise known as diastolic heart failure, has nearly the same grim prognosis as systolic heart failure, and diastolic heart failure is increasing in incidence and prevalence. Major trials have shown that many of the treatments that are salutary in systolic heart failure have no beneficial effects in diastolic heart failure, suggesting different underlying mechanisms for these two disorders. Even criteria for diagnosis of HFpEF are still debated, and there is still no gold standard marker to detect diastolic dysfunction. Here, we will review some promising new insights into the pathogenesis of diastolic dysfunction that may lead to new diagnostic and therapeutic tools. PMID:24494212

Jeong, Euy-Myoung; Dudley, Samuel C.

2014-01-01

32

Enhancement of CCNU cytotoxicity by misonidazole: possible therapeutic gain.  

PubMed Central

Enhancement of CCNU cytotoxicity by misonidazole (MISO) was studied in three tumours and two normal tissues in the mouse. The 3 experimental tumours (SCCVII/St, EMT6 and KHT) showed very different sensitivities to CCNU alone, but MISO enhanced the cell killing in ech case. The effect was not always dose-modifying, so that the CCNU dose range for the greatest enhancement was different in each of the tumours. In all 3 tumours, enhancement increased with dose of MISO. The effect on two normal tissues, marrow (CFU-S) and testis (spermatogonia), was also investigated. Enhancement of marrow toxicity could be demonstrated only at CCNU doses greater than 12.5 mg/kg, so that at lower CCNU doses there was a therapeutic gain equal to the tumour enhancement ratio. The spermatogonia effect, however, showed enhancement by MISO similar to that seen in the tumours at all CCNU doses up to 20 mg/kg. PMID:7201845

Hirst, D. G.; Brown, J. M.; Hazlehurst, J. L.

1982-01-01

33

Possible therapeutic application of GABAB receptor agonists and antagonists.  

PubMed

After their discovery within the mammalian periphery in 1981, gamma-aminobutyric acid-B (GABAB) receptors have been characterized also in the central nervous system (CNS). The highest concentrations of GABAB binding sites appear to be in the cerebellum, frontal cortex, and thalamic nuclei, where they are located on pre- and postsynaptic neurons. On activation, the primary effects appear to be membrane hyperpolarization, suppression of transmitter release, and changes in the levels of cyclic nucleotides. GABAB receptors have been implicated in a variety of neurological phenomena and, as a consequence, receptor agonists and antagonists may well have therapeutic potential. This article is an introduction to GABAB receptor pharmacology and reviews the future of the receptor ligands. Particular attention is given to the role of spinal cord GABAB receptors in chronic pain. PMID:8665542

Malcangio, M; Bowery, N G

1995-08-01

34

[Probiotics: from Metchnikoff to the current preventive and therapeutic possibilities].  

PubMed

About a century ago, Metchnikoff first hypothesised that some intestinal bacteria "produce compounds useful against a premature ageing". Since then, studies progressed over last century, leading to a remarkable improvement of the knowledge about the role of intestinal micro-organisms. Nowadays a number of different micro-organisms satisfying certain requisites are named probiotics and are produced on a large scale. At present, a rational use of probiotics with preventive and therapeutic purposes has been proposed not only for some gastrointestinal pathologies, such as the infective diarrhea (as recommended by the Italian Society of Pediatric, the Italian Society of Gastroenterology and Hepatology, the Italian Society of Pediatric Infectious Disease, and by International Societies), but also for other pathologic conditions, such as the atopic dermatitis and related affections (as suggested by the American Academy of Dermatology Association guide lines). Moreover, the use of probiotics is going to be extended to other pathologies, such as the inflammatory intestinal and respiratory diseases, and even to the prevention of tooth decay, although the actual preventive and therapeutic effects of probiotics onto these pathologies have to be carefully investigated. It is unknown if the genius Leonardo Da Vinci (1452-1519), stating that "man's life is built up by food" imagined how nutrients can influence human health, besides being essential for life, as it is today increasingly evident. Avoiding an excessive optimism and the thought that an efficacious panacea for all troubles has been found, there are sound reasons to believe that probiotics, and prebiotics as well, can influence human health, through the prevention and therapy of many diseases, although further studies are still requested to fully clarify the mechanisms of action of these micro-organisms on each pathology. PMID:15529809

Caramia, G

2004-01-01

35

Indian Herbal Medicines: Possible Potent Therapeutic Agents for Rheumatoid Arthritis  

PubMed Central

Rheumatoid arthritis (RA) is an autoimmune disease of unknown etiology and is mainly characterized by the progressive erosion of cartilage leading to chronic polyarthritis and joint distortion. Although the exact pathogenesis of the disease has yet not been elucidated, however, studies suggest that cellular proliferation of synoviocytes result in pannus formation which damages the cartilage and bone. Recent reports also support the role of free radicals in its pathogenesis. Apart from the conventional treatment strategies using nonsteroidal anti-inflammatory drugs, disease modifying antirheumatic drugs and glucocorticoids, newer and safer drugs are continuously being searched, as long term usage of these drugs have resulted in adverse effects. Alternative medicine provides another approach for treatment of RA and currently a number of medicinal plants are under scientific evaluation to develop a novel drug. There is a dire need to investigate the complete therapeutic potential and adverse effects, if any, of these herbals for providing newer and safer treatment options with minimum side effects. In this review we have tried to explore various Indian ancient Ayurvedic, Unani and Tibbi, as also some Chinese and Korean, herbals for their potential to treat RA. PMID:18392103

Rathore, Brijesh; Ali Mahdi, Abbas; Nath Paul, Bhola; Narayan Saxena, Prabhu; Kumar Das, Siddharth

2007-01-01

36

HIV-1 Latency: An Update of Molecular Mechanisms and Therapeutic Strategies  

PubMed Central

The major obstacle towards HIV-1 eradication is the life-long persistence of the virus in reservoirs of latently infected cells. In these cells the proviral DNA is integrated in the host’s genome but it does not actively replicate, becoming invisible to the host immune system and unaffected by existing antiviral drugs. Rebound of viremia and recovery of systemic infection that follows interruption of therapy, necessitates life-long treatments with problems of compliance, toxicity, and untenable costs, especially in developing countries where the infection hits worst. Extensive research efforts have led to the proposal and preliminary testing of several anti-latency compounds, however, overall, eradication strategies have had, so far, limited clinical success while posing several risks for patients. This review will briefly summarize the more recent advances in the elucidation of mechanisms that regulates the establishment/maintenance of latency and therapeutic strategies currently under evaluation in order to eradicate HIV persistence. PMID:24736215

Battistini, Angela; Sgarbanti, Marco

2014-01-01

37

[Extrahepatic cholestasis of nonatretic origin. New diagnostic and therapeutic possibilities].  

PubMed

Nonatretic cholestatic disorders exhibit differential features in the pediatric age group, at times not too obvious but always discernible. These characteristic differences, with the aid of increasingly more precise exploratory techniques, make a rapid and sound diagnosis possible. At present, echography, transparietohepatic cholangiography and endoscopic retrograde cholangiography allow us, within a short time, to reach a diagnosis of disorders that not long ago were only roughly profiled and on occasion were left undiagnosed. At the Children's Hospital Valle de Hebrón, treatment has been afforded, in the last seven years, to seven patients with a choledochal cyst, four with a long common biliopancreatic duct, one with a choleperitoneum due to spontaneous perforation of a choledochal cyst and one patient with congenital stenosis of the common hepatic duct. In all cases where echography was performed, an intra- or extrahepatic bile duct dilatation could be demonstrated, or otherwise the diagnosis of a choledochal cyst was established. Furthermore, four transhepatic and three retrograde cholangiographic examinations were carried out, via a fiber duodenoscopy, in those cases that failed to show, on echography, the existence of a choledochal cyst. PMID:2076365

Broto, J; Marhuenda, C; Casasa, J M; Gil Vernet, J M; Pérez, A; Boix Ochoa, J

1990-10-01

38

Therapeutic applications of the cell-penetrating HIV-1 Tat peptide.  

PubMed

Over the past decades, many new therapeutic approaches have been developed for several conditions, including neurodegenerative diseases. However, efficient biodistribution and delivery at biological target sites are hampered by the presence of cell and tissue barriers, and a clinical therapy is prevented by the requirement of invasive administration routes. Candidate drug conjugation to cell-penetrating peptides, which are able to cross cellular membranes and reach biological targets even when administered systemically, represents a promising tool to overcome this issue. Here, we review the biology, classification and mechanisms of internalization of cell-penetrating peptides. We focus our attention on the cell-penetrating peptide: HIV-derived Tat peptide, and discuss its efficient but controversial use in basic, preclinical and clinical research from its discovery to the present day. PMID:25277319

Rizzuti, Mafalda; Nizzardo, Monica; Zanetta, Chiara; Ramirez, Agnese; Corti, Stefania

2015-01-01

39

Therapeutic Vaccination Expands and Improves the Function of the HIV-Specific Memory T-Cell Repertoire  

PubMed Central

Background.?The licensing of herpes zoster vaccine has demonstrated that therapeutic vaccination can help control chronic viral infection. Unfortunately, human trials of immunodeficiency virus (HIV) vaccine have shown only marginal efficacy. Methods.?In this double-blind study, 17 HIV-infected individuals with viral loads of <50 copies/mL and CD4+ T-cell counts of >350 cells/µL were randomly assigned to the vaccine or placebo arm. Vaccine recipients received 3 intramuscular injections of HIV DNA (4 mg) coding for clade B Gag, Pol, and Nef and clade A, B, and C Env, followed by a replication-deficient adenovirus type 5 boost (1010 particle units) encoding all DNA vaccine antigens except Nef. Humoral, total T-cell, and CD8+ cytotoxic T-lymphocyte (CTL) responses were studied before and after vaccination. Single-copy viral loads and frequencies of latently infected CD4+ T cells were determined. Results.?Vaccination was safe and well tolerated. Significantly stronger HIV-specific T-cell responses against Gag, Pol, and Env, with increased polyfunctionality and a broadened epitope-specific CTL repertoire, were observed after vaccination. No changes in single-copy viral load or the frequency of latent infection were observed. Conclusions.?Vaccination of individuals with existing HIV-specific immunity improved the magnitude, breadth, and polyfunctionality of HIV-specific memory T-cell responses but did not impact markers of viral control. Clinical Trials Registration.?NCT00270465 PMID:23482645

Casazza, Joseph P.; Bowman, Kathryn A.; Adzaku, Selorm; Smith, Emily C.; Enama, Mary E.; Bailer, Robert T.; Price, David A.; Gostick, Emma; Gordon, Ingelise J.; Ambrozak, David R.; Nason, Martha C.; Roederer, Mario; Andrews, Charla A.; Maldarelli, Frank M.; Wiegand, Ann; Kearney, Mary F.; Persaud, Deborah; Ziemniak, Carrie; Gottardo, Raphael; Ledgerwood, Julie E.; Graham, Barney S.; Koup, Richard A.

2013-01-01

40

Epigenetic Modulations in Activated Cells Early after HIV-1 Infection and Their Possible Functional Consequences  

PubMed Central

Epigenetic modifications refer to a number of biological processes which alter the structure of chromatin and its transcriptional activity such as DNA methylation and histone post-translational processing. Studies have tried to elucidate how the viral genome and its products are affected by epigenetic modifications imposed by cell machinery and how it affects the ability of the virus to either, replicate and produce a viable progeny or be driven to latency. The purpose of this study was to evaluate epigenetic modifications in PBMCs and CD4+ cells after HIV-1 infection analyzing three approaches: (i) global DNA- methylation; (ii) qPCR array and (iii) western blot. HIV-1 infection led to methylation increases in the cellular DNA regardless the activation status of PBMCs. The analysis of H3K9me3 and H3K27me3 suggested a trend towards transcriptional repression in activated cells after HIV-1 infection. Using a qPCR array, we detected genes related to epigenetic processes highly modulated in activated HIV-1 infected cells. SETDB2 and RSK2 transcripts showed highest up-regulation levels. SETDB2 signaling is related to transcriptional silencing while RSK2 is related to either silencing or activation of gene expression depending on the signaling pathway triggered down-stream. In addition, activated cells infected by HIV-1 showed lower CD69 expression and a decrease of IL-2, IFN-? and metabolism-related factors transcripts indicating a possible functional consequence towards global transcriptional repression found in HIV-1 infected cells. Conversely, based on epigenetic markers studied here, non-stimulated cells infected by HIV-1, showed signs of global transcriptional activation. Our results suggest that HIV-1 infection exerts epigenetic modulations in activated cells that may lead these cells to transcriptional repression with important functional consequences. Moreover, non-stimulated cells seem to increase gene transcription after HIV-1 infection. Based on these observations, it is possible to speculate that the outcome of viral infections may be influenced by the cellular activation status at the moment of infection. PMID:25875202

Maricato, Juliana T.; Furtado, Maria N.; Takenaka, Maisa C.; Nunes, Edsel R. M.; Fincatti, Patricia; Meliso, Fabiana M.; da Silva, Ismael D. C. G.; Jasiulionis, Miriam G.; Cecília de Araripe Sucupira, Maria; Diaz, Ricardo Sobhie; Janini, Luiz M. R.

2015-01-01

41

A randomized therapeutic vaccine trial of canarypox-HIV-pulsed dendritic cells vs. canarypox-HIV alone in HIV-1-infected patients on antiretroviral therapy?,??  

PubMed Central

Targeting canarypox (CP)-HIV vaccine to dendritic cells (DCs) elicits anti-HIV-1 immune responses in vitro. We conducted a phase I/II clinical trial to evaluate whether adding DC to a CP-HIV vaccine improved virologic control during analytic treatment interruption (ATI) in HIV-1-infected subjects. Twenty-nine subjects on suppressive antiretroviral therapy were randomized to vaccination with autologous DCs infected with CP-HIV + keyhole limpet hemocyanin (KLH) (arm A, n = 14) or CP-HIV + KLH alone (arm B, n = 15). The mean viral load (VL) setpoint during ATI did not differ between subjects in arms A and B. A higher percentage of subjects in the DC group had a VL setpoint <5000 c/mL during ATI (4/13 or 31% in arm A compared with 0/13 in arm B, p = 0.096), but virologic control was transient. Subjects in arm A had a greater increase in KLH lymphoproliferative response than subjects in arm B; however, summed ELISPOT responses to HIV-1 antigens did not differ by treatment arm. We conclude that a DC-CP-HIV vaccine is well-tolerated in HIV-1-infected patients, but does not lower VL setpoint during ATI compared with CP-HIV alone. New methods to enhance the immunogenicity and antiviral efficacy of DC-based vaccines for HIV-1 infection are needed. PMID:19450647

Gandhi, Rajesh T.; O'Neill, David; Bosch, Ronald J.; Chan, Ellen S.; Bucy, R. Pat; Shopis, Janet; Baglyos, Lynn; Adams, Elizabeth; Fox, Lawrence; Purdue, Lynette; Marshak, Ann; Flynn, Theresa; Masih, Reena; Schock, Barbara; Mildvan, Donna; Schlesinger, Sarah J.; Marovich, Mary A.; Bhardwaj, Nina; Jacobson, Jeffrey M.

2010-01-01

42

The Role of Chemokines in Breast Cancer Pathology and Its Possible Use as Therapeutic Targets  

PubMed Central

Chemokines are small proteins that primarily regulate the traffic of leukocytes under homeostatic conditions and during specific immune responses. The chemokine-chemokine receptor system comprises almost 50 chemokines and approximately 20 chemokine receptors; thus, there is no unique ligand for each receptor and the binding of different chemokines to the same receptor might have disparate effects. Complicating the system further, these effects depend on the cellular milieu. In cancer, although chemokines are associated primarily with the generation of a protumoral microenvironment and organ-directed metastasis, they also mediate other phenomena related to disease progression, such as angiogenesis and even chemoresistance. Therefore, the chemokine system is becoming a target in cancer therapeutics. We review the emerging data and correlations between chemokines/chemokine receptors and breast cancer, their implications in cancer progression, and possible therapeutic strategies that exploit the chemokine system. PMID:25165728

Palacios-Arreola, M. Isabel; Nava-Castro, Karen E.; Castro, Julieta I.; García-Zepeda, Eduardo; Carrero, Julio C.; Morales-Montor, Jorge

2014-01-01

43

Endotoxin release in cardiac surgery with cardiopulmonary bypass: pathophysiology and possible therapeutic strategies. An update.  

PubMed

Cardiac surgery with cardiopulmonary bypass provokes a systemic inflammatory response syndrome caused by the surgical trauma itself, blood contact with the non-physiological surfaces of the extracorporeal circuit, endotoxemia, and ischemia. The role of endotoxin in the inflammatory response syndrome has been well investigated. In this report, we reviewed recent advances in the understanding of the pathophysiology of the endotoxin release during cardiopulmonary bypass and the possible therapeutic strategies aimed to reduce the endotoxin release or to counteract the inflammatory effects of endotoxin. Although many different strategies to detoxify endotoxins were evaluated, none of them were able to show statistically significant differences in clinical outcome. PMID:20663682

Kats, Suzanne; Schönberger, Jacques P A M; Brands, Ruud; Seinen, Willem; van Oeveren, Wim

2011-04-01

44

Bone-derived mesenchymal stromal cells from HIV transgenic mice exhibit altered proliferation, differentiation capacity and paracrine functions along with impaired therapeutic potential in kidney injury  

SciTech Connect

Mesenchymal stem cells (MSCs) secrete paracrine factors that could be cytoprotective and serve roles in immunoregulation during tissue injury. Although MSCs express HIV receptors, and co-receptors, and are susceptible to HIV infection, whether HIV-1 may affect biological properties of MSCs needs more study. We evaluated cellular proliferation, differentiation and paracrine functions of MSCs isolated from compact bones of healthy control mice and Tg26 HIV-1 transgenic mice. The ability of MSCs to protect against cisplatin toxicity was studied in cultured renal tubular cells as well as in intact mice. We successfully isolated MSCs from healthy mice and Tg26 HIV-1 transgenic mice and found the latter expressed viral Nef, Vpu, NL4-3 and Vif genes. The proliferation and differentiation of Tg26 HIV-1 MSCs was inferior to MSCs from healthy mice. Moreover, transplantation of Tg26 HIV-1 MSCs less effectively improved outcomes compared with healthy MSCs in mice with acute kidney injury. Also, Tg26 HIV-1 MSCs secreted multiple cytokines, but at significantly lower levels than healthy MSCs, which resulted in failure of conditioned medium from these MSCs to protect cultured renal tubular cells from cisplatin toxicity. Therefore, HIV-1 had adverse biological effects on MSCs extending to their proliferation, differentiation, function, and therapeutic potential. These findings will help in advancing mechanistical insight in renal injury and repair in the setting of HIV-1 infection. -- Highlights: •MSCs isolated from HIV mice displayed HIV genes. •MSCs isolated from HIV mice exhibited attenuated growth and paracrine functions. •AKI mice with transplanted HIV-MSC displayed poor outcome. •HIV-1 MSC secreted multiple cytokines but at a lower level.

Cheng, Kang; Rai, Partab; Lan, Xiqian; Plagov, Andrei; Malhotra, Ashwani [Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System, Manhassett, NY (United States); Gupta, Sanjeev [Departments of Medicine and Pathology, Marion Bessin Liver Research Center, Diabetes Center, Cancer Center, Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research, Institute for Clinical and Translational Research, Albert Einstein College of Medicine, Bronx, NY (United States); Singhal, Pravin C., E-mail: psinghal@nshs.edu [Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System, Manhassett, NY (United States)

2013-08-15

45

Understanding HIV Latency: The Road to an HIV Cure  

PubMed Central

Treatment with antiretroviral therapy dramatically increases the survival of HIV-infected individuals. However, treatment has to be continued for life because it does not lead to the full eradication of infection. HIV persists in resting CD4+ T cells, and possibly other cell types, and can reemerge from these cells when therapy is interrupted. Here, we review molecular mechanisms that have been proposed to contribute to HIV latency, as well as the relative roles of cis- and trans-acting mechanisms. We also discuss existing and future therapeutic opportunities regarding HIV latency that might lead to a future cure for HIV infection. PMID:25587657

Dahabieh, Matthew; Battivelli, Emilie; Verdin, Eric

2015-01-01

46

The Use of Therapeutic Drug Monitoring in Complex Antituberculous and Antiretroviral Drug Dosing in HIV-Tuberculosis Coinfected Patients.  

PubMed

We report 2 cases coinfected with HIV and tuberculosis (HIV-TB), requiring drug dose adjustments guided by therapeutic drug monitoring (TDM) and/or serum drug concentrations. CASE 1: Over the course of the 9-months of TB treatment, drugs that required increased doses due to low concentrations included efavirenz (800 mg), rifampin (900 mg), and isoniazid (450 mg). Higher drug doses were well tolerated until the end of treatment. CASE 2: Over the 12-month course of TB therapy, drugs that required increased doses due to incomplete and/or delayed absorption were rifampin (1500 mg), moxifloxacin (800 mg), and ethambutol (1600 mg). Higher drug doses were well tolerated until the end of treatment. Due to delayed/incomplete drug absorption and weight gain during therapy, higher antituberculous doses may be required in patients coinfected with HIV-TB. A daily dose of efavirenz 800 mg was well tolerated in both patients (weight over 70 kg). Managing patients coinfected with HIV-TB is complex, and, therefore, TDM of drug concentrations can help guide clinical decision making. PMID:25425639

Newman, Michael; Foisy, Michelle M; Ahmed, Rabia A

2014-11-25

47

Aging and HIV/AIDS: pathogenetic role of therapeutic side effects  

PubMed Central

The intersection of aging and HIV/AIDS is a looming ‘epidemic within an epidemic.’ This paper reviews how HIV/AIDS and its therapy cause premature aging or contribute mechanistically to HIV-associated non-AIDS illnesses (HANA). Survival with HIV/AIDS has markedly improved by therapy combinations containing nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors, and protease inhibitors (PIs) called HAART (highly active anti-retroviral therapy). Because NRTIs and PIs together prevent or attenuate HIV-1 replication, and prolong life, the population of aging patients with HIV/AIDS increases accordingly. However, illnesses frequently associated with aging in the absence of HIV/AIDS appear to occur prematurely in HIV/AIDS patients. Theories that help to explain biological aging include oxidative stress (where mitochondrial oxidative injury exceeds antioxidant defense), chromosome telomere shortening with associated cellular senescence, and accumulation of lamin A precursors (a nuclear envelop protein). Each of these has the potential to be enhanced or caused by HIV/AIDS, antiretroviral therapy, or both. Antiretroviral therapy has been shown to enhance events seen in biological aging. Specifically, antiretroviral NRTIs cause mitochondrial dysfunction, oxidative stress, and mitochondrial DNA defects that resemble features of both HANA and aging. More recent clinical evidence points to telomere shortening caused by NRTI triphosphate-induced inhibition of telomerase, suggesting telomerase reverse transcriptase (TERT) inhibition as being a pathogenetic contributor to premature aging in HIV/AIDS. PIs may also have a role in premature aging in HIV/AIDS as they cause prelamin A accumulation. Overall, toxic side effects of HAART may both resemble and promote events of aging and are worthy of mechanistic studies. PMID:24336070

Torres, Rebecca A; Lewis, William

2014-01-01

48

Cytotoxic and Cytolytic Cnidarian Venoms. A Review on Health Implications and Possible Therapeutic Applications  

PubMed Central

The toxicity of Cnidaria is a subject of concern for its influence on human activities and public health. During the last decades, the mechanisms of cell injury caused by cnidarian venoms have been studied utilizing extracts from several Cnidaria that have been tested in order to evaluate some fundamental parameters, such as the activity on cell survival, functioning and metabolism, and to improve the knowledge about the mechanisms of action of these compounds. In agreement with the modern tendency aimed to avoid the utilization of living animals in the experiments and to substitute them with in vitro systems, established cell lines or primary cultures have been employed to test cnidarian extracts or derivatives. Several cnidarian venoms have been found to have cytotoxic properties and have been also shown to cause hemolytic effects. Some studied substances have been shown to affect tumour cells and microorganisms, so making cnidarian extracts particularly interesting for their possible therapeutic employment. The review aims to emphasize the up-to-date knowledge about this subject taking in consideration the importance of such venoms in human pathology, the health implications and the possible therapeutic application of these natural compounds. PMID:24379089

Mariottini, Gian Luigi; Pane, Luigi

2013-01-01

49

Sang Froid in a time of trouble: is a vaccine against HIV possible?  

PubMed Central

Since the announcement of the STEP trial results in the past months, we have heard many sober pronouncements on the possibility of an HIV vaccine. On the other hand, optimistic quotations have been liberally used, from Shakespeare's Henry V's "Once more unto the breach, dear friends" to Winston Churchill's definition of success as "going from one failure to another with no loss of enthusiasm". I will forgo optimistic quotations for the phrase "Sang Froid", which translates literally from the French as "cold blood"; what it really means is to avoid panic when things look bad, to step back and coolly evaluate the situation. This is not to counsel easy optimism or to fly in face of the facts, but I believe that while the situation is serious, it is not desperate. I should stipulate at the outset that I am neither an immunologist nor an expert in HIV, but someone who has spent his life in vaccine development. What I will try to do is to provide a point of view from that experience. There is no doubt that the results of STEP were disappointing: not only did the vaccine fail to control viral load, but may have adversely affected susceptibility to infection. But HIV is not the only vaccine to experience difficulties; what lessons can we glean from prior vaccine development? PMID:19187552

2009-01-01

50

Relevance and Therapeutic Possibility of PTEN-Long in Renal Cell Carcinoma  

PubMed Central

PTEN-Long is a translational variant of PTEN (Phosphatase and Tensin Homolog). Like PTEN, PTEN-Long is able to antagonize the PI3K-Akt pathway and inhibits tumor growth. In this study, we investigated the role PTEN-Long plays in the development and progression of clear cell renal cell carcinoma (ccRCC) and explored the therapeutic possibility using proteinaceous PTEN-Long to treat ccRCC. We found that the protein levels of PTEN-Long were drastically reduced in ccRCC, which was correlated with increased levels of phosphorylated Akt (pAkt). Gain of function experiments showed overexpression of PTEN-Long in the ccRCC cell line 786-0 suppressed PI3K-Akt signaling, inhibited cell proliferation, migration and invasion, and eventually induced cell death. When purified PTEN-Long was added into cultured 786-0 cells, it entered cells, blocked Akt activation, and induced apoptosis involving Caspase 3 cleavage. Furthermore, PTEN-Long inhibited proliferation of 786-0 cells in xenograft mouse model. Our results implicated that understanding the roles of PTEN-Long in renal cell carcinogenesis has therapeutic significance. PMID:25714556

Lin, Chunhua; Yu, Qingxia; Wu, Jitao; Wang, Lin; Cui, Yupeng; Wang, Ke; Gao, Zhenli; Li, Hong

2015-01-01

51

Relevance and Therapeutic Possibility of PTEN-Long in Renal Cell Carcinoma.  

PubMed

PTEN-Long is a translational variant of PTEN (Phosphatase and Tensin Homolog). Like PTEN, PTEN-Long is able to antagonize the PI3K-Akt pathway and inhibits tumor growth. In this study, we investigated the role PTEN-Long plays in the development and progression of clear cell renal cell carcinoma (ccRCC) and explored the therapeutic possibility using proteinaceous PTEN-Long to treat ccRCC. We found that the protein levels of PTEN-Long were drastically reduced in ccRCC, which was correlated with increased levels of phosphorylated Akt (pAkt). Gain of function experiments showed overexpression of PTEN-Long in the ccRCC cell line 786-0 suppressed PI3K-Akt signaling, inhibited cell proliferation, migration and invasion, and eventually induced cell death. When purified PTEN-Long was added into cultured 786-0 cells, it entered cells, blocked Akt activation, and induced apoptosis involving Caspase 3 cleavage. Furthermore, PTEN-Long inhibited proliferation of 786-0 cells in xenograft mouse model. Our results implicated that understanding the roles of PTEN-Long in renal cell carcinogenesis has therapeutic significance. PMID:25714556

Wang, Hui; Zhang, Peng; Lin, Chunhua; Yu, Qingxia; Wu, Jitao; Wang, Lin; Cui, Yupeng; Wang, Ke; Gao, Zhenli; Li, Hong

2015-01-01

52

Brief report Therapeutic levels of human factor VIII and IX using HIV-1based  

E-print Network

an important role in hemophilia gene therapy. The present study used human immunodeficiency virus (HIV Gene therapy for hemophilia has been targeted to the liver because it is the normal site of factor VIII

Kay, Mark A.

53

HIV\\/HCV Co-infection: Pathogenesis, Clinical Complications, Treatment, and New Therapeutic Technologies  

Microsoft Academic Search

World-wide, hepatitis C virus (HCV) accounts for approximately 130 million chronic infections, with an overall 3% prevalence.\\u000a Four to 5 million persons are co-infected with HIV. It is well established that HIV has a negative impact on the natural history\\u000a of HCV, including a higher rate of viral persistence, increased viral load, and more rapid progression to fibrosis, end-stage\\u000a liver

Eva A. Operskalski; Andrea Kovacs

2011-01-01

54

Complex DNA repair pathways as possible therapeutic targets to overcome temozolomide resistance in glioblastoma  

PubMed Central

Many conventional chemotherapeutic drugs exert their cytotoxic function by inducing DNA damage in the tumor cell. Therefore, a cell-inherent DNA repair pathway, which reverses the DNA-damaging effect of the cytotoxic drugs, can mediate therapeutic resistance to chemotherapy. The monofunctional DNA-alkylating agent temozolomide (TMZ) is a commonly used chemotherapeutic drug and the gold standard treatment for glioblastoma (GBM). Although the activity of DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT) has been described as the main modulator to determine the sensitivity of GBM to TMZ, a subset of GBM does not respond despite MGMT inactivation, suggesting that another DNA repair mechanism may also modulate the tolerance to TMZ. Considerable interest has focused on MGMT, mismatch repair (MMR), and the base excision repair (BER) pathway in the mechanism of mediating TMZ resistance, but emerging roles for the DNA strand-break repair pathway have been demonstrated. In the first part of this review article, we briefly review the significant role of MGMT, MMR, and the BER pathway in the tolerance to TMZ; in the last part, we review the recent publications that demonstrate possible roles of DNA strand-break repair pathways, such as single-strand break repair and double-strand break repair, as well as the Fanconi anemia pathway in the repair process after alkylating agent-based therapy. It is possible that all of these repair pathways have a potential to modulate the sensitivity to TMZ and aid in overcoming the therapeutic resistance in the clinic. PMID:23227453

Yoshimoto, Koji; Mizoguchi, Masahiro; Hata, Nobuhiro; Murata, Hideki; Hatae, Ryusuke; Amano, Toshiyuki; Nakamizo, Akira; Sasaki, Tomio

2012-01-01

55

Nutrition outcomes of HIV-infected malnourished adults treated with ready-to-use therapeutic food in sub-Saharan Africa: a longitudinal study  

Microsoft Academic Search

BACKGROUND: Among people living with HIV\\/AIDS, nutritional support is increasingly recognized as a critical part of the essential package of care, especially for patients in sub-Saharan Africa. The objectives of the study were to evaluate the outcomes of HIV-positive malnourished adults treated with ready-to-use therapeutic food and to identify factors associated with nutrition programme failure. METHODS: We present results from

Laurence Ahoua; Chantal Umutoni; Helena Huerga; Andrea Minetti; Elisabeth Szumilin; Suna Balkan; David M Olson; Sarala Nicholas; Mar Pujades-Rodríguez

2011-01-01

56

Possible Biomarkers for the Early Detection of HIV-associated Heart Diseases: A Proteomics and Bioinformatics Prediction  

PubMed Central

The frequency of cardiovascular disorders is increasing in HIV-infected individuals despite a significant reduction in the viral load by antiretroviral therapies (ART). Since the CD4 + T-cells are responsible for the viral load as well as immunological responses, we hypothesized that chronic HIV-infection of T-cells produces novel proteins/enzymes that cause cardiac dysfunctions. To identify specific factors that might cause cardiac disorders without the influence of numerous cofactors produced by other pathogenic microorganisms that co-inhabit most HIV-infected individuals, we analyzed genome-wide proteomes of a CD4 + T-cell line at different stages of HIV replication and cell growth over > 6 months. Subtractive analyses of several hundred differentially regulated proteins from HIV-infected and uninfected counterpart cells and comparisons with proteins expressed from the same cells after treating with the antiviral drug Zidovudine/AZT and inhibiting virus replication, identified a well-coordinated network of 12 soluble/diffusible proteins in HIV-infected cells. Functional categorization, bioinformatics and statistical analyses of each protein predicted that the expression of cardiac-specific Ca2 + kinase together with multiple Ca2 + release channels causes a sustained overload of Ca2 + in the heart which induces fetal/cardiac myosin heavy chains (MYH6 and MYH7) and a myosin light-chain kinase. Each of these proteins has been shown to cause cardiac stress, arrhythmia, hypertrophic signaling, cardiomyopathy and heart failure (p = 8 × 10? 11). Translational studies using the newly discovered proteins produced by HIV infection alone would provide additional biomarkers that could be added to the conventional markers for an early diagnosis and/or development of specific therapeutic interventions for heart diseases in HIV-infected individuals.

Rasheed, Suraiya; Hashim, Rahim; Yan, Jasper S.

2015-01-01

57

Antiviral peptide nanocomplexes as a potential antiviral therapeutic modality for HIV/HCV co-infection  

PubMed Central

It is estimated that 4 to 5 million people are currently co-infected with Human Immunodeficiency Virus (HIV) and Hepatitis C Virus (HCV). HIV/HCV co-infection is associated with unique health risks including increased hepatotoxicity of antiretrovirals, accelerated progression of HCV and liver diseases. The standard interferon-based therapy is effective only in about 50% of patients and often is associated with autoimmune and neuro-psychiatric complications. The treatment of co-infection (HIV/HCV) requires new strategic approaches. To this end, the formulations of an amphiphatic ?-helical peptide, a positively charged analog of C5A peptide derived from the HCV NS5A protein, with a reported virocidal activity were prepared by electrostatic coupling with anionic poly(amino acid)-based block copolymers. The self-assembled antiviral peptide nanocomplexes (APN) were ca. 35 nm in size, stable at physiological pH and ionic strength, and retained in vitro antiviral activity against HCV and HIV. Moreover, incorporation of the peptide into APN attenuated its cytotoxicity associated with the positive charge. In vivo APN were able to decrease the viral load in mice transplanted with human lymphocytes and HIV-1-infected. Overall, these findings indicate the potential of these formulations for stabilization and delivery of antiviral peptides while maintaining their functional activity. PMID:23403120

Zhang, Jingjin; Mulvenon, Andrea; Makarov, Edward; Wagoner, Jill; Knibbe, Jaclyn; Kim, Jong Oh; Osna, Natalia

2013-01-01

58

Human Immunodeficiency Virus-1 (HIV-1)-Mediated Apoptosis: New Therapeutic Targets  

PubMed Central

HIV has posed a significant challenge due to the ability of the virus to both impair and evade the host’s immune system. One of the most important mechanisms it has employed to do so is the modulation of the host’s native apoptotic pathways and mechanisms. Viral proteins alter normal apoptotic signaling resulting in increased viral load and the formation of viral reservoirs which ultimately increase infectivity. Both the host’s pro- and anti-apoptotic responses are regulated by the interactions of viral proteins with cell surface receptors or apoptotic pathway components. This dynamic has led to the development of therapies aimed at altering the ability of the virus to modulate apoptotic pathways. These therapies are aimed at preventing or inhibiting viral infection, or treating viral associated pathologies. These drugs target both the viral proteins and the apoptotic pathways of the host. This review will examine the cell types targeted by HIV, the surface receptors exploited by the virus and the mechanisms whereby HIV encoded proteins influence the apoptotic pathways. The viral manipulation of the hosts’ cell type to evade the immune system, establish viral reservoirs and enhance viral proliferation will be reviewed. The pathologies associated with the ability of HIV to alter apoptotic signaling and the drugs and therapies currently under development that target the ability of apoptotic signaling within HIV infection will also be discussed. PMID:25196285

Mbita, Zukile; Hull, Rodney; Dlamini, Zodwa

2014-01-01

59

Uptake of HIV testing and outcomes within a Community-based Therapeutic Care (CTC) programme to treat Severe Acute Malnutrition in Malawi: a descriptive study  

PubMed Central

Background In Malawi and other high HIV prevalence countries, studies suggest that more than 30% of all severely malnourished children admitted to inpatient nutrition rehabilitation units are HIV-infected. However, clinical algorithms designed to diagnose paediatric HIV are neither sensitive nor specific in severely malnourished children. The present study was conducted to assess : i) whether HIV testing can be integrated into Community-based Therapeutic Care (CTC); ii) to determine if CTC can improve the identification of HIV infected children; and iii) to assess the impact of CTC programmes on the rehabilitation of HIV-infected children with Severe Acute Malnutrition (SAM). Methods This community-based cohort study was conducted in Dowa District, Central Malawi, a rural area 50 km from the capital, Lilongwe. Caregivers and children admitted in the Dowa CTC programme were prospectively (Prospective Cohort = PC) and retrospectively (Retrospective Cohort = RC) admitted into the study and offered HIV testing and counseling. Basic medical care and community nutrition rehabilitation was provided for children with SAM. The outcomes of interest were uptake of HIV testing, and recovery, relapse, and growth rates of HIV-positive and uninfected children in the CTC programme. Student's t-test and analysis of variance were used to compare means and Kruskall Wallis tests were used to compare medians. Dichotomous variables were compared using Chi2 analyses and Fisher's exact test. Stepwise logistic regression with backward elimination was used to identify predictors of HIV infection (? = 0.05). Results 1273 and 735 children were enrolled in the RC and PC. For the RC, the average age (SD) at CTC admission was 30.0 (17.2) months. For the PC, the average age at admission was 26.5 (13.7) months. Overall uptake of HIV testing was 60.7% for parents and 94% for children. HIV prevalence in severely malnourished children was 3%, much lower than anticipated. 59% of HIV-positive and 83% of HIV-negative children achieved discharge Weight-For-Height (WFH) ? 80% of the NCHS reference median (p = 0.003). Clinical algorithms for diagnosing HIV in SAM children had poor sensitivity and specificity. Conclusion CTC is a potentially valuable entry point for providing HIV testing and care in the community to HIV infected children with SAM. PMID:18671876

Bahwere, Paluku; Piwoz, Ellen; Joshua, Marthias C; Sadler, Kate; Grobler-Tanner, Caroline H; Guerrero, Saul; Collins, Steve

2008-01-01

60

Lower HIV prevalence among Asian/Pacific Islander men who have sex with men: a critical review for possible reasons.  

PubMed

We conducted a critical literature review for possible reasons that may explain the lower HIV prevalence observed among API MSM compared to MSM of other races/ethnicities. Trends emerging from the literature suggest that traditional individual-level factors-unprotected anal intercourse, substance use, STD prevalence, rates and frequency of HIV testing, and utilization of HIV prevention services-do not appear to be related to the lower HIV prevalence among API MSM. Some evidence suggests that socio-cultural and structural factors might be the more critical forces in determining racial/ethnic disparities of HIV among MSM. For API MSM, these factors include structures of sexual networks, access to and reception of medical care and treatment among HIV-positive MSM, and influences of different levels and types of acculturation. Moreover, emerging risk reduction strategies, such as seroadaptive behaviors, could play a role. Future research should address these factors in intervention design. In addition, better theories of resilience and measurement of strengths and protective factors are needed to enhance the efficacy of HIV interventions. PMID:21153049

Wei, Chongyi; Raymond, H Fisher; Wong, Frank Y; Silvestre, Anthony J; Friedman, Mark S; Documét, Patricia; McFarland, Willi; Stall, Ron

2011-04-01

61

Performance of Clinical Criteria for Screening of Possible Antiretroviral Related Mitochondrial Toxicity in HIV-Infected Children in Accra.  

PubMed

Mitochondrial damage is implicated in highly active antiretroviral therapy (HAART) toxicity. HIV infection also causes mitochondrial toxicity (MT). Differentiating between the two is critical for HIV management. Our objective was to test the utility of the Mitochondrial Disease Criteria (MDC) and the Enquęte Périnatale Française (EPF) to screen for possible HAART related MT in HIV-infected children in Ghana. The EPF and MDC are compilations of clinical symptoms, or criteria, of MT: a (+) score indicates possible MT. We applied these criteria retrospectively to 403 charts of HIV-infected children. Of those studied, 331/403 received HAART. Comparing HAART exposed and HAART naďve children, the difference in EPF score, but not MDC, approached significance (P = 0.1). Young age at HIV diagnosis or at HAART initiation was associated with (+) EPF (P ? 0.01). Adherence to HAART trended toward an association with (+) EPF (P = 0.09). Exposure to nevirapine, abacavir, or didanosine increased risk of (+) EPF (OR = 3.55 (CI = 1.99-6.33), 4.76 (2.39-9.43), 4.93 (1.29-18.87)). Neither EPF nor MDC identified a significant difference between HAART exposed or naďve children regarding possible MT. However, as indicators of HAART exposure are associated with (+) EPF, it may be a candidate for prospective study of possible HAART related MT in resource-poor settings. PMID:23533730

Langs-Barlow, Allison; Renner, Lorna; Katz, Karol; Northrup, Veronika; Paintsil, Elijah

2013-01-01

62

Monocyte/macrophage inflammatory response pathways to combat Francisella infection: possible therapeutic targets?  

PubMed Central

Francisella tularensis can bypass and suppress host immune responses, even to the point of manipulating immune cell phenotypes and intercellular inflammatory networks. Strengthening these responses such that immune cells more readily identify and destroy the bacteria is likely to become a viable (and perhaps necessary) strategy for combating infections with Francisella, especially given the likelihood of antibiotic resistance in the foreseeable future. Monocytes and macrophages offer a niche wherein Francisella can invade and replicate, resulting in substantially higher bacterial load that can overcome the host. As such, understanding their responses to Francisella may uncover potential avenues of therapy that could promote a lowering of bacterial burden and clearance of infection. These response pathways include Toll-like Receptor 2 (TLR2), the caspase-1 inflammasome, Interferons, NADPH oxidase, Phosphatidylinositide 3-kinase (PI3K), and the Ras pathway. In this review we summarize the literature pertaining to the roles of these pathways during Francisella infection, with an emphasis on monocyte/macrophage responses. The therapeutic targeting of one or more such pathways may ultimately become a valuable tool for the treatment of tularemia, and several possibilities are discussed. PMID:24600590

Gillette, Devyn D.; Tridandapani, Susheela; Butchar, Jonathan P.

2014-01-01

63

Targeting the endocannabinoid system with cannabinoid receptor agonists: pharmacological strategies and therapeutic possibilities.  

PubMed

Human tissues express cannabinoid CB(1) and CB(2) receptors that can be activated by endogenously released 'endocannabinoids' or exogenously administered compounds in a manner that reduces the symptoms or opposes the underlying causes of several disorders in need of effective therapy. Three medicines that activate cannabinoid CB(1)/CB(2) receptors are now in the clinic: Cesamet (nabilone), Marinol (dronabinol; ?(9)-tetrahydrocannabinol (?(9)-THC)) and Sativex (?(9)-THC with cannabidiol). These can be prescribed for the amelioration of chemotherapy-induced nausea and vomiting (Cesamet and Marinol), stimulation of appetite (Marinol) and symptomatic relief of cancer pain and/or management of neuropathic pain and spasticity in adults with multiple sclerosis (Sativex). This review mentions several possible additional therapeutic targets for cannabinoid receptor agonists. These include other kinds of pain, epilepsy, anxiety, depression, Parkinson's and Huntington's diseases, amyotrophic lateral sclerosis, stroke, cancer, drug dependence, glaucoma, autoimmune uveitis, osteoporosis, sepsis, and hepatic, renal, intestinal and cardiovascular disorders. It also describes potential strategies for improving the efficacy and/or benefit-to-risk ratio of these agonists in the clinic. These are strategies that involve (i) targeting cannabinoid receptors located outside the blood-brain barrier, (ii) targeting cannabinoid receptors expressed by a particular tissue, (iii) targeting upregulated cannabinoid receptors, (iv) selectively targeting cannabinoid CB(2) receptors, and/or (v) adjunctive 'multi-targeting'. PMID:23108552

Pertwee, Roger G

2012-12-01

64

Regulatory T Cell-Derived Exosomes: Possible Therapeutic and Diagnostic Tools in Transplantation  

PubMed Central

Exosomes are extracellular vesicles released by many cells of the body. These small vesicles play an important part in intercellular communication both in the local environment and systemically, facilitating in the transfer of proteins, cytokines as well as miRNA between cells. The observation that exosomes isolated from immune cells such as dendritic cells (DCs) modulate the immune response has paved the way for these structures to be considered as potential immunotherapeutic reagents. Indeed, clinical trials using DC derived exosomes to facilitate immune responses to specific cancer antigens are now underway. Exosomes can also have a negative effect on the immune response and exosomes isolated from regulatory T cells (Tregs) and other subsets of T cells have been shown to have immune suppressive capacities. Here, we review what is currently known about Treg derived exosomes and their contribution to immune regulation, as well as highlighting their possible therapeutic potential for preventing graft rejection, and use as diagnostic tools to assess transplant outcome. PMID:25414702

Agarwal, Akansha; Fanelli, Giorgia; Letizia, Marilena; Tung, Sim Lai; Boardman, Dominic; Lechler, Robert; Lombardi, Giovanna; Smyth, Lesley A.

2014-01-01

65

DNA vaccination with HIV1 expressing constructs elicits immune responses in humans  

Microsoft Academic Search

Humoral and cellular immune responses have been produced by intramuscular vaccination with DNA plasmids expressing HIV-1 genes, suggesting possible immunotherapeutic and prophylactic value for these constructs. Vaccination with these constructs has decreased HIV-1 viral load in HIV-1-infected chimpanzees. In addition, naive (i.e. non-HIV-1-infected) chimpanzees were protected against a heterologous challenge with HIV-1. Ongoing phase I clinical trials show that therapeutic

Kenneth E. Ugen; Susan B. Nyland; Jean D. Boyer; Cristina Vidal; Liana Lera; Sowsan Rasheid; Michael Chattergoon; Mark L. Bagarazzi; Richard Ciccarelli; Terry Higgins; Yaila Baine; Richard Ginsberg; Rob Roy Macgregor; David B. Weiner

1998-01-01

66

Phase I therapeutic trial of the HIV-1 Tat protein and long term follow-up.  

PubMed

A randomized, double blind, placebo-controlled phase I vaccine trial based on the native Tat protein was conducted in HIV-infected asymptomatic individuals. The vaccine was administered five times subcute with alum or intradermally without adjuvant at 7.5microg, 15microg or 30microg doses, respectively. The Tat vaccine was well tolerated both locally and systemically and induced and/or maintained Tat-specific T helper (Th)-1 T-cell responses and Th-2 responses in all subjects with a wide spectrum of functional anti-Tat antibodies, rarely seen in HIV-infected subjects. The data indicate the achievement of both the primary (safety) and secondary (immunogenicity) endpoints of the study. PMID:19208456

Longo, Olimpia; Tripiciano, Antonella; Fiorelli, Valeria; Bellino, Stefania; Scoglio, Arianna; Collacchi, Barbara; Alvarez, Maria Josč Ruiz; Francavilla, Vittorio; Arancio, Angela; Paniccia, Giovanni; Lazzarin, Adriano; Tambussi, Giuseppe; Din, Chiara Tassan; Visintini, Raffaele; Narciso, Pasquale; Antinori, Andrea; D'Offizi, Gianpiero; Giulianelli, Marina; Carta, Maria; Di Carlo, Aldo; Palamara, Guido; Giuliani, Massimo; Laguardia, Maria Elena; Monini, Paolo; Magnani, Mauro; Ensoli, Fabrizio; Ensoli, Barbara

2009-05-26

67

Exploring the Possibilities and Limitations of Service-Learning: A Critical Analysis of College Student Narratives about HIV/AIDS  

ERIC Educational Resources Information Center

This article reports the results of a study that explored the possibilities and limitations of service-learning by deconstructing the narratives about HIV/AIDS that emerged from five college students who participated in an alternative spring break program. Employing a critical (Rhoads, 1997) and anti-foundational (Butin, 2010) approach to inquiry,…

Jones, Susan Robb; LePeau, Lucy A.; Robbins, Claire K.

2013-01-01

68

Glucagon-like Peptide-1 (GLP-1) Analogs: Recent Advances, New Possibilities, and Therapeutic Implications.  

PubMed

Glucagon-like peptide-1 (GLP-1) is an incretin that plays important physiological roles in glucose homeostasis. Produced from intestine upon food intake, it stimulates insulin secretion and keeps pancreatic ?-cells healthy and proliferating. Because of these beneficial effects, it has attracted a great deal of attention in the past decade, and an entirely new line of diabetic therapeutics has emerged based on the peptide. In addition to the therapeutic applications, GLP-1 analogs have demonstrated a potential in molecular imaging of pancreatic ?-cells; this may be useful in early detection of the disease and evaluation of therapeutic interventions, including islet transplantation. In this Perspective, we focus on GLP-1 analogs for their studies on improvement of biological activities, enhancement of metabolic stability, investigation of receptor interaction, and visualization of the pancreatic islets. PMID:25349901

Manandhar, Bikash; Ahn, Jung-Mo

2015-02-12

69

Modelling the long-term impacts on affected children of adult HIV: benefits, challenges and a possible approach.  

PubMed

We outline the benefits, challenges and possible approaches to developing mathematical models that could be used to estimate the magnitude of negative consequences of adult HIV infection for children. Adult HIV infection can lead to numerous negative consequences for dependent children, including depression, anxiety, withdrawal from school and early sexual debut, among others. For advocacy and planning purposes, it is important to highlight and consider as many of these as possible. A focus solely on orphan numbers, which is the typical summary measure for children affected by HIV and AIDS, can be misleading. The complexity of child development that is characterized by the interaction of a multitude of proximal and distal factors, coupled with a significant lack of data on child development in the context of adult HIV infection make the development of models a challenging task. Although it may not be possible in the first attempt to develop a population-based model capable of examining family dynamics, the negative consequences together with the impact of interventions, steps in that direction can be taken. We propose approaches and assumptions that we believe will allow the development of a useful first set of models. We conclude with a brief discussion of the type of data that, if collected, would facilitate refinement and development of these models. PMID:24991900

Desmond, Christopher; Bruce, Faikah; Tomlinson, M; Marlow, Marguerite B; Aber, J Lawrence; Ouifki, Rachid; Welte, Alex

2014-07-01

70

A Future of Possibilities: Educating Children Living in HIV Impacted Households  

ERIC Educational Resources Information Center

Close to one and a half million Kenyans reportedly live with HIV/AIDS. Using qualitative in-depth interviews this study explores the ways in which parents living with HIV/AIDS navigate their social and economic environment to provide educational opportunities for their children. Barriers identified include the economic costs of a free primary…

Kagotho, Njeri

2012-01-01

71

Interactions between prostaglandins, leukotrienes and HIV-1: Possible implications for the central nervous system  

PubMed Central

In HIV-1-infected individuals, there is often discordance between viremia in peripheral blood and viral load found in the central nervous system (CNS). Although the viral burden is often lower in the CNS compartment than in the plasma, neuroinflammation is present in most infected individuals, albeit attenuated by the current combined antiretroviral therapy. The HIV-1-associated neurological complications are thought to result not only from direct viral replication, but also from the subsequent neuroinflammatory processes. The eicosanoids - prostanoids and leukotrienes - are known as potent inflammatory lipid mediators. They are often present in neuroinflammatory diseases, notably HIV-1 infection. Their exact modulatory role in HIV-1 infection is, however, still poorly understood, especially in the CNS compartment. Nonetheless, a handful of studies have provided evidence as to how these lipid mediators can modulate HIV-1 infection. This review summarizes findings indicating how eicosanoids may influence the progression of neuroAIDS. PMID:22236409

2012-01-01

72

JAM-A and ALCAM are therapeutic targets to inhibit diapedesis across the BBB of CD14+CD16+ monocytes in HIV-infected individuals.  

PubMed

Monocyte transmigration across the BBB is a critical step in the development of cognitive deficits termed HAND that affect 40-70% of HIV-infected individuals, even with successful antiretroviral therapy. The monocyte subsets that enter the CNS during HIV infection are not fully characterized. We examined PBMC from HIV-positive individuals from 2 distinct cohorts and enumerated monocyte populations, characterized their transmigration properties across an in vitro human BBB model, and identified surface proteins critical for the entry of these cells into the CNS. We demonstrated that the frequency of peripheral blood CD14(+)CD16(+) and CD14(low)CD16(+) monocytes was increased in HIV-seropositive compared with -seronegative individuals, despite virologic control. We showed that CD14(+)CD16(+) monocytes selectively transmigrated across our BBB model as a result of their increased JAM-A and ALCAM expression. Antibody blocking of these proteins inhibited diapedesis of CD14(+)CD16(+) monocytes but not of T cells from the same HIV-infected people across the BBB. Our data indicate that JAM-A and ALCAM are therapeutic targets to decrease the entry of CD14(+)CD16(+) monocytes into the CNS of HIV-seropositive individuals, contributing to the eradication of neuroinflammation, HAND, and CNS viral reservoirs. PMID:25420915

Williams, Dionna W; Anastos, Kathryn; Morgello, Susan; Berman, Joan W

2015-02-01

73

Possible therapeutic effect of a Traditional Chinese Medicine, Sinisan, on chronic restraint stress related disorders  

Microsoft Academic Search

According to Traditional Chinese Medicine (TCM), the liver is the origin or most associated with stress related disorders such as depression. Sinisan, a TCM prescription, has been used as a hepatic protectant. We examined whether Sinisan exerts therapeutic effects in an experimental animal model: the chronic restraint stress (CRS) model. Sinisan was administered in the animal's drinking water at a

Yu-Tong Wang; Qing-Rong Tan; Li-Li Sun; Jun Cao; Ke-Feng Dou; Bing Xia; Wen Wang

2009-01-01

74

Autologous aldrithiol-2-inactivated HIV-1 combined with polyinosinic-polycytidylic acid-poly-L-lysine carboxymethylcellulose as a vaccine platform for therapeutic dendritic cell immunotherapy.  

PubMed

Therapeutic interventions for HIV-1 that successfully augment adaptive immunity to promote killing of infected cells may be a requisite component of strategies to reduce latent cellular reservoirs. Adoptive immunotherapies utilizing autologous monocyte-derived dendritic cells (DCs) that have been activated and antigen loaded ex vivo may serve to circumvent defects in DC function that are present during HIV infection in order to enhance adaptive immune responses. Here we detail the clinical preparation of DCs loaded with autologous aldrithiol-2 (AT-2)-inactivated HIV that have been potently activated with the viral mimic, Polyinosinic-polycytidylic acid-poly-l-lysine carboxymethylcellulose (Poly-ICLC). HIV is first propagated from CD4+ T cells from HIV-infected donors and then rendered non-replicative by chemical inactivation with aldrithiol-2 (AT-2), purified, and quantified. Viral inactivation is confirmed through measurement of Tat-regulated ?-galactosidase reporter gene expression following infection of TZM-bl cells. In-process testing for sterility, mycoplasma, LPS, adventitious agents, and removal of AT-2 is performed on viral preparations. Autologous DCs are generated and pulsed with autologous AT-2-inactivated virus and simultaneously stimulated with Poly-ICLC to constitute the final DC vaccine product. Phenotypic identity, maturation, and induction of HIV-specific adaptive immune responses are confirmed via flow cytometric analysis of DCs and cocultured autologous CD4+ and CD8+ T cells. Lot release criteria for the DC vaccine have been defined in accordance with Good Manufacturing Practice (GMP) guidelines. The demonstrated feasibility of this approach has resulted in approval by the FDA for investigational use in antiretroviral (ART) suppressed individuals. We discuss how this optimized DC formulation may enhance the quality of anti-HIV adaptive responses beyond what has been previously observed during DC immunotherapy trials for HIV infection. PMID:25444812

Miller, Elizabeth; Spadaccia, Meredith; Sabado, Rachel; Chertova, Elena; Bess, Julian; Trubey, Charles Mac; Holman, Rose Marie; Salazar, Andres; Lifson, Jeffrey; Bhardwaj, Nina

2015-01-01

75

[Chronic disorders after interventions in the anorectal area--therapeutic possibilities].  

PubMed

Long lasting alterations of anal function and persistent pain in a few patients after ano-rectal operations are a great therapeutic problem. Sometimes more than 6 months after LAR there are complaints about incontinence, disturbance connected to a spastic evacuation--whereas pain is more often connected with the situation after Stapler hemorrhiodectomy or other anal interventions. The therapeutic management has to consider all etiological factors and consists mainly of conservative therapy, including regulation of stool volume, slow-down of colon transit, strengthening of anal and pelvic floor muscles, regulation of co-ordination and ability of relaxation and straining, therapy of pain and--last not least--psychological support. PMID:12704876

Geile, D; Haseitl, M; Osterholzer, G

2002-01-01

76

[Transgenic cell cultures that synthesize neurotrophic factors and the possibility of therapeutic use of its cells].  

PubMed

Under the leadership of Corresponding Member of the Russian Academy of Sciences L.I. Korochkin, the Laboratory of Neurogenetics and Developmental Genetics (Institute of Gene Biology, Russian Academy of Sciences) for many years has been conducting studies of nervous system development, neural cell differentiation, and application of gene and cell technology to cure neurodegenerative diseases. The results of the study initiated by L.I. Korochkin and continued by his scientific successors support the direction of allocation of transgenic neurotrofic factors and heat-shock proteins as neuroprotectors for cell therapy. Potential for usage of promoter of HSP70 heat-shock gene of Drosophila to create transgenic constructs for therapy has been shown. Further improvement of technology of nonvirus transfer for therapeutic genes, as well as production of multicomponent genetic constructs coding several therapeutic factors with synergy effect, would stimulate creation of efficient cell medicals to cure neurodegenerative diseases. PMID:22567930

Pavlova, G V; Kana?kina, N N; Panteleev, D Iu; Okhotin, V E; Revishchin, A V

2012-01-01

77

Degrasyn-like Symmetrical Compounds: Possible Therapeutic Agents for Multiple Myeloma (MM-I)  

PubMed Central

A series of degrasyn-like symmetrical compounds have been designed, synthesized, and screened against B cell malignancy (multiple myeloma, mantle cell lymphoma) cell lines. The lead compounds T5165804 and CP2005 showed higher nanomolar potency against these tumor cells in comparison to degrasyn and inhibited Usp9x activity in vitro and in intact cells. These observations suggest that this new class of compounds holds promise as cancer therapeutic agents PMID:24457091

Peng, Zhenghong; Maxwell, David; Sun, Duoli; Bhanu Prasad, Basvoju A.; Schuber, Paul T.; Pal, Ashutosh; Ying, Yunming; Han, Dongmei; Gao, Liwei; Wang, Shimei; Levitzki, Alexander; Kapuria, Vaibhav; Talpaz, Moshe; Young, Matthew; Showalter, Hollis D.; Donato, Nicholas J.; Bornmann, William. G.

2014-01-01

78

Targeting specific HATs for neurodegenerative disease treatment: translating basic biology to therapeutic possibilities  

PubMed Central

Dynamic epigenetic regulation of neurons is emerging as a fundamental mechanism by which neurons adapt their transcriptional responses to specific developmental and environmental cues. While defects within the neural epigenome have traditionally been studied in the context of early developmental and heritable cognitive disorders, recent studies point to aberrant histone acetylation status as a key mechanism underlying acquired inappropriate alterations of genome structure and function in post-mitotic neurons during the aging process. Indeed, it is becoming increasingly evident that chromatin acetylation status can be impaired during the lifetime of neurons through mechanisms related to loss of function of histone acetyltransferase (HAT) activity. Several HATs have been shown to participate in vital neuronal functions such as regulation of neuronal plasticity and memory formation. As such, dysregulation of such HATs has been implicated in the pathogenesis associated with age-associated neurodegenerative diseases and cognitive decline. In order to counteract the loss of HAT function in neurodegenerative diseases, the current therapeutic strategies involve the use of small molecules called histone deacetylase (HDAC) inhibitors that antagonize HDAC activity and thus enhance acetylation levels. Although this strategy has displayed promising therapeutic effects, currently used HDAC inhibitors lack target specificity, raising concerns about their applicability. With rapidly evolving literature on HATs and their respective functions in mediating neuronal survival and higher order brain function such as learning and memory, modulating the function of specific HATs holds new promises as a therapeutic tool in neurodegenerative diseases. In this review, we focus on the recent progress in research regarding epigenetic histone acetylation mechanisms underlying neuronal activity and cognitive function. We discuss the current understanding of specific HDACs and HATs in neurodegenerative diseases and the future promising prospects of using specific HAT based therapeutic approaches. PMID:23543406

Pirooznia, Sheila K.; Elefant, Felice

2013-01-01

79

Targeting specific HATs for neurodegenerative disease treatment: translating basic biology to therapeutic possibilities.  

PubMed

Dynamic epigenetic regulation of neurons is emerging as a fundamental mechanism by which neurons adapt their transcriptional responses to specific developmental and environmental cues. While defects within the neural epigenome have traditionally been studied in the context of early developmental and heritable cognitive disorders, recent studies point to aberrant histone acetylation status as a key mechanism underlying acquired inappropriate alterations of genome structure and function in post-mitotic neurons during the aging process. Indeed, it is becoming increasingly evident that chromatin acetylation status can be impaired during the lifetime of neurons through mechanisms related to loss of function of histone acetyltransferase (HAT) activity. Several HATs have been shown to participate in vital neuronal functions such as regulation of neuronal plasticity and memory formation. As such, dysregulation of such HATs has been implicated in the pathogenesis associated with age-associated neurodegenerative diseases and cognitive decline. In order to counteract the loss of HAT function in neurodegenerative diseases, the current therapeutic strategies involve the use of small molecules called histone deacetylase (HDAC) inhibitors that antagonize HDAC activity and thus enhance acetylation levels. Although this strategy has displayed promising therapeutic effects, currently used HDAC inhibitors lack target specificity, raising concerns about their applicability. With rapidly evolving literature on HATs and their respective functions in mediating neuronal survival and higher order brain function such as learning and memory, modulating the function of specific HATs holds new promises as a therapeutic tool in neurodegenerative diseases. In this review, we focus on the recent progress in research regarding epigenetic histone acetylation mechanisms underlying neuronal activity and cognitive function. We discuss the current understanding of specific HDACs and HATs in neurodegenerative diseases and the future promising prospects of using specific HAT based therapeutic approaches. PMID:23543406

Pirooznia, Sheila K; Elefant, Felice

2013-01-01

80

Breast cancer phenotypes regulated by tissue factor-factor VII pathway: Possible therapeutic targets  

PubMed Central

Breast cancer is a leading cause of cancer death in women, worldwide. Fortunately, breast cancer is relatively chemosensitive, with recent advances leading to the development of effective therapeutic strategies, significantly increasing disease cure rate. However, disease recurrence and treatment of cases lacking therapeutic molecular targets, such as epidermal growth factor receptor 2 and hormone receptors, referred to as triple-negative breast cancers, still pose major hurdles in the treatment of breast cancer. Thus, novel therapeutic approaches to treat aggressive breast cancers are essential. Blood coagulation factor VII (fVII) is produced in the liver and secreted into the blood stream. Tissue factor (TF), the cellular receptor for fVII, is an integral membrane protein that plays key roles in the extrinsic coagulation cascade. TF is overexpressed in breast cancer tissues. The TF-fVII complex may be formed in the absence of injury, because fVII potentially exists in the tissue fluid within cancer tissues. The active form of this complex (TF-fVIIa) may stimulate the expression of numerous malignant phenotypes in breast cancer cells. Thus, the TF-fVII pathway is a potentially attractive target for breast cancer treatment. To date, a number of studies investigating the mechanisms by which TF-fVII signaling contributes to breast cancer progression, have been conducted. In this review, we summarize the mechanisms controlling TF and fVII synthesis and regulation in breast cancer cells. Our current understanding of the TF-fVII pathway as a mediator of breast cancer progression will be also described. Finally, we will discuss how this knowledge can be applied to the design of future therapeutic strategies. PMID:25493229

Koizume, Shiro; Miyagi, Yohei

2014-01-01

81

HIV  

PubMed Central

Getting to zero: zero new HIV infections, zero deaths from AIDS-related illness, zero discrimination is the theme of World AIDS Day 2012. Given the spread of the epidemic today, getting to zero may sound difficult, but significant progress is underway. The total annual loss for the entire country due to HIV is 7% of GDP, which exceeds India’s annual health expenditure in 2004. The additional loss due to loss of labor income and increased medical expenditure as measured by the external transfers, account for 5% of the country’s health expenditure and 0.23% of GDP. Given that the HIV incidence rate is only 0.27% in India, these losses are quite staggering. Despite the remarkable achievements in development of anti-retroviral therapies against HIV and the recent advances in new prevention technologies, the rate of new HIV infections continue to outpace efforts on HIV prevention and control. Thus, the development of a safe and effective vaccine for prevention and control of AIDS remains a global public health priority and the greatest opportunity to eventually end the AIDS pandemic. PMID:24056755

Chawla, Sumit; Sahoo, Soumya Swaroop; Jain, Rambilas; Khanna, Pardeep; Mehta, Bharti; Singh, Inderjeet

2014-01-01

82

Vascular endothelial growth factor: therapeutic possibilities and challenges for the treatment of ischemia.  

PubMed

Vascular endothelial growth factor (VEGF) is a notable chemokine that plays critical roles in angiogenesis and vasculogenesis. The contemporary body of literature contains a substantial amount of information regarding its chemical properties as well as its fundamental role in vascular development. Studies strongly indicate its potential use as a therapeutic agent, especially in the vascular restoration of injured and ischemic tissues. VEGF therapy could be most beneficial for diseases whose pathologies revolve around tissue inflammation and necrosis, such as myocardial infarction and stroke, as well as ischemic bowel diseases such as acute mesenteric ischemia and necrotizing enterocolitis. However, a delicate balance exists between the therapeutic benefits of VEGF and the hazards of tumor growth and neo-angiogenesis. Effective future research surrounding VEGF may allow for the development of effective therapies for ischemia which simultaneously limit its more deleterious side effects. This review will: (1) summarize the current understanding of the molecular aspects and function of VEGF, (2) review potential benefits of its use in medical therapy, (3) denote its role in tumorigenesis and inflammation when overexpressed, and (4) elucidate the qualities which make it a viable compound of study for diagnostic and therapeutic applications. PMID:25240960

Crafts, Trevor D; Jensen, Amanda R; Blocher-Smith, Ethan C; Markel, Troy A

2015-02-01

83

The latest progress in research on triple negative breast cancer (TNBC): risk factors, possible therapeutic targets and prognostic markers  

PubMed Central

Triple negative breast cancer (TNBC) is one type of breast cancer (BC), which is defined as negative for estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (Her2). Its origins and development seem to be elusive. And for now, drugs like tamoxifen or trastuzumab which specifically apply to ER, PR or Her2 positive BC seem unforeseeable in TNBC clinical treatment. Due to its extreme malignancy, high recurrence rate and poor prognosis, a lot of work on the research of TNBC is needed. This review aims to summarize the latest findings in TNBC in risk factors, possible therapeutic targets and possible prognostic makers. PMID:25276378

Jiao, Qingli; Shao, Guoli; Peng, Haoyu; Wang, Mengchuan; Ji, Shufeng; Liu, Peng; Zhang, Jian

2014-01-01

84

Acceptability and effectiveness of chickpea sesame-based ready-to-use therapeutic food in malnourished HIV-positive adults  

PubMed Central

Objective: A prospective descriptive study to assess acceptability and effectiveness of a locally made ready-to-use therapeutic food (RUTF) in HIV-infected chronically sick adults (CSA) with mid-upper-arm circumference (MUAC) <210 mm or pitting edema. Methods: Sixty-three wasted AIDS adults were prescribed 500 g representing ~2600 kcal/day of locally made RUTF for three months and routine cotrimoxazole. Weight, height, MUAC, Karnofsky score and morbidity were measured at admission and at monthly intervals. The amount of RUTF intake and acceptability were assessed monthly. Results: Ninety-five percent (60/63) of the CSA that were invited to join the study agreed to participate. Mean daily intake in these 60 patients was 300 g/person/day (~1590 Kcal and 40 g of protein). Overall, 73.3% (44/60) gained weight, BMI, and MUAC. The median weight, MUAC and BMI gains after three months were 3.0 kg, 25.4 mm, and 1.1 kg/m2, respectively. The intervention improved the physical activity performance of participants and 78.3% (47/60) regained sufficient strength to walk to the nearest health facility. Mortality at three months was 18.3% (11/60). Conclusion: Locally made RUTF was acceptable to patients and was associated with a rapid weight gain and physical activity performance. The intervention is likely to be more cost effective than nutritional support using usual food-aid commodities. PMID:19936147

Bahwere, Paluku; Sadler, Kate; Collins, Steve

2009-01-01

85

Current concepts of platelet activation: possibilities for therapeutic modulation of heterotypic vs. homotypic aggregation  

PubMed Central

Thrombogenic and inflammatory activity are two distinct aspects of platelet biology, which are sustained by the ability of activated platelets to interact with each other (homotypic aggregation) and to adhere to circulating leucocytes (heterotypic aggregation). These two events are regulated by distinct biomolecular mechanisms that are selectively activated in different pathophysiological settings. They can occur simultaneously, for example, as part of a pro-thrombotic/pro-inflammatory response induced by vascular damage, or independently, as in certain clinical conditions in which abnormal heterotypic aggregation has been observed in the absence of intravascular thrombosis. Current antiplatelet drugs have been developed to target specific molecular signalling pathways mainly implicated in thrombus formation, and their ever increasing clinical use has resulted in clear benefits in the treatment and prevention of arterial thrombotic events. However, the efficacy of currently available antiplatelet drugs remains suboptimal, most likely because their therapeutic action is limited to only few of the signalling pathways involved in platelet homotypic aggregation. In this context, modulation of heterotypic aggregation, which is believed to contribute importantly to acute thrombotic events, as well to the pathophysiology of atherosclerosis itself, may offer benefits over and above the classical antiplatelet approach. This review will focus on the distinct biomolecular pathways that, following platelet activation, underlie homotypic and heterotypic aggregation, aiming potentially to identify novel therapeutic targets. PMID:21223359

Passacquale, Gabriella; Ferro, Albert

2011-01-01

86

Methylation profile landscape in mesothelioma: possible implications in early detection, disease progression, and therapeutic options.  

PubMed

Malignant Pleural Mesothelioma (MPM) is an aggressive malignancy of the pleura associated with asbestos exposure. Incidence of MPM is expected to increase over the course of next decade in both Europe and the developing countries. Although significant progress has been made in terms of etiology and pathogenesis of this disease, currently available therapeutic options have not significantly improved the survival outcome of patients on standard chemotherapeutic regimens. Integrity of the cellular DNA is often altered in many cancers. Understanding of the molecular mechanisms that regulate cellular DNA alterations to facilitate cancer initiation and development has potential to allow better design of cancer cell inhibitory strategies. In this context, there is a need to explore the gamut of "omics" strategies to provide a comprehensive epigenetics profile for MPM. This chapter discusses the functional genomics and epigenetic patterns observed by various investigators studying MPM patient populations on global fronts, and attempts to present a holistic approach in combating this insidious disease. Here we provide investigators in this field with novel insights and methodologies used in other types of cancers that might have profound impact in the early detection, prognosis and potential therapeutic strategies for MPM. PMID:25421663

Zhang, Xinbo; Tang, Naimei; Rishi, Arun K; Pass, Harvey I; Wali, Anil

2015-01-01

87

Preventive HIV Vaccines What is a vaccine?  

E-print Network

Preventive HIV Vaccines What is a vaccine? A vaccine is a medical product designed to stimulate infection or make you sick. What is the difference between a preventive HIV vaccine and a therapeutic HIV vaccine? Therapeutic HIV vaccines are designed to control HIV infection in people who are already HIV

Levin, Judith G.

88

Melatonin and Its Agonist Ramelteon in Alzheimer's Disease: Possible Therapeutic Value  

PubMed Central

Alzheimer's disease (AD) is an age-associated neurodegenerative disease characterized by the progressive loss of cognitive function, loss of memory and insomnia, and abnormal behavioral signs and symptoms. Among the various theories that have been put forth to explain the pathophysiology of AD, the oxidative stress induced by amyloid ?-protein (A?) deposition has received great attention. Studies undertaken on postmortem brain samples of AD patients have consistently shown extensive lipid, protein, and DNA oxidation. Presence of abnormal tau protein, mitochondrial dysfunction, and protein hyperphosphorylation all have been demonstrated in neural tissues of AD patients. Moreover, AD patients exhibit severe sleep/wake disturbances and insomnia and these are associated with more rapid cognitive decline and memory impairment. On this basis, the successful management of AD patients requires an ideal drug that besides antagonizing A?-induced neurotoxicity could also correct the disturbed sleep-wake rhythm and improve sleep quality. Melatonin is an effective chronobiotic agent and has significant neuroprotective properties preventing A?-induced neurotoxic effects in a number of animal experimental models. Since melatonin levels in AD patients are greatly reduced, melatonin replacement has the potential value to be used as a therapeutic agent for treating AD, particularly at the early phases of the disease and especially in those in whom the relevant melatonin receptors are intact. As sleep deprivation has been shown to produce oxidative damage, impaired mitochondrial function, neurodegenerative inflammation, and altered proteosomal processing with abnormal activation of enzymes, treatment of sleep disturbances may be a priority for arresting the progression of AD. In this context the newly introduced melatonin agonist ramelteon can be of much therapeutic value because of its highly selective action on melatonin MT1/MT2 receptors in promoting sleep. PMID:21197086

Srinivasan, Venkatramanujam; Kaur, Charanjit; Pandi-Perumal, Seithikurippu; Brown, Gregory M.; Cardinali, Daniel P.

2011-01-01

89

Melatonin and its agonist ramelteon in Alzheimer's disease: possible therapeutic value.  

PubMed

Alzheimer's disease (AD) is an age-associated neurodegenerative disease characterized by the progressive loss of cognitive function, loss of memory and insomnia, and abnormal behavioral signs and symptoms. Among the various theories that have been put forth to explain the pathophysiology of AD, the oxidative stress induced by amyloid ?-protein (A?) deposition has received great attention. Studies undertaken on postmortem brain samples of AD patients have consistently shown extensive lipid, protein, and DNA oxidation. Presence of abnormal tau protein, mitochondrial dysfunction, and protein hyperphosphorylation all have been demonstrated in neural tissues of AD patients. Moreover, AD patients exhibit severe sleep/wake disturbances and insomnia and these are associated with more rapid cognitive decline and memory impairment. On this basis, the successful management of AD patients requires an ideal drug that besides antagonizing A?-induced neurotoxicity could also correct the disturbed sleep-wake rhythm and improve sleep quality. Melatonin is an effective chronobiotic agent and has significant neuroprotective properties preventing A?-induced neurotoxic effects in a number of animal experimental models. Since melatonin levels in AD patients are greatly reduced, melatonin replacement has the potential value to be used as a therapeutic agent for treating AD, particularly at the early phases of the disease and especially in those in whom the relevant melatonin receptors are intact. As sleep deprivation has been shown to produce oxidative damage, impaired mitochondrial function, neurodegenerative inflammation, and altered proteosomal processing with abnormal activation of enzymes, treatment of sleep disturbances may be a priority for arresting the progression of AD. In this context the newly introduced melatonin agonist ramelteon can be of much therapeutic value because of its highly selective action on melatonin MT(1)/MT(2) receptors in promoting sleep. PMID:21197086

Srinivasan, Venkatramanujam; Kaur, Charanjit; Pandi-Perumal, Seithikurippu; Brown, Gregory M; Cardinali, Daniel P

2010-01-01

90

Disrupted chronobiology of sleep and cytoprotection in obesity: possible therapeutic value of melatonin.  

PubMed

From a physiological perspective the sleep-wake cycle can be envisioned as a sequence of three physiological states (wakefulness, non-rapid eye movement, NREM, sleep and REM sleep) which are defined by a particular neuroendocrine-immune profile regulating the metabolic balance, body weight and inflammatory responses. Sleep deprivation and circadian disruption in contemporary "24/7 Society" lead to the predominance of pro-orexic and proinflammatory mechanisms that contribute to a pandemic metabolic syndrome (MS) including obesity, diabetes and atherosclerotic disease. Thus, a successful management of MS may require a drug that besides antagonizing the trigger factors of MS could also correct a disturbed sleep-wake rhythm. This review deals with the analysis of the therapeutic validity of melatonin in MS. Melatonin is an effective chronobiotic agent changing the phase and amplitude of the sleep/wake rhythm and having cytoprotective and immunomodulatory properties useful to prevent a number of MS sequels. Several studies support that melatonin can prevent hyperadiposity in animal models of obesity. Melatonin at a low dose (2-5 mg/day) has been used for improving sleep in patients with insomnia and circadian rhythm sleep disorders. More recently, attention has been focused on the development of potent melatonin analogs with prolonged effects (ramelteon, agomelatine, tasimelteon, TK 301). In clinical trials these analogs were employed in doses considerably higher than those usually employed for melatonin. In view that the relative potencies of the analogs are higher than that of the natural compound, clinical trials employing melatonin doses in the range of 50-100 mg/day are needed to assess its therapeutic value in MS. PMID:22167135

Cardinali, Daniel P; Pagano, Eleonora S; Scacchi Bernasconi, Pablo A; Reynoso, Roxana; Scacchi, Pablo

2011-01-01

91

Nitric oxide synthase inhibition and oxidative stress in cardiovascular diseases: possible therapeutic targets?  

PubMed

Nitric oxide (NO) is synthetized enzymatically from l-arginine (l-Arg) by three NO synthase isoforms, iNOS, eNOS and nNOS. The synthesis of NO is selectively inhibited by guanidino-substituted analogs of l-Arg or methylarginines such as asymmetric dimethylarginine (ADMA), which results from protein degradation in cells. Many disease states, including cardiovascular diseases and diabetes, are associated with increased plasma levels of ADMA. The N-terminal catalytic domain of these NOS isoforms binds the heme prosthetic group as well as the redox cofactor, tetrahydrobiopterin (BH(4)) associated with a regulatory protein, calmodulin (CaM). The enzymatic activity of NOS depends on substrate and cofactor availability. The importance of BH(4) as a critical regulator of eNOS function suggests that BH(4) may be a rational therapeutic target in vascular disease states. BH(4) oxidation appears to be a major contributor to vascular dysfunction associated with hypertension, ischemia/reperfusion injury, diabetes and other cardiovascular diseases as it leads to the increased formation of oxygen-derived radicals due to NOS uncoupling rather than NO. Accordingly, abnormalities in vascular NO production and transport result in endothelial dysfunction leading to various cardiovascular disorders. However, some disorders including a wide range of functions in the neuronal, immune and cardiovascular system were associated with the over-production of NO. Inhibition of the enzyme should be a useful approach to treat these pathologies. Therefore, it appears that both a lack and excess of NO production in diseases can have various important pathological implications. In this context, NOS modulators (exogenous and endogenous) and their therapeutic effects are discussed. PMID:23859953

Rochette, Luc; Lorin, Julie; Zeller, Marianne; Guilland, Jean-Claude; Lorgis, Luc; Cottin, Yves; Vergely, Catherine

2013-12-01

92

IL-23 in Infections, Inflammation, Autoimmunity and Cancer: Possible Role in HIV-1 and AIDS  

PubMed Central

The growing family of interleukin (IL)-12-like cytokines produced by activated macrophages and dendritic cells became the important players in the control of infections, development of inflammation, autoimmunity and cancer. However, the role of one of them—heterodimer IL-23, which consists of IL12p40 and the unique p19 subunit in HIV-1 infection pathogenesis and progression to AIDS, represent special interest. We overviewed findings of IL-23 involvement in control of peripheral bacterial pathogens and opportunistic infection, central nervous system (CNS) viral infections and autoimmune disorders, and tumorogenesis, which potentially could be applicable to HIV-1 and AIDS. PMID:21947740

Yannam, Govardhana Rao; Gutti, Tanuja

2011-01-01

93

Association of Oxidative Stress to the Genesis of Anxiety: Implications for Possible Therapeutic Interventions  

PubMed Central

Oxidative stress caused by reactive species, including reactive oxygen species, reactive nitrogen species, and unbound, adventitious metal ions (e.g., iron [Fe] and copper [Cu]), is an underlying cause of various neurodegenerative diseases. These reactive species are an inevitable by-product of cellular respiration or other metabolic processes that may cause the oxidation of lipids, nucleic acids, and proteins. Oxidative stress has recently been implicated in depression and anxiety-related disorders. Furthermore, the manifestation of anxiety in numerous psychiatric disorders, such as generalized anxiety disorder, depressive disorder, panic disorder, phobia, obsessive-compulsive disorder, and posttraumatic stress disorder, highlights the importance of studying the underlying biology of these disorders to gain a better understanding of the disease and to identify common biomarkers for these disorders. Most recently, the expression of glutathione reductase 1 and glyoxalase 1, which are genes involved in antioxidative metabolism, were reported to be correlated with anxiety-related phenotypes. This review focuses on direct and indirect evidence of the potential involvement of oxidative stress in the genesis of anxiety and discusses different opinions that exist in this field. Antioxidant therapeutic strategies are also discussed, highlighting the importance of oxidative stress in the etiology, incidence, progression, and prevention of psychiatric disorders. PMID:24669207

Hassan, Waseem; Silva, Carlos Eduardo Barroso; Mohammadzai, Imdad Ullah; da Rocha, Joao Batista Teixeira; Landeira-Fernandez, J.

2014-01-01

94

Therapeutic Possibilities of Ceftazidime Nanoparticles in Devastating Pseudomonas Ophthalmic Infections; Keratitis and Endophthalmitis  

PubMed Central

As the number of contact?lens wearers rises worldwide, Pseudomonas aeruginosa (PA) keratitis is attracting more attention as a major public health issue. Corneal lesions of PA, being the most intimidating complication of contact?lens wearer, can progress rapidly in spite of local antibiotic treatment, and may result in perforation and the permanent loss of vision. One of the explanations proposed for the evasion of the pathogen from immune responses of the host as well as antibacterial treatment is the fact that invasive clinical isolates of PA have the unusual ability to invade and replicate within surface corneal epithelial cells. In this manner, PA is left with an intracellular sanctuary. Endophthalmitis, albeit rare, is another ophthalmic infection faced by the challenge of drug delivery that can be potentially catastrophic. The present hypothesis is that nanoparticles can carry anti?pseudomonas antibiotics (e.g. ceftazidime) through the membranes, into the “hidden zone” of the pathogen, hence being an effective and potent therapeutic approach against pseudomonas keratitis and endophthalmitis. PMID:24600610

Mohammadpour, Mehrdad; Jabbarvand, Mahmood; Karimi, Nasser

2012-01-01

95

[Difficulties of psychosomatic clients in assessing personal emotions and motives: possible consequences for therapeutic treatment].  

PubMed

In this work the degree of explication accomplished in a focusing process by 33 persons suffering psychosomatic disorder was compared with that attained by 33 persons in a control group. On the basis of a general psychological conception of focusing process a therapeutical action model was developed which offers concrete action directives to the therapist to deal with different behaviour patterns of clients. It was argumented that persons who exhibit action-directing motives of which they are not aware or which they do not understand due to their great distance to internal experiencing, run a higher risk to experience massive stresses in their struggle with the environment frequently with psychophysiological dysfunctions. In the experimental part of this work it was shown that, as compared with the probands of the comparison group, this therapy method was less beneficial for persons with psychosomatic ailments both with respect to self-experiencing and assessment by others, in that they less distinctly approached the focusing goal and optimum process characteristics. PMID:1871251

Sachse, R; Atrops, A

1991-05-01

96

Therapeutic possibilities of ceftazidime nanoparticles in devastating pseudomonas ophthalmic infections; keratitis and endophthalmitis.  

PubMed

As the number of contact-lens wearers rises worldwide, Pseudomonas aeruginosa (PA) keratitis is attracting more attention as a major public health issue. Corneal lesions of PA, being the most intimidating complication of contact-lens wearer, can progress rapidly in spite of local antibiotic treatment, and may result in perforation and the permanent loss of vision. One of the explanations proposed for the evasion of the pathogen from immune responses of the host as well as antibacterial treatment is the fact that invasive clinical isolates of PA have the unusual ability to invade and replicate within surface corneal epithelial cells. In this manner, PA is left with an intracellular sanctuary. Endophthalmitis, albeit rare, is another ophthalmic infection faced by the challenge of drug delivery that can be potentially catastrophic. The present hypothesis is that nanoparticles can carry anti-pseudomonas antibiotics (e.g. ceftazidime) through the membranes, into the "hidden zone" of the pathogen, hence being an effective and potent therapeutic approach against pseudomonas keratitis and endophthalmitis. PMID:24600610

Mohammadpour, Mehrdad; Jabbarvand, Mahmood; Karimi, Nasser

2012-01-01

97

Sonic Hedgehog Signaling Drives Proliferation of Synoviocytes in Rheumatoid Arthritis: A Possible Novel Therapeutic Target  

PubMed Central

Sonic hedgehog (Shh) signaling controls many aspects of human development, regulates cell growth and differentiation in adult tissues, and is activated in a number of malignancies. Rheumatoid arthritis (RA) is characterized by chronic synovitis and pannus formation associated with activation of fibroblast-like synoviocytes (FLS). We investigated whether Shh signaling plays a role in the proliferation of FLS in RA. Expression of Shh signaling related components (Shh, Ptch1, Smo, and Gli1) in RA synovial tissues was examined by immunohistochemistry (IHC) and in FLS by IHC, immunofluorescence (IF), quantitative RT-PCR, and western blotting. Expression of Shh, Smo, and Gli1 in RA synovial tissue was higher than that in control tissue (P < 0.05). Cyclopamine (a specific inhibitor of Shh signaling) decreased mRNA expression of Shh, Ptch1, Smo, and Gli1 in cultured RA FLS, Shh, and Smo protein expression, and significantly decreased FLS proliferation. Flow cytometry analysis suggested that cyclopamine treatment resulted in cell cycle arrest of FLS in G1 phase. Our data show that Shh signaling is activated in synovium of RA patients in vivo and in cultured FLS form RA patients in vitro, suggesting a role in the proliferation of FLS in RA. It may therefore be a novel therapeutic target in RA. PMID:24741597

Wang, Mingxia; Zhu, Shangling; Peng, Weixiang; Li, Qiuxia; Li, Zhaoxia; Luo, Minqi; Feng, Xiaoxue; Lin, Zhuofeng; Huang, Jianlin

2014-01-01

98

Immune reconstitution inflammatory syndrome in association with HIV\\/AIDS and tuberculosis: Views over hidden possibilities  

Microsoft Academic Search

Gut immune components are severely compromised among persons with AIDS, which allows increased translocation of bacterial lipopolysaccharides (LPS) into the systemic circulation. These microbial LPS are reportedly increased in chronically HIV-infected individuals and findings have correlated convincingly with measures of immune activation. Immune reconstitution inflammatory syndrome (IRIS) is an adverse consequence of the restoration of pathogen-specific immune responses in a

Esaki Muthu Shankar; Ramachandran Vignesh; Kailapuri G Murugavel; Pachamuthu Balakrishnan; Ramalingam Sekar; Charmaine AC Lloyd; Suniti Solomon; Nagalingeswaran Kumarasamy

2007-01-01

99

[Extending therapeutic possibilities in relapsing-remitting multiple sclerosis: dimethyl fumarate].  

PubMed

Dimethyl fumarate (DMF) is a novel oral therapy that has recently been approved for the treatment of relapsing-remitting multiple sclerosis (RRMS). Dimethyl fumarate shows anti-inflammatory and cytoprotective properties that are thought to be mediated primarily via activation of the nuclear factor (erythroid-derived 2)-like 2- Nrf2 transcriptional pathway, which up-regulates the genes involved in the cellular response to oxidative stress. The drug was evaluated in 2 large, randomized, double-blind, multicentric, multinational, 2-year, phase III clinical trials. The DEFINE and CONFIRM trials, conducted with over 2600 adult patients suffering from RRMS, unequivocally confirmed the efficacy of DMF (2 x 240 mg daily) in reducing the annualized relapse rate (ARR) and reducing the proportion of patients with MS relapse at 2 years. Significantly reduced sustained disability progression was observed with the drug versus placebo in DEFINE, while the same tendency was seen in CONFIRM. The MRI results of the studies were also convincing: DMF significantly reduced the number of new/enlarging T2-hyperintense lesions and the number of Gd-enhancing lesions compared to placebo. Dimethyl fumarate was generally well tolerated and no safety concern has been raised. Adverse events that occurred most frequently included flushing and gastrointestinal events. The long-term efficacy and tolerability of dimethyl fumarate is currently being investigated in the ENDORSE trial, with interim results demonstrating the same results as the two previous studies. In conclusion, although further, mostly comparative data are needed to fully establish the relative efficacy and tolerability of dimethyl fumarate compared with other therapies, dimethyl-fumarate is a valuable addition to the therapeutic options available for RRMS. PMID:25842911

Matolcsi, Judit; Rózsa, Csilla

2015-01-30

100

Ready to Use Therapeutic Foods (RUTF) improves undernutrition among ART-treated, HIV-positive children in Dar es Salaam, Tanzania  

PubMed Central

Background HIV/AIDS is associated with an increased burden of undernutrition among children even under antiretroviral therapy (ART). To treat undernutrition, WHO endorsed the use of Ready to Use Therapeutic Foods (RUTF) that can reduce case fatality and undernutrition among ART-naďve HIV-positive children. However, its effects are not studied among ART-treated, HIV-positive children. Therefore, we examined the association between RUTF use with underweight, wasting, and stunting statuses among ART-treated HIV-positive children in Dar es Salaam, Tanzania. Methods This cross-sectional study was conducted from September-October 2010. The target population was 219 ART-treated, HIV-positive children and the same number of their caregivers. We used questionnaires to measure socio-economic factors, food security, RUTF-use, and ART-duration. Our outcome variables were underweight, wasting, and stunting statuses. Results Of 219 ART-treated, HIV-positive children, 140 (63.9%) had received RUTF intervention prior to the interview. The percentages of underweight and wasting among non-RUTF-receivers were 12.4% and 16.5%; whereas those of RUTF-receivers were 3.0% (P?=?0.006) and 2.8% (P?=?0.001), respectively. RUTF-receivers were less likely to have underweight (Adjusted Odd Ratio (AOR) =0.19, CI: 0.04, 0.78), and wasting (AOR?=?0.24, CI: 0.07, 0.81), compared to non RUTF-receivers. Among RUTF receivers, children treated for at least four months (n?=?84) were less likely to have underweight (P?=?0.049), wasting (P?=?0.049) and stunting (P?HIV-positive children under ART, the provision of RUTF for at least four months was associated with low proportions of undernutrition status. RUTF has a potential to improve undernutrition among HIV-positive children under ART in the clinical settings in Dar es Salaam, Tanzania. PMID:22931107

2012-01-01

101

Local ELF-magnetic field: a possible novel therapeutic approach to psychology symptoms.  

PubMed

The recorded EEG of some brain regions of patients such as attention deficit hyperactivity disorder (ADHD), depression and etc. are different in comparison to healthy people. The disease improves with modifying the patient EEG that this is the basis of neurofeedback training. The main disadvantage of neurofeedback training demands patient's collaborative and active participation during treatment sessions, while some of patients such as addicts, depressed people and ADHD children cannot easily concentrate in direction of therapist's purpose. Furthermore, extremely low frequency magnetic fields (MFs) can affect brain signals and change them that in some cases lead to clinical effects. This report proposes if by locating small coils in desired region proceeds to local exposure of brain and happens in different frequencies or intensities and the effects of each MF in brain signals get analyzed then by knowing its effects we can make changes in patient voluntary without direct participation of patient in his/her brain signal changes. In the other words by changing type of the MF exposure and immediate record of brain signals we can fallow brain signals by observing the immediate record after exposure, with changes in the amplitude and the next exposure frequency, the therapist tries to direct the brain signal of desired region to the purpose. The possibility of approving this hypothesis in spite of contradictory effects about recovery or appearance of depression because of the MF and ability of local magnetic field exposures in changing of brain signals get reinforced to some extent. PMID:25073696

Shafiei, Seyed Ali; Firoozabadi, Seyed Mohammad

2014-11-01

102

Nutrition outcomes of HIV-infected malnourished adults treated with ready-to-use therapeutic food in sub-Saharan Africa: a longitudinal study  

PubMed Central

Background Among people living with HIV/AIDS, nutritional support is increasingly recognized as a critical part of the essential package of care, especially for patients in sub-Saharan Africa. The objectives of the study were to evaluate the outcomes of HIV-positive malnourished adults treated with ready-to-use therapeutic food and to identify factors associated with nutrition programme failure. Methods We present results from a retrospective cohort analysis of patients aged 15 years or older with a body mass index of less than 17 kg/m2 enrolled in three HIV/AIDS care programmes in Africa between March 2006 and August 2008. Factors associated with nutrition programme failure (patients discharged uncured after six or more months of nutritional care, defaulting from nutritional care, remaining in nutritional care for six or more months, or dead) were investigated using multiple logistic regression. Results Overall, 1340 of 8685 (15.4%) HIV-positive adults were enrolled in the nutrition programme. At admission, median body mass index was 15.8 kg/m2 (IQR 14.9-16.4) and 12% received combination antiretroviral therapy (ART). After a median of four months of follow up (IQR 2.2-6.1), 524 of 1106 (47.4%) patients were considered cured. An overall total of 531 of 1106 (48.0%) patients failed nutrition therapy, 132 (11.9%) of whom died and 250 (22.6%) defaulted from care. Men (OR = 1.5, 95% CI 1.2-2.0), patients with severe malnutrition at nutrition programme enrolment (OR = 2.2, 95% CI 1.7-2.8), and those never started on ART (OR = 4.5, 95% CI 2.7-7.7 for those eligible; OR = 1.6, 95% CI 1.0-2.5 for those ineligible for ART at enrolment) were at increased risk of nutrition programme failure. Diagnosed tuberculosis at nutrition programme admission or during follow up, and presence of diarrhoeal disease or extensive candidiasis at admission, were unrelated to nutrition programme failure. Conclusions Concomitant administration of ART and ready-to-use therapeutic food increases the chances of nutritional recovery in these high-risk patients. While adequate nutrition is necessary to treat malnourished HIV patients, development of improved strategies for the management of severely malnourished patients with HIV/AIDS are urgently needed. PMID:21219607

2011-01-01

103

Infection of Female Primary Lower Genital Tract Epithelial Cells after Natural Pseudotyping of HIV-1: Possible Implications for Sexual Transmission of HIV-1  

PubMed Central

The global AIDS pandemic continues to expand and in some regions of the world, such as southern Africa, the prevalence of HIV-1 infection exceeds 20%. The devastating spread of the virus in young women in these countries appears disproportional to overall risk of infection. Regions with high prevalence of HIV-1 are often also highly endemic for other pathogenic viruses including HSV, CMV and HTLV. We propose that acquisition by HIV-1 of the envelope glycoproteins of other viruses, in a process we call “natural pseudotyping,” expands the cellular tropism of HIV-1, enabling it to infect female genital epithelial cells directly and thereby dramatically increasing risk of infection during sexual intercourse. In this proof-of-concept study, we demonstrate that when HIV-1 co-infects T cells along with the gammaretrovirus xenotropic murine leukemia virus-related virus (XMRV), progeny HIV-1 particles are produced capable of infecting primary vaginal, ectocervical and endocervical epithelial cells. These cell types are normally resistant to HIV-1 infection. Infection of primary genital cells was neutralized by antisera against the XMRV glycoprotein, confirming that infection was mediated by the XMRV glycoprotein acquired through pseudotyping of HIV. Inhibition by AZT showed that active replication of HIV-1 occurred in these cells and ruled out non-specific endocytic uptake of the virus. These results demonstrate that natural pseudotyping can expand the tropism of HIV-1 to include genital epithelial cells and have potential implications for sexual transmission of the virus. PMID:25010677

Tang, Yuyang; George, Alvin; Nouvet, Franklin; Sweet, Stephanie; Emeagwali, Nkiruka; Taylor, Harry E.; Simmons, Glenn; Hildreth, James E. K.

2014-01-01

104

Therapeutic DNA Vaccination of Vertically HIV-Infected Children: Report of the First Pediatric Randomised Trial (PEDVAC)  

PubMed Central

Subjects Twenty vertically HIV-infected children, 6–16 years of age, with stable viral load control and CD4+ values above 400 cells/mm3. Intervention Ten subjects continued their ongoing antiretroviral treatment (ART, Group A) and 10 were immunized with a HIV-DNA vaccine in addition to their previous therapy (ART and vaccine, Group B). The genetic vaccine represented HIV-1 subtypes A, B and C, encoded Env, Rev, Gag and RT and had no additional adjuvant. Immunizations took place at weeks 0, 4 and 12, with a boosting dose at week 36. Monitoring was performed until week 60 and extended to week 96. Results Safety data showed good tolerance of the vaccine. Adherence to ART remained high and persistent during the study and did not differ significantly between controls and vaccinees. Neither group experienced either virological failure or a decline of CD4+ counts from baseline. Higher HIV-specific cellular immune responses were noted transiently to Gag but not to other components of the vaccine. Lymphoproliferative responses to a virion antigen HIV-1 MN were higher in the vaccinees than in the controls (p?=?0.047), whereas differences in reactivity to clade-specific Gag p24, RT or Env did not reach significance. Compared to baseline, the percentage of HIV-specific CD8+ lymphocytes releasing perforin in the Group B was higher after the vaccination schedule had been completed (p?=?0.031). No increased CD8+ perforin levels were observed in control Group A. Conclusions The present study demonstrates the feasibility, safety and moderate immunogenicity of genetic vaccination in vertically HIV-infected children, paving the way for amplified immunotherapeutic approaches in the pediatric population. Trial registration clinicaltrialsregister.eu _2007-002359-18IT PMID:24312194

Palma, Paolo; Romiti, Maria Luisa; Montesano, Carla; Santilli, Veronica; Mora, Nadia; Aquilani, Angela; Dispinseri, Stefania; Tchidjou, Hyppolite K.; Montano, Marco; Eriksson, Lars E.; Baldassari, Stefania; Bernardi, Stefania; Scarlatti, Gabriella

2013-01-01

105

HIV chemotherapy  

NASA Astrophysics Data System (ADS)

The use of chemotherapy to suppress replication of the human immunodeficiency virus (HIV) has transformed the face of AIDS in the developed world. Pronounced reductions in illness and death have been achieved and healthcare utilization has diminished. HIV therapy has also provided many new insights into the pathogenesis and the viral and cellular dynamics of HIV infection. But challenges remain. Treatment does not suppress HIV replication in all patients, and the emergence of drug-resistant virus hinders subsequent treatment. Chronic therapy can also result in toxicity. These challenges prompt the search for new drugs and new therapeutic strategies to control chronic viral replication.

Richman, Douglas D.

2001-04-01

106

Humanized Mouse Models of HIV Infection  

PubMed Central

Because of the limited tropism of HIV, in vivo modeling of this virus has been almost exclusively limited to other lentiviruses such as SIV that reproduce many important characteristics of HIV infection. However, there are significant genetic and biological differences among lentiviruses and some HIV-specific interventions are not effective against other lentiviruses in non-human hosts. For these reasons much emphasis has recently been placed on developing alternative animal models that support HIV replication and recapitulate key aspects of HIV infection and pathogenesis in humans. Humanized mice, CD34+ hematopoietic progenitor cell transplanted immunodeficient mice and in particular mice also implanted with human thymic/liver tissue (BLT mice) that develop a functional human immune system, have been the focus of a great deal of attention as possible models to study virtually all aspects of HIV biology and pathogenesis. Humanized mice are systemically reconstituted with human lymphoid cells offering rapid, reliable and reproducible experimental systems for HIV research. Peripheral blood of humanized mice can be readily sampled longitudinally to assess reconstitution with human cells and to monitor HIV replication permitting the evaluation of multiple parameters of HIV infection such as viral load levels, CD4+ T cell depletion, immune activation, as well as the effects of therapeutic interventions. Of high relevance to HIV transmission is the extensive characterization and validation of the reconstitution with human lymphoid cells of the female reproductive tract and of the gastrointestinal tract of humanized BLT mice that renders them susceptible to both vaginal and rectal HIV infection. Other important attributes of all types of humanized mice include: 1) their small size and cost that make them broadly accessible; 2) multiple cohorts of humanized mice can be made from multiple human donors and each cohort has identical human cells, permitting control of intragenetic variables; 3) continuous de novo production of human immune cells from the transplanted CD34+ cells within each humanized mouse facilitates long term experiments; 4) both primary and laboratory HIV isolates can be used for experiments; and 5) in addition to therapeutic interventions, rectal and vaginal HIV prevention approaches can be studied. In summary, humanized mice can have an important role in virtually all aspects of HIV research including the analysis of HIV replication, the evaluation of HIV restriction factors, the characterization of successful biomedical HIV prevention strategies, the evaluation of new treatment regimens and the evaluation of novel HIV eradication strategies. PMID:21799532

Denton, Paul W.; Garcia, J. Victor

2013-01-01

107

Blocking Type I Interferon Production: A New Therapeutic Option to Reduce the HIV-1-Induced Immune Activation  

PubMed Central

Highly active antiretroviral therapy has dramatically improved the morbidity and mortality of HIV-1-infected individuals. A total of 25 licensed drugs provide the basis for an optimized virus-suppressive treatment of nearly each subject. The promises of immune reconstitution and normal life expectancy, however, fall short for a number of patients, either through inadequate recovery of CD4+ T-cell counts or the occurrence of non-AIDS defining malignancies. In this respect, the prevalence of Epstein-Barr virus-associated Hodgkin lymphoma and human papillomavirus-related anal neoplasia is rising in aging HIV-1-infected individuals despite antiretroviral therapy. An important cause appears to be the HIV-1-induced chronic immune activation, propagated by inappropriate release of proinflammatory cytokines and type I interferons. This immune dysregulation can be reduced in vitro by inhibitors blocking the endosomal acidification. Recent data suggest that this concept is also of relevance in vivo, which opens the door for adjuvant immunomodulatory therapies in HIV-1 infection. PMID:22203858

Ries, Moritz; Pritschet, Kathrin; Schmidt, Barbara

2012-01-01

108

Possible Prognostic and Therapeutic Significance of c-Kit Expression, Mast Cell Count and Microvessel Density in Renal Cell Carcinoma  

PubMed Central

Renal cell carcinoma (RCC) is the most frequent renal tumor and its incidence is increasing worldwide. Tumor angiogenesis is known to play a crucial role in the etiopathogenesis of RCC and over the last few years an even deeper knowledge of its contribution in metastatic RCC development has led to the development of numerous molecular targeting agents (such as sunitinib, sorafenib, pazopanib, axitinib, tivozanib, and dovitinib). The above agents are principally directed against vascular endothelial growth factor receptor (VEGFR) members and also against c-Kit receptor (c-KitR). The role of c-kitR inhibition on clear cell RCC (ccRCC), the main RCC subtype, is less well established. Whether c-kitR activation through its ligand, stem cell factor (SCF) contributes significantly to the effects of tyrosine kinase inhibitors (TKIs) treatment remains to be established. It is important to underscore that the c-KitR is expressed on mast cells (MCs) and cancer cells. After an examination of the c-KitR/SCF pathway, we review here the principal studies that have evaluated c-Kit expression in RCC. Moreover, we summarize some investigations that have observed the distribution of MCs in primary renal cancer and in adjacent normal tissue with appropriate histological immunohistochemical techniques. We also focus on few studies that have evaluated the correlation between RCC proliferation, MC count and microvessel density (MVD), as hallmarks of tumor angiogenesis. Thus, the aim of this review of the literature is to clarify if c-KitR expression, MC count and MVD could have prognostic significance and the possible predictive therapeutic implications in RCC. PMID:25056544

Marech, Ilaria; Gadaleta, Cosmo Damiano; Ranieri, Girolamo

2014-01-01

109

A Low-Molecular-Weight Compound K7174 Represses Hepcidin: Possible Therapeutic Strategy against Anemia of Chronic Disease  

PubMed Central

Hepcidin is the principal iron regulatory hormone, controlling the systemic absorption and remobilization of iron from intracellular stores. The expression of the hepcidin gene, HAMP, is increased in patients with anemia of chronic disease. Previously, the synthetic compound K7174 was identified through chemical screening as a novel inhibitor of the adhesion of monocytes to cytokine-stimulated endothelial cells. K7174 also ameliorated anemia induced by inflammatory cytokines in mice, which suggests a possible involvement of hepcidin regulation. The present study was performed to assess the impact of K7174 on hepcidin expression in a human hematoma cell line and in mice in vivo. We first demonstrated that K7174 treatment in HepG2 cells significantly decreased HAMP expression. Then, we conducted microarray analysis to determine the molecular mechanism by which K7174 inhibits HAMP expression. Transcriptional profiling confirmed the downregulation of HAMP. Surprisingly, we found that K7174 strongly induced GDF15, known as a negative regulator of HAMP expression. Western blotting analysis as well as ELISA confirmed the induction of GDF15 by K7174 treatment. Furthermore, K7174-mediated HAMP suppression was rescued by the silencing of GDF15 expression. Interestingly, we found that K7174 also upregulates CEBPB. Promoter analysis and chromatin immunoprecipitation analysis revealed that CEBPB could contribute to K7174-mediated transcriptional activation of GDF15. Subsequently, we also examined whether K7174 inhibits hepcidin expression in mice. Quantitative RT-PCR analysis with liver samples from K7174-treated mice demonstrated significant upregulation of Gdf15 and downregulation of Hamp expression, as compared to control mice. Furthermore, serum hepcidin concentration was also significantly decreased in K7174-treated mice. In conclusion, K7174 inhibits hepcidin expression partly by inducing GDF15. K-7174 may be a potential therapeutic option to treat anemia of chronic disease. PMID:24086573

Fujiwara, Tohru; Ikeda, Takashi; Nagasaka, Yuki; Okitsu, Yoko; Katsuoka, Yuna; Fukuhara, Noriko; Onishi, Yasushi; Ishizawa, Kenichi; Ichinohasama, Ryo; Tomosugi, Naohisa; Harigae, Hideo

2013-01-01

110

HIV and the Gut Microbiota, Partners in Crime: Breaking the Vicious Cycle to Unearth New Therapeutic Targets  

PubMed Central

The gut microbiota plays a key role in health and immune system education and surveillance. The delicate balance between microbial growth and containment is controlled by the immune system. However, this balance is disrupted in cases of chronic viral infections such as HIV. This virus is capable of drastically altering the immune system and gastrointestinal environment leading to significant changes to the gut microbiota and mucosal permeability resulting in microbial translocation from the gut into the peripheral blood. The changes made locally in the gut have far-reaching consequences on the other organs of the body starting in the liver, where microbes and their products are normally filtered out, and extending to the blood and even brain. Microbial translocation and their downstream effects such as increased indolamine 2,3-dioxygenase (IDO) enzyme expression and activity create a self-sustaining feedback loop which enhances HIV disease progression and constitute a vicious cycle of inflammation and immune activation combining viral and bacterial factors. Understanding this self-perpetuating cycle could be a key element in developing new therapies aimed at the gut microbiota and its fallout after infection.

Jenabian, Mohammad-Ali

2015-01-01

111

Lessons Learned from HIV Vaccine Clinical Efficacy Trials  

PubMed Central

The past few years have witnessed many promising advances in HIV prevention strategies involving pre-exposure prophylaxis approaches. Some may now wonder whether an HIV vaccine is still needed, and whether developing one is even possible. The partial efficacy reported in the RV144 trial and the encouraging results of the accompanying immune correlates analysis suggest that an effective HIV vaccine is achievable. These successes have provided a large impetus and guidance for conducting more HIV vaccine trials. A key lesson learned from RV144 is that assessment of HIV acquisition is now a feasible and valuable primary objective for HIV preventive vaccine trials. In this article we review how RV144 and other HIV vaccine efficacy trials have instructed the field and highlight some of the HIV vaccine concepts in clinical development. After a long and significant investment, HIV vaccine clinical research is paying off in the form of valuable lessons that, if applied effectively, will accelerate the path toward a safe and effective vaccine. Together with other HIV prevention approaches, preventive and therapeutic HIV vaccines will be invaluable tools in bringing the epidemic to an end. PMID:24033299

Day, Tracey A.; Kublin, James G.

2014-01-01

112

Which Antibody Functions are Important for an HIV Vaccine?  

PubMed Central

HIV antibody (Ab) functions capable of preventing mucosal cell-free or cell-to-cell HIV transmission are critical for the development of effective prophylactic and therapeutic vaccines. In addition to CD4+ T cells, other potential HIV-target cell types including antigen-presenting cells (APCs) (dendritic cells, macrophages) residing at mucosal sites are infected. Moreover, the interactions between APCs and HIV lead to HIV cell-to-cell transmission. Recently discovered broadly neutralizing antibodies (NAbs) are able to neutralize a broad spectrum of HIV strains, inhibit cell-to-cell transfer, and efficiently protect from infection in the experimentally challenged macaque model. However, the 31% protection observed in the RV144 vaccine trial in the absence of detectable NAbs in blood samples pointed to the possible role of additional Ab inhibitory functions. Increasing evidence suggests that IgG Fc? receptor (Fc?R)-mediated inhibition of Abs present at the mucosal site may play a role in protection against HIV mucosal transmission. Moreover, mucosal IgA Abs may be determinant in protection against HIV sexual transmission. Therefore, defining Ab inhibitory functions that could lead to protection is critical for further HIV vaccine design. Here, we review different inhibitory properties of HIV-specific Abs and discuss their potential role in protection against HIV sexual transmission. PMID:24995008

Su, Bin; Moog, Christiane

2014-01-01

113

Growth and trophic factors, pH and the Na+/H+ exchanger in Alzheimer's disease, other neurodegenerative diseases and cancer: new therapeutic possibilities and potential dangers.  

PubMed

Abnormalities in the intricate intracellular signalling pathways play a key role in the deregulation of either spontaneous (normal or pathological) or induced (therapeutic) cell death mechanisms. Some of these pathways are increasingly becoming molecular therapeutic targets in different processes, ranging from neurodegenerative diseases to cancer. Recent discoveries in research and treatment have shown that failure to induce selective cell apoptosis in hyperproliferative processes, like neoplastic diseases, and the failure to prevent spontaneous cell death in neurodegenerative diseases (HNDDs) such as Alzheimer's disease (AD), multiple sclerosis (MS), amyothrophic lateral sclerosis (ALS), Huntington's disease (HD), and retinitis pigmentosa (RP), can be interpreted as problems stemming from the same basic mechanisms but moving in diametrically opposed directions. The integrated approach advanced here represents an interdisciplinary attempt to stimulate an integrated vision of two otherwise widely separated areas of research, experimental neurology and oncology. This kind of approach to the prevention of apoptosis (therapeutic antiapoptosis) and/or other forms of cell death in HNNDs, as well as to resistance to therapeutic apoptosis in cancer (pathological antiapoptosis), has the scope to improve the understanding of the dualistic nature of the basic abnormalities underlying the pathological deregulation of cell death. In this context, an intracellular pH (pH(i))-related approach to these opposed situations is advanced to provide a unified theory of the apoptosis-antiapoptosis machinery. Some potential therapeutic possibilities opened by these lines of research, regarding the utilization of human growth factors and/or cellular anti-acidification measures directed to sustain cellular acid-base homeostasis in different HNNDs are considered because of their potential therapeutic benefit. Finally, we advance some possible dangers and side-effects raised by these very same treatment efforts. PMID:17316166

Harguindey, Salvador; Reshkin, Stephan J; Orive, Gorka; Arranz, Jose Luis; Anitua, Eduardo

2007-02-01

114

Aging and HIV Infection  

PubMed Central

With the advent of highly active antiretroviral therapy (HAART) in mid-1995, the prognosis for HIV-infected individuals has brightened dramatically. However, the conjunction of potent antiviral therapy and longer life expectancy may engender a variety of health risks that, heretofore, HIV specialists have not had to confront. The long-term effects of HIV infection itself and exposure to antiretroviral agents is unknown. Several aspects of aging, including psychiatric disease, neurocognitive impairment, and metabolic and hormonal disorders, may be influenced by chronic exposure to HIV and/or HIV therapeutics. In this paper, we discuss the health issues confronting HIV-infected older adults and areas for future research. PMID:16736353

Klein, Robert S.; Schoenbaum, Ellie E.; Anastos, Kathryn; Minkoff, Howard; Sacks, Henry S.

2006-01-01

115

Use of a Rapid HIV Home Test to Screen Sexual Partners: An Evaluation of Its Possible Use and Relative Risk  

PubMed Central

We estimated the HIV risk reduction that could be attained by using a rapid HIV home test (HT) to screen sexual partners versus using condoms in different proportions of anal intercourse (AI) occasions among men who have sex with men (MSM). Special attention was paid to the role of the window period during which infected cases go undetected. Our results show that if MSM engage in AI without condoms following a non-reactive HT result, they have lower chances of becoming infected by someone still in the window period than by following heuristics and using condoms inconsistently. For MSM who do not use condoms, use of HT as a screening device may be a useful risk reduction strategy. This advantage increases with higher HIV population prevalence. With higher HIV incidence, this strategy will not provide any advantage if condoms are used in as little as one out of four occasions. PMID:19415483

Ventuneac, Ana; Carballo-Diéguez, Alex; Leu, Cheng-Shiun; Levin, Bruce; Bauermeister, Jose; Woodman-Maynard, Emily; Giguere, Rebecca

2009-01-01

116

Therapeutic Immunization with HIV-1 Tat Reduces Immune Activation and Loss of Regulatory T-Cells and Improves Immune Function in Subjects on HAART  

PubMed Central

Although HAART suppresses HIV replication, it is often unable to restore immune homeostasis. Consequently, non-AIDS-defining diseases are increasingly seen in treated individuals. This is attributed to persistent virus expression in reservoirs and to cell activation. Of note, in CD4+ T cells and monocyte-macrophages of virologically-suppressed individuals, there is continued expression of multi-spliced transcripts encoding HIV regulatory proteins. Among them, Tat is essential for virus gene expression and replication, either in primary infection or for virus reactivation during HAART, when Tat is expressed, released extracellularly and exerts, on both the virus and the immune system, effects that contribute to disease maintenance. Here we report results of an ad hoc exploratory interim analysis (up to 48 weeks) on 87 virologically-suppressed HAART-treated individuals enrolled in a phase II randomized open-label multicentric clinical trial of therapeutic immunization with Tat (ISS T-002). Eighty-eight virologically-suppressed HAART-treated individuals, enrolled in a parallel prospective observational study at the same sites (ISS OBS T-002), served for intergroup comparison. Immunization with Tat was safe, induced durable immune responses, and modified the pattern of CD4+ and CD8+ cellular activation (CD38 and HLA-DR) together with reduction of biochemical activation markers and persistent increases of regulatory T cells. This was accompanied by a progressive increment of CD4+ T cells and B cells with reduction of CD8+ T cells and NK cells, which were independent from the type of antiretroviral regimen. Increase in central and effector memory and reduction in terminally-differentiated effector memory CD4+ and CD8+ T cells were accompanied by increases of CD4+ and CD8+ T cell responses against Env and recall antigens. Of note, more immune-compromised individuals experienced greater therapeutic effects. In contrast, these changes were opposite, absent or partial in the OBS population. These findings support the use of Tat immunization to intensify HAART efficacy and to restore immune homeostasis. Trial registration ClinicalTrials.gov NCT00751595 PMID:21085635

Ensoli, Barbara; Bellino, Stefania; Tripiciano, Antonella; Longo, Olimpia; Francavilla, Vittorio; Marcotullio, Simone; Cafaro, Aurelio; Picconi, Orietta; Paniccia, Giovanni; Scoglio, Arianna; Arancio, Angela; Ariola, Cristina; Ruiz Alvarez, Maria J.; Campagna, Massimo; Scaramuzzi, Donato; Iori, Cristina; Esposito, Roberto; Mussini, Cristina; Ghinelli, Florio; Sighinolfi, Laura; Palamara, Guido; Latini, Alessandra; Angarano, Gioacchino; Ladisa, Nicoletta; Soscia, Fabrizio; Mercurio, Vito S.; Lazzarin, Adriano; Tambussi, Giuseppe; Visintini, Raffaele; Mazzotta, Francesco; Di Pietro, Massimo; Galli, Massimo; Rusconi, Stefano; Carosi, Giampiero; Torti, Carlo; Di Perri, Giovanni; Bonora, Stefano; Ensoli, Fabrizio; Garaci, Enrico

2010-01-01

117

CXCL12/CXCR4 axis in the pathogenesis of acute lymphoblastic leukemia (ALL): a possible therapeutic target.  

PubMed

Acute lymphoblastic leukemia (ALL) is the commonest childhood malignancy, accounting for approximately 80 % of leukemia in the pediatric group, and its etiology is unknown. This neoplasia is characterized by male predominance, high-risk features and poor outcome, mainly in recurrence patients and adults. In recent years, advances in the success of childhood ALL treatment were verified, and the rate of cure is over 80 % of individuals. However, there is a considerable scope for improving therapeutic outcome in this neoplasia. Improvements in ALL therapy might readily be achieved by developing additional biomarkers that can predict and refine prognosis in patients with ALL. In normal hematopoietic cells, cytokines provide the stimulus for proliferation, survival, self-renewal, differentiation and functional activation. Abnormalities of cytokines are characteristic in all forms of leukemia, including ALL. The stromal cell-derived factor-1 (SDF-1 or CXCL12) is a member of the CXC chemokine family that binds to CXC chemokine receptor 4 (CXCR4). The CXCL12/CXCR4 axis appears to play a role in dissemination of solid tumors and hematopoietic diseases. Understanding the mechanisms by which ALL cells are disseminated will provide additional information to expand therapeutic approach. Therefore, this review summarizes information relating to ALL cell biology, focusing specifically in a cytokine receptor important axis, CXCL12/CXCR4, that may have implications for novel treatment strategies to improve life expectancy of patients with this neoplasia. PMID:25572297

de Lourdes Perim, Aparecida; Amarante, Marla Karine; Guembarovski, Roberta Losi; de Oliveira, Carlos Eduardo Coral; Watanabe, Maria Angelica Ehara

2015-05-01

118

Restricting HIV-1 pathways for escape using rationally designed anti–HIV-1 antibodies  

PubMed Central

Recently identified broadly neutralizing antibodies (bNAbs) that potently neutralize most HIV-1 strains are key to potential antibody-based therapeutic approaches to combat HIV/AIDS in the absence of an effective vaccine. Increasing bNAb potencies and resistance to common routes of HIV-1 escape through mutation would facilitate their use as therapeutics. We previously used structure-based design to create the bNAb NIH45-46G54W, which exhibits superior potency and/or breadth compared with other bNAbs. We report new, more effective NIH45-46G54W variants designed using analyses of the NIH45-46–gp120 complex structure and sequences of NIH45-46G54W–resistant HIV-1 strains. One variant, 45-46m2, neutralizes 96% of HIV-1 strains in a cross-clade panel and viruses isolated from an HIV-infected individual that are resistant to all other known bNAbs, making it the single most broad and potent anti–HIV-1 antibody to date. A description of its mechanism is presented based on a 45-46m2–gp120 crystal structure. A second variant, 45-46m7, designed to thwart HIV-1 resistance to NIH45-46G54W arising from mutations in a gp120 consensus sequence, targets a common route of HIV-1 escape. In combination, 45-46m2 and 45-46m7 reduce the possible routes for the evolution of fit viral escape mutants in HIV-1YU-2–infected humanized mice, with viremic control exhibited when a third antibody, 10–1074, was added to the combination. PMID:23712429

Klein, Florian; Horwitz, Joshua A.; Halper-Stromberg, Ariel; Sather, D. Noah; Marcovecchio, Paola M.; Lee, Terri; West, Anthony P.; Gao, Han; Seaman, Michael S.; Stamatatos, Leonidas; Nussenzweig, Michel C.; Bjorkman, Pamela J.

2013-01-01

119

Small molecule inducers of heat-shock response reduce polyQ-mediated huntingtin aggregation. A possible therapeutic strategy.  

PubMed

Enhancing cellular defense mechanisms against different kinds of stress may be an attractive therapeutic strategy for neurodegenerative diseases. In particular, inducing the expression of molecular chaperones might reduce the formation of misfolded proteins and toxic aggregates that occur in polyglutamine (polyQ) disorders such as Huntington's disease. Geldanamycin, a natural substance that modulates Hsp90 function, was previously shown to induce a heat-shock response and to reduce polyQ aggregation in mammalian cells. However, because of toxic and unfavorable pharmacokinetic properties, geldanamycin is not suitable for clinical use. In this study we evaluated the effects of the pharmacologically improved geldanamycin derivatives 17-DMAG and 17-AAG on polyQ aggregation in mammalian cells. Quantitative RT-PCR and SDS-PAGE experiments revealed that 17-DMAG induces expression of the molecular chaperones Hsp40, Hsp70, and Hsp105 in mammalian cells and inhibits the formation of mutant huntingtin aggregates with higher efficiency than 17-AAG or geldanamycin itself. Induction of a heat-shock response and inhibition of polyQ aggregation occurred at nanomolar concentrations. We suggest that geldanamycin derivatives such as 17-DMAG should be considered for the development of a drug treatment for polyQ disorders and other neurodegenerative diseases involving protein aggregation. PMID:17596719

Herbst, Martin; Wanker, Erich E

2007-01-01

120

Protein misdirection inside and outside motor neurons in Amyotrophic Lateral Sclerosis (ALS): a possible clue for therapeutic strategies.  

PubMed

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by progressive muscle wasting and weakness with no effective cure. Emerging evidence supports the notion that the abnormal conformations of ALS-linked proteins play a central role in triggering the motor neuron degeneration. In particular, mutant types of superoxide dismutase 1 (SOD1) and TAR DNA binding protein 43kDa (TDP-43) are key molecules involved in the pathogenesis of familial and sporadic ALS, respectively. The commonalities of the two proteins include a propensity to aggregate and acquire detrimental conformations through oligomerization, fragmentation, or post-translational modification that may drive abnormal subcellular localizations. Although SOD1 is a major cytosolic protein, mutated SOD1 has been localized to mitochondria, endoplasmic reticulum, and even the extracellular space. The nuclear exclusion of TDP-43 is a pathological hallmark for ALS, although the pathogenic priority remains elusive. Nevertheless, these abnormal behaviors based on the protein misfolding are believed to induce diverse intracellular and extracellular events that may be tightly linked to non-cell-autonomous motor neuron death. The generation of mutant- or misfolded protein-specific antibodies would help to uncover the distribution and propagation of the ALS-linked proteins, and to design a therapeutic strategy to clear such species. Herein we review the literature regarding the mislocalization of ALS-linked proteins, especially mutant SOD1 and TDP-43 species, and discuss the rationale of molecular targeting strategies including immunotherapy. PMID:22072931

Ido, Akemi; Fukuyama, Hidenao; Urushitani, Makoto

2011-01-01

121

Structural and electronic properties of new fullerene derivatives and their possible application as HIV-1 protease inhibitors  

NASA Astrophysics Data System (ADS)

Density functional theory (DFT) calculations have been carried out at the hybrid Becke 3-Lee-Yang-Parr; B3LYP/3-21G** level of theory to study two series of hydroxy-chalca-acetic acid-(4-pyrrolidin-1-yl-phenyl) ester [C 60-C 2H 4N-(4-XCOCH 2OH)C 6H 4] and hydroxy-chalcoacetic acid-[2-(2-hydroxy-acetylchalcanyl)-4-pyrrolidin-1-yl-phenyl] ester[C 60-C 2H 4N-(3,4-XCOCH 2OH)C 6H 4]. The X atom is O, S or Se for the two series. The vibrational spectra, physical, chemical, thermodynamics and Quantitative Structure Activity Relationship (QSAR) properties of the studied molecules are calculated and discussed. We have evaluated these molecules as HIV-1 protease inhibitors based on the hydrogenation interaction between the hydroxymethylcarbonyl (HMC) groups and the two aspartic acid of the HIV-1 protease active site. Results show that some of the investigated fullerene-based derivatives can be considered promising as HIV-1 protease inhibitors.

Ibrahim, Medhat; Saleh, Noha A.; Hameed, Ali Jameel; Elshemey, Wael M.; Elsayed, Anwar A.

2010-02-01

122

Schizotypy and leadership: a contrasting model for deficit symptoms, and a possible therapeutic role for sex hormones.  

PubMed

Associational loosening, slow and faulty information processing, poor gating of irrelevant stimuli, poor ability to shift attention, poor working memory, passivity, ambivalence, anhedonia, and impaired motor coordination are cardinal features of schizophrenia but, unlike delusions and hallucinations, they are related more to negative/deficit symptoms. As summarized by Bass, numerous studies have correlated leadership with 'ambition, initiative and persistence' (opposite of passivity), 'speed and accuracy of thought', 'finality of decision,' or decisiveness (the opposite of ambivalence), 'mood control, optimism and sense of humor' (opposite of anhedonia), etc. Andreasen et al postulate that a disruption in the circuitry among nodes located in the prefrontal regions, the thalamic nuclei, and the cerebellum produces 'cognitive dysmetria', meaning difficulty in prioritizing, coordinating, and responding to information, and that it can account for the broad diversity of symptoms of schizophrenia. A relationship between cognitive processes and cerebellar and basal ganglia functions, and a role of neocerebellum in rapidly shifting attention, have been demonstrated. The cognitive styles, including a proficiency to quickly shift attention, of several famous leaders are used as examples of this contrasting model. Julius Caesar and Napoleon, for instance, could dictate to up to six secretaries simultaneously, using their exceptional working memories, and proficiency in quickly and effortlessly shifting attention while flawlessly gating irrelevant external and internal stimuli. It is suggested that specific brain imaging studies could illustrate this contrast. Gray et al noted positive correlations between 'dominance', an important leadership trait, and serum levels of dehydroepiandrosterone (DHEA) and testosterone (T), but not of more potent dihydrotestosterone (DHT), in over 1700 older men. Though not scientifically rigorous, the author noted positive correlations (P = 0.0162) between the self-rated ratings of voice depth (promoted by T) and of leadership, but none between those of body hair (DHT dependent) and of leadership in 47 male US National Academy of Sciences members. And 43 male US Senators had deeper voices than 36 male House members (P<0.01) who, in turn, had deeper voices than either of two groups (numbers 102 and 72) of male scientists (P<0.01). Therapeutically, before chlorpromazine, DHEA had been used in young schizophrenics with modest success in improving deficit symptoms. DHEA, or other sex hormones, or some of their natural and synthetic derivatives may prove to be valuable to treat deficit symptoms of schizophrenia in both sexes. PMID:10859637

Alias, A G

2000-04-01

123

Treatment of Dyslipidemia in HIV.  

PubMed

Patients infected with HIV have a high risk of developing dyslipidemia. Effective therapeutic strategies can be challenging due to an increase risk of drug interactions and other comorbidities. Understanding the underlying pathophysiology and the principles of pharmacological and non-pharmacological therapeutic interventions can be of value in the appropriate management of dyslipidemia in the HIV-infected patient. PMID:25702057

Sekhar, Rajagopal V

2015-04-01

124

Increasing Obesity in Treated Female HIV Patients from Sub-Saharan Africa: Potential Causes and Possible Targets for Intervention  

PubMed Central

Objectives: To investigate changing nutritional demographics of treated HIV-1-infected patients and explore causes of obesity, particularly in women of African origin. Methods: We prospectively reviewed nutritional demographics of clinic attenders at an urban European HIV clinic during four one-month periods at three-yearly intervals (2001, 2004, 2007, and 2010) and in two consecutive whole-year reviews (2010–2011 and 2011–2012). Risk-factors for obesity were assessed by multiple linear regression. A sub-study of 50 HIV-positive African female patients investigated body-size/shape perception using numerical, verbal, and pictorial cues. Results: We found a dramatic rise in the prevalence of obesity (BMI?>?30?kg/m2), from 8.5 (2001) to 28% (2011–2012) for all clinic attenders, of whom 86% were on antiretroviral treatment. Women of African origin were most affected, 49% being obese, with a further 32% overweight (BMI 25–30?kg/m2) in 2012. Clinical factors strongly associated with obesity included female gender, black African ethnicity, non-smoking, age, and CD4 count (all P?

McCormick, Claire L.; Francis, Arianne M.; Iliffe, Kim; Webb, Helen; Douch, Catherine J.; Pakianathan, Mark; Macallan, Derek C.

2014-01-01

125

Intranasal Administration of a Therapeutic HIV Vaccine (Vacc-4x) Induces Dose-Dependent Systemic and Mucosal Immune Responses in a Randomized Controlled Trial  

PubMed Central

Background Vacc-4x, a Gag p24-based therapeutic HIV vaccine, has been shown to reduce viral load set-points after intradermal administration. In this randomized controlled pilot study we investigate intranasal administration of Vacc-4x with Endocine as adjuvant. Methods Safety and immunogenicity were tested in patients on effective ART. They were randomized to low, medium or high dose Vacc-4x or adjuvant alone, administered four times at weekly intervals with no booster. Vacc-4x-specific T cell responses were measured in vitro by proliferation and in vivo by a single DTH skin test at the end of study. Nasal and rectal mucosal secretions were analyzed for Vacc-4x-specific antibodies by ELISA. Immune regulation induced by Vacc-4x was assessed by functional blockade of the regulatory cytokines IL-10 and TGF-?. Results Vacc-4x proliferative T cell responses increased only among the vaccinated (p?0.031). The low dose group showed the greatest increase in Vacc-4x CD8+T cell responses (p?=?0.037) and developed larger DTH (p?=?0.005) than the adjuvant group. Rectal (distal) Vacc-4x IgA and IgG antibodies also increased (p?=?0.043) in this group. In contrast, the high dose generated higher nasal (local) Vacc-4x IgA (p?=?0.028) and serum IgG (p?=?0.030) antibodies than the adjuvant. Irrespective of dose, increased Vacc-4x CD4+T cell responses were associated with low proliferation (r?=??0.82, p<0.001) and high regulation (r?=?0.61, p?=?0.010) at baseline. Conclusion Intranasal administration of Vacc-4x with Endocine was safe and induced dose-dependent vaccine-specific T cell responses and both mucosal and systemic humoral responses. The clinical significance of dose, immune regulation and mucosal immunity warrants further investigation. Trial Registration ClinicalTrials.gov NCT01473810 PMID:25398137

Brekke, Kristin; Lind, Andreas; Holm-Hansen, Carol; Haugen, Inger Lise; Sřrensen, Birger; Sommerfelt, Maja; Kvale, Dag

2014-01-01

126

A Transactional Ecosystems Framework of HIV Positive Fathers' Perceptions of their Children's Psychosocial and Health Needs: Implications for Family and School-Focused Therapeutic Interventions for Children Affected by HIV  

Microsoft Academic Search

The current doctoral project analyzed archival data from a larger NIMH-funded study, entitled the Family Access to Care Study (FACS), to examine a subsample of its participants, in order to determine links between ecosystems affecting HIV-positive fathers and their concerns regarding factors affecting their children. A sub-sample of 143 HIV+ fathers, mostly of African American descent was examined, from the

Soye Zaid-Muhammad

2010-01-01

127

Biometrics . Author manuscript Maximum likelihood estimation of long-term HIV dynamic models and  

E-print Network

; Model selection MESH Keywords Algorithms ; Anti-HIV Agents ; therapeutic use ; Computer Simulation ; HIV Infections ; drug therapy ; epidemiology ; Humans ; Likelihood Functions ; Models, Biological ; Models

Paris-Sud XI, Université de

128

Clinical performance of the Multispot HIV-1/HIV-2 rapid test to correctly differentiate HIV-2 from HIV-1 infection in screening algorithms using third and fourth generation assays and to identify cross reactivity with the HIV-1 Western Blot  

PubMed Central

Background An accurate and rapid serologic method to differentiate HIV-2 from HIV-1 infection is required since the confirmatory HIV-1 Western Blot (WB) may demonstrate cross-reactivity with HIV-2 antibodies. Objectives To evaluate the performance of the Bio-Rad Multispot HIV-1/HIV-2 rapid assay as a supplemental test to correctly identify HIV-2 infection and identify HIV-1 WB cross-reactivity with HIV-2 in clinical samples tested at an academic medical center. Study design Between August 2008 and July 2012, clinical samples were screened for HIV using either 3rd-or 4th-generation HIV-1/2 antibody or combination antibody and HIV-1 p24 antigen assays, respectively. All repeatedly reactive samples were reflexed for Multispot rapid testing. Multispot HIV-2 and HIV-1 and HIV-2-reactive samples were further tested using an HIV-2 immunoblot assay and HIV-1 or HIV-2 RNA assays when possible. The HIV-1 WB was performed routinely for additional confirmation and to assess for HIV-2 antibody cross-reactivity. Results Of 46,061 samples screened, 890 (89.6%) of 993 repeatedly reactive samples were also Multispot-reactive: 882 for HIV-1; three for only HIV-2; and five for both HIV-1 and HIV-2. All three HIV-2-only Multispot-positives along with a single dually reactive HIV-1/2 Multispot-positive were also HIV-2 immunoblot-positive; the latter was HIV-1 RNA negative and HIV-2 RNA positive. Conclusions The Multispot rapid test performed well as a supplemental test for HIV-1/2 diagnostic testing. Four new HIV-2 infections (0.45%) were identified from among 890 Multispot-reactive tests. The use of HIV-1 WB alone to confirm HIV-1/2 screening assays may underestimate the true prevalence of HIV-2 infection in the United States. PMID:24342468

Ramos, Eric M.; Harb, Socorro; Dragavon, Joan; Coombs, Robert W.

2014-01-01

129

POSSIBILITIES POSSIBILITIES  

E-print Network

of the importance of creating sustainable businesses that value ethical, social, and environmental responsibilities speakers have become an important part of the curriculum at the School of Business Administration. intErnshipBUSINESS ENDLESS POSSIBILITIES DEAN'S REPORT 2012 #12;2 3 BUSINESS ENDLESS POSSIBILITIES Welcome

Hayden, Nancy J.

130

HIV UPDATE: AGING & HIV  

E-print Network

HIV UPDATE: AGING & HIV SEPTEMBER 2012, Issue 9 Tlaleletso is a monthly publication produced-friendly format. This month's Taleletso provides an introduction to the topic of HIV and Aging. For a more is an invaluable resource for doctors managing HIV patients. Next month Tlaleletso will discuss the Management

Bushman, Frederic

131

HIV UPDATE: BOTSWANA HIV  

E-print Network

HIV UPDATE: BOTSWANA HIV CONFERENCE OCTOBER 2012, Issue 10 Tlaleletso is a monthly publication presentations from the Botswana HIV conference, which was held in Gaborone from September 19th to 22nd, 2012. Next month's Tlaleletso will discuss HIV and Cancer. If there are other topics you would like

Bushman, Frederic

132

Low-molecular-weight anti-HIV-1 peptides from the amino-terminal sequence of RANTES: possible lead compounds for coreceptor-directed anti-HIV-1 agents  

Microsoft Academic Search

A series of small peptides corresponding to the amino-terminal sequence of RANTES were synthesized, and their anti-HIV-1 activity was evaluated. Pentapeptides, H-(10Ala-RANTES 6-10)-OH and Ac-(10Ala-RANTES 6-10)-NH2, were the smallest anti-HIV-1 peptides so far developed, and would be potentially important lead compounds for coreceptor-directed anti-HIV-1 drugs.

Yasuhiro Nishiyama; Tsutomu Murakami; Keisuke Kurita; Naoki Yamamoto

1999-01-01

133

Emerging role of cancer stem cells in the biology and treatment of ovarian cancer: basic knowledge and therapeutic possibilities for an innovative approach  

PubMed Central

In 2013 there will be an estimated 22,240 new diagnoses and 14,030 deaths from ovarian cancer in the United States. Despite the improved surgical approach and the novel active drugs that are available today in clinical practice, about 80% of women presenting with late-stage disease have a 5-year survival rate of only 30%. In the last years a growing scientific knowledge about the molecular pathways involved in ovarian carcinogenesis has led to the discovery and evaluation of several novel molecular targeted agents, with the aim to test alternative models of treatment in order to overcome the clinical problem of resistance. Cancer stem cells tend to be more resistant to chemotherapeutic agents and radiation than more differentiated cellular subtypes from the same tissue. In this context the study of ovarian cancer stem cells is taking on an increasingly important strategic role, mostly for the potential therapeutic application in the next future. In our review, we focused our attention on the molecular characteristics of epithelial ovarian cancer stem cells, in particular on possible targets to hit with targeted therapies. PMID:23902592

2013-01-01

134

A Possible Novel Anti-Inflammatory Mechanism for the Pharmacological Prolyl Hydroxylase Inhibitor 3,4-Dihydroxybenzoate: Implications for Use as a Therapeutic for Parkinson's Disease  

PubMed Central

Parkinson's disease (PD) is an age-related neurodegenerative disorder characterized in part by the preferential loss of nigrostriatal dopaminergic neurons. Although the precise etiology of PD is unknown, accumulating evidence suggests that PD involves microglial activation that exerts neurotoxic effects through production of proinflammatory cytokines and increased oxidative and nitrosative stress. Thus, controlling microglial activation has been suggested as a therapeutic target for combating PD. Previously we demonstrated that pharmacological inhibition of a class of enzymes known as prolyl hydroxylases via 3,4-dihydroxybenzoate administration protected against MPTP-induced neurotoxicity, however the exact mechanisms involved were not elucidated. Here we show that this may be due to DHB's ability to inhibit microglial activation. DHB significantly attenuated LPS-mediated induction of nitric oxide synthase and pro-inflammatory cytokines in murine BV2 microglial cells in vitro in conjunction with reduced ROS production and activation of NF?B and MAPK pathways possibly due to up-regulation of HO-1 levels. HO-1 inhibition partially abrogates LPS-mediated NF?B activity and subsequent NO induction. In vivo, DHB pre-treatment suppresses microglial activation elicited by MPTP treatment. Our results suggest that DHB's neuroprotective properties could be due to its ability to dampen induction of microglial activation via induction of HO-1. PMID:22666629

Chinta, Shankar J.; Rajagopalan, Subramanian; Ganesan, Abirami; Andersen, Julie K.

2012-01-01

135

Proteomics identified overexpression of SET oncogene product and possible therapeutic utility of protein phosphatase 2A in alveolar soft part sarcoma.  

PubMed

Alveolar soft part sarcoma (ASPS) is an exceedingly rare sarcoma refractory to standard chemotherapy. Although several molecular targeting drugs have been applied for ASPS, their clinical significance has not yet been established, and novel therapeutic strategies have long been required. The aim of this study was to identify proteins aberrantly regulated in ASPS and to clarify their clinical significance. Protein expression profiling of tumor and nontumor tissues from 12 ASPS patients was performed by 2-D difference gel electrophoresis and mass spectrometry. We found that the expression of 145 proteins differed significantly. Among them, further investigation was focused on the SET protein, which has multifunctional roles in cancers. Immunohistochemistry confirmed overexpression of SET in all 15 ASPS cases examined. Gene silencing of SET significantly decreased cell proliferation, invasion, and migration against a background of induced apoptosis. SET is known to be an inhibitor of phosphatase 2A (PP2A), which functions as a tumor suppressor by inhibiting the signal transduction pathway and inducing apoptosis. We found that a PP2A activator, FTY720, decreased cell proliferation through apoptosis. Together, our findings may suggest the possible contribution of SET to the tumor progression and the utility of FTY720 for treatment of ASPS. PMID:24621013

Kubota, Daisuke; Yoshida, Akihiko; Kawai, Akira; Kondo, Tadashi

2014-05-01

136

Differential cellular FGF2 upregulation in the rat facial nucleus following axotomy, functional electrical stimulation and corticosterone: a possible therapeutic target to Bell's palsy  

Microsoft Academic Search

BACKGROUND: The etiology of Bell's palsy can vary but anterograde axonal degeneration may delay spontaneous functional recovery leading the necessity of therapeutic interventions. Corticotherapy and\\/or complementary rehabilitation interventions have been employed. Thus the natural history of the disease reports to a neurotrophic resistance of adult facial motoneurons leading a favorable evolution however the related molecular mechanisms that might be therapeutically

Karen F Coracini; Caio J Fernandes; Almir F Barbarini; César M Silva; Rodrigo T Scabello; Gabriela P Oliveira; Gerson Chadi

2010-01-01

137

Growth and Trophic Factors, pH and the Na+\\/H+ Exchanger in Alzheimer's Disease, Other Neurodegenerative Diseases and Cancer: New Therapeutic Possibilities and Potential Dangers  

Microsoft Academic Search

Abnormalities in the intricate intracellular signalling pathways play a key role in the deregulation of either spontaneous (normal or pathological) or induced (therapeutic) cell death mechanisms. Some of these pathways are in- creasingly becoming molecular therapeutic targets in different processes, ranging from neurodegenerative diseases to can- cer. Recent discoveries in research and treatment have shown that failure to induce selective

Salvador Harguindey; Stephan J. Reshkin; Gorka Orive; Jose Luis Arranz; Eduardo Anitua

2007-01-01

138

J Antimicrob Chemother . Author manuscript Virological and immunological response in HIV-1-infected patients with  

E-print Network

clinical routine conditions. MESH Keywords Adult ; Anti-HIV Agents ; pharmacokinetics ; therapeutic use ; Antiretroviral Therapy, Highly Active ; CD4 Lymphocyte Count ; Cohort Studies ; Drug Resistance, Viral ; Female ; HIV Infections ; drug therapy ; immunology ; virology ; HIV-1 ; classification ; genetics ; isolation

Paris-Sud XI, Université de

139

AIDS . Author manuscript Infant feeding, HIV transmission and mortality at 18 months: the need for  

E-print Network

to be the targets of improvement strategies. MESH Keywords AIDS Serodiagnosis ; methods ; Adolescent ; Adult ; Anti-HIV ; Developing Countries ; Female ; HIV Infections ; drug therapy ; mortality ; transmission ; HIV-1 ; Health ; Male ; Nevirapine ; therapeutic use ; Pregnancy ; Pregnancy Complications, Infectious ; drug therapy

Boyer, Edmond

140

HIV/AIDS Clinical Trials  

MedlinePLUS

... Therapeutic Vaccines Clinical Trial News Tuesday, February 24, 2015 CDC Statement on IPERGAY Trial of Pre-Exposure ... Who Have Sex with Men Wednesday, February 18, 2015 NIH-Sponsored HIV Vaccine Trial Launches in South ...

141

Prison Therapeutic Community Treatment for Female Offenders: Profiles and Preliminary Findings for Mental Health and Other Variables (Crime, Substance Use and HIV Risk)  

ERIC Educational Resources Information Center

This random assignment study compared women in a prison Therapeutic Community (TC) program with those in a cognitive-behavioral intervention. Over two thirds of study subjects received a lifetime diagnosis of severe mental disorder, nearly one-half received a diagnosis of PTSD, and virtually all reported exposure to trauma. Preliminary analysis (n…

Sacks, Joann Y.; Sacks, Stanley; Mckendrick, Karen; Banks, Steven; Schoeneberger, Marlies; Hamilton, Zachary; Stommel, Joseph; Shoemaker, Joanie

2008-01-01

142

Mother to child transmission of HIV in Vitória, Brazil: Factors associated with lack of HIV prevention  

Microsoft Academic Search

Screening HIV infection in pregnancy provides an ideal opportunity to make an early diagnosis in women in order to provide treatment to reduce vertical transmission to the newborn. The objectives were to describe the profile of HIV-infected pregnant women attending municipal hospitals in Vitória and to identify the causes associated with the lack of HIV therapeutic prophylaxis. Descriptive analysis of

A. E. Miranda; R. A. Soares; B. C. Prado; R. B. Monteiro; N. C. Figueiredo

2005-01-01

143

Nigella sativa concoction induced sustained seroreversion in HIV patient.  

PubMed

Nigella sativa had been documented to possess many therapeutic functions in medicine but the least expected is sero-reversion in HIV infection which is very rare despite extensive therapy with highly active anti-retroviral therapy (HAART). This case presentation is to highlight the complete recovery and sero-reversion of adult HIV patient after treatment with Nigella sativa concoction for the period of six months. The patient presented to the herbal therapist with history of chronic fever, diarrhoea, weight loss and multiple papular pruritic lesions of 3 months duration. Examination revealed moderate weight loss, and the laboratory tests of ELISA (Genscreen) and western blot (new blot 1 & 2) confirmed sero-positivity to HIV infection with pre-treatment viral (HIV-RNA) load and CD4 count of 27,000 copies/ml and CD4 count of 250 cells/ mm(3) respectively. The patient was commenced on Nigella sativa concoction 10 mls twice daily for 6 months.. He was contacted daily to monitor side-effects and drug efficacy. Fever, diarrhoea and multiple pruritic lesions disappeared on 5th, 7th and 20th day respectively on Nigella sativa therapy. The CD4 count decreased to 160 cells/ mm3 despite significant reduction in viral load (?1000 copies/ml) on 30th day on N. sativa. Repeated EIA and Western blot tests on 187th day on Nigella sativa therapy was sero-negative. The post therapy CD4 count was 650 cells/ mm(3) with undetectable viral (HIV-RNA) load. Several repeats of the HIV tests remained sero-negative, aviraemia and normal CD4 count since 24 months without herbal therapy. This case report reflects the fact that there are possible therapeutic agents in Nigella sativa that may effectively control HIV infection. PMID:24311845

Onifade, Abdulfatah Adekunle; Jewell, Andrew Paul; Adedeji, Waheed Adeola

2013-01-01

144

Potential Anti-HIV Agents from Marine Resources: An Overview  

PubMed Central

Human immunodeficiency virus (HIV) infection causes acquired immune deficiency syndrome (AIDS) and is a global public health issue. Anti-HIV therapy involving chemical drugs has improved the life quality of HIV/AIDS patients. However, emergence of HIV drug resistance, side effects and the necessity for long-term anti-HIV treatment are the main reasons for failure of anti-HIV therapy. Therefore, it is essential to isolate novel anti-HIV therapeutics from natural resources. Recently, a great deal of interest has been expressed regarding marine-derived anti-HIV agents such as phlorotannins, sulfated chitooligosaccharides, sulfated polysaccharides, lectins and bioactive peptides. This contribution presents an overview of anti-HIV therapeutics derived from marine resources and their potential application in HIV therapy. PMID:21339954

Vo, Thanh-Sang; Kim, Se-Kwon

2010-01-01

145

Quasispecies tropism and compartmentalization in gut and peripheral blood during early and chronic phases of HIV-1 infection: possible correlation with immune activation markers.  

PubMed

HIV quasispecies was analysed in plasma and proviral genomes hosted by duodenal mucosa and peripheral blood cells (PBMC) from patients with early or chronic infection, with respect to viral heterogeneity, tropism compartmentalization and extent of immune activation. Seventeen HIV-1-infected combined antiretroviral therapy naive patients were enrolled (11 early infection and six chronic infection). V3 and nef genomic regions were analysed by ultra-deep pyrosequencing. Sequences were used to infer co-receptor usage and to construct phylogenetic trees. As markers of immune activation, plasma sCD14 and soluble tumour necrosis factor receptor II (sTNFRII) levels were measured. Median diversity of HIV RNA was lower in patients with early infection versus chronic infection patients. Overall, direct correlation was observed between V3 diversity and X4 frequency; V3 diversity of HIV RNA was inversely correlated with CD4 T-cell count; median sCD14 and sTNFRII values were similar in early and chronic patients, but X4 frequency of HIV RNA was directly correlated with plasma sCD14. The proportion of patients harbouring X4 variants and median intra-patient X4 frequency of proviral genomes tended to be higher in chronic infection than early infection patients. More pronounced compartmentalization of proviral quasispecies in gut compared with PBMC samples was observed in patients with early infection compared with chronic patients. The loss of gut/PBMC compartmentalization in more advanced stages of HIV infection was confirmed by longitudinal observation. More studies are needed to understand the pathogenetic significance of early HIV quasispecies compartmentalization and progressive intermixing of viral variants in subsequent phases of the infection, as well as the role of immune activation in tropism switch. PMID:24134524

Rozera, G; Abbate, I; Vlassi, C; Giombini, E; Lionetti, R; Selleri, M; Zaccaro, P; Bartolini, B; Corpolongo, A; D'Offizi, G; Baiocchini, A; Del Nonno, F; Ippolito, G; Capobianchi, M R

2014-03-01

146

HIV Symptoms  

MedlinePLUS

... Submit Home > HIV/AIDS > What is HIV/AIDS? HIV/AIDS This information in Spanish ( en espańol ) HIV symptoms Photo courtesy of AIDS.gov Facing AIDS ... and brain Return to top More information on HIV symptoms Explore other publications and websites Basic Information ...

147

[Therapeutic endosonography].  

PubMed

Endoscopic ultrasonography (EUS)-guided interventions are an essential tool for complex (such as combined or subsequent) therapeutic measures and are, in current as well as future endoscopy, an indispensable part of modern gastroenterology. Longitudinal EUS scanners allow one to puncture transluminally both mediastinal and abdominal lesions which cannot be approached with other techniques. Using the EUS-guided puncture of such pathological lesions, it becomes possible to perform further, more advanced endoscopic interventions which thus become safer as well as more efficient and are associated with a lower complication rate compared with conventional endoscopic or even surgical interventions. A crucial aspect in interventional EUS is the adequate, less traumatic treatment of pancreatic pseudocysts. The transluminal route for interventions spanning from the approach to the placement of a drainage for abscesses and/or necroses is considerably easier under EUS-guidance, including better outcomes. Novel approaches and interventions are the internal EUS-guided insertion of a transluminal (from the upper GI tract) I) cholangiodrainage in patients with malignant obstruction of the bile duct but no option to achieve sufficient conventional cholangiodrainage with ERC or PTC, II) pancreaticodrainage in symptomatic patients with enlarged pancreatic duct -/+ pancreatic fistula postoperatively or in patients with chronic pancreatitis, which may be considered new therapeutic strategies with non-operative intentions and/or low invasiveness. PMID:18537083

Will, U

2008-06-01

148

Therapeutic amprenavir concentrations in cerebrospinal fluid.  

PubMed

Antiretrovirals that reach higher concentrations in cerebrospinal fluid (CSF) are associated with better control of HIV in CSF and possibly better neurocognitive performance. The objective of this study was to determine whether amprenavir (APV) concentrations in CSF are in the therapeutic range. Individuals were selected based on the use of regimens that included fosamprenavir (FPV), a prodrug of APV, and the availability of stored CSF and matched plasma. Total APV was measured in 119 matched CSF-plasma pairs from 75 subjects by high-performance liquid chromatography (HPLC) (plasma) or liquid chromatography tandem mass spectrometry (LC/MS/MS) (CSF). Concentrations were compared to the 50% inhibitory concentration (IC??) for wild-type HIV (5.6 ng/ml). Subjects were predominantly middle-aged (median 44 years) white (57%) men (78%) with AIDS (77%). APV was detected in all but 4 CSF specimens, with a median concentration of 24.8 ng/ml (interquartile range [IQR], 16.2 to 44.0). The median CSF-to-plasma ratio was 0.012 (IQR, 0.008 to 0.018). CSF concentrations correlated with plasma concentrations (rho = 0.61; P < 0.0001) and with postdose sampling interval (rho = -0.29; P = 0.0019). APV concentrations in CSF exceeded the median IC?? for wild-type HIV in more than 97% of CSF specimens with detectable APV by a median of 4.4-fold (IQR, 2.9 to 7.9). We conclude that administration of fosamprenavir should contribute to control of HIV replication in the central nervous system (CNS) as a component of effective antiretroviral regimens. PMID:22290964

Croteau, David; Letendre, Scott; Best, Brookie M; Rossi, Steven S; Ellis, Ronald J; Clifford, David B; Collier, Ann C; Gelman, Benjamin B; Marra, Christina M; McArthur, Justin; McCutchan, J Allen; Morgello, Susan; Simpson, David M; Way, Lauren; Capparelli, Edmund; Grant, Igor

2012-04-01

149

HIV / AIDS  

MedlinePLUS

... on. Read more information on enabling JavaScript. HIV/AIDS Skip Content Marketing Share this: Main Content Area ... are being affected by HIV/AIDS. Understanding HIV/AIDS Overview Cause Transmission Symptoms Testing and Diagnosis Treatment ...

150

Neurophysiological study on possible protective and therapeutic effects of Sidr (Zizyphus spina-christi L.) leaf extract in male albino rats treated with pentylenetetrazol  

PubMed Central

In this study, anti-convulsant effect of Sidr leaf extract was examined by using pentylenetetrazol (PTZ) model on male albino rat by evaluating the changes in norepinephrine (NE), dopamine (DA) and serotonin (5-HT) contents in different brain regions (cerebellum, brainstem, striatum, cerebral cortex, hypothalamus and hippocampus). The administration of subconvulsive dose of PTZ (40 mg/kg i.p.) every other day for 9 days caused a significant decrease in monoamine content in different brain areas, this is may be due to the increase in nitric oxide levels, although antagonized the GABAA receptors which led to neurotransmitter release so the content is decreased. Administration of PTZ after treatment with Sidr (50 mg/kg i.p.) leaf extract for 3 weeks as a protective group and administration of Sidr leaf extract for 3 weeks after treatment of PTZ as a therapeutic group caused significant increase in NE, DA, and 5-HT contents in all tested brain regions at most of the time intervals studied. This may be due to the presence of peptide and cyclopeptide alkaloids in the extract which inhibit neurotransmitter activity which led to the inhibition of neurotransmitter release. From these results, we can say that the Sidr leaf extract has neuroprotective and therapeutic roles against pentylenetetrazol convulsant effect. PMID:23961090

Waggas, Abeer M.; Al-Hasani, Reem H.

2010-01-01

151

G-quartets assembly within a G-rich DNA flap. A possible event at the center of the HIV-1 genome  

PubMed Central

Stretches of guanines can associate in vitro through Hoogsteen hydrogen bonding to form four-stranded structures. In the HIV-1 central DNA flap, generated by reverse transcriptase at the end of retrotranscription, both the two 99 nt-long overlapping (+) strands contain two adjacent tracts of guanines. This study demonstrates that oligonucleotides containing these G-clusters form highly stable G-quadruplexes of various structures in vitro, whose formation was controlled by an easy and reversible protocol using sodium hydroxide. Among these sequences, a G?2 hairpin dimer was the most stable structure adopted by the 5?-tail of the (+) downstream strand. Since the two (+) strands of the HIV-1 central DNA flap hold these G-clusters, and based on the properties of reverse branch migration in DNA flaps, constructions using HIV-1 sequences were assembled to mimic small DNA flaps where the G-clusters are neighbors. G-quartets were successfully probed in such flaps. They were induced by potassium and by a dibenzophenanthroline derivative already known to stabilize them. Such results suggest some function(s) for G-quartets associated with a DNA flap in the HIV-1 pre-integration steps, and argue for their transient formation during the processing of G-rich DNA flaps at the time of replication and/or repair. PMID:12466553

Lyonnais, Sébastien; Hounsou, Candide; Teulade-Fichou, Marie-Paule; Jeusset, Josette; Cam, Eric Le; Mirambeau, Gilles

2002-01-01

152

Are major reductions in new HIV infections possible with people who inject drugs? The case for low dead-space syringes in highly affected countries.  

PubMed

Circumstantial evidence from laboratory studies, mathematical models, ecological studies and bio behavioural surveys, suggests that injection-related HIV epidemics may be averted or reversed if people who inject drugs (PWID) switch from using high dead-space to using low dead-space syringes. In laboratory experiments that simulated the injection process and rinsing with water, low dead space syringes retained 1000 times less blood than high dead space syringes. In mathematical models, switching PWID from high dead space to low dead space syringes prevents or reverses injection-related HIV epidemics. No one knows if such an intervention is feasible or what effect it would have on HIV transmission among PWID. Feasibility studies and randomized controlled trials (RCTs) will be needed to answer these questions definitively, but these studies will be very expensive and take years to complete. Rather than waiting for them to be completed, we argue for an approach similar to that used with needle and syringe programs (NSP), which were promoted and implemented before being tested more rigorously. Before implementation, rapid assessments that involve PWID will need to be conducted to ensure buy-in from PWID and other local stakeholders. This commentary summarizes the existing evidence regarding the protective effects of low dead space syringes and estimates potential impacts on HIV transmission; it describes potential barriers to transitioning PWID from high dead space to low dead space needles and syringes; and it presents strategies for overcoming these barriers. PMID:22884539

Zule, William A; Cross, Harry E; Stover, John; Pretorius, Carel

2013-01-01

153

Cutaneous mucinoses and HIV infection.  

PubMed

In the last few years cutaneous mucinoses have been reported with increased frequency in HIV patients. We report the occurrence of scleredema, reticular erythematous mucinosis and lichen myxoedematosus in three different HIV-infected patients, review the literature and discuss the possible relationship between mucin deposits and HIV infection. This is the first report of scleredema and the second of reticular erythematous mucinosis in an HIV-infected patient. Only the association of HIV infection with lichen myxoedematosus seems to be more than coincidental. PMID:9990377

Rongioletti, F; Ghigliotti, G; De Marchi, R; Rebora, A

1998-12-01

154

Addressing Ebola-related Stigma: Lessons Learned from HIV/AIDS  

PubMed Central

Background HIV/AIDS and Ebola Virus Disease (EVD) are contemporary epidemics associated with significant social stigma in which communities affected suffer from social rejection, violence, and diminished quality of life. Objective To compare and contrast stigma related to HIV/AIDS and EVD, and strategically think how lessons learned from HIV stigma can be applied to the current EVD epidemic. Methods To identify relevant articles about HIV/AIDS and EVD-related stigma, we conducted an extensive literature review using multiple search engines. PubMed was used to search for relevant peer-reviewed journal articles and Google for online sources. We also consulted the websites of the World Health Organization (WHO), Centers for Disease Control and Prevention (CDC), and the National Institutes of Health to retrieve up-to-date information about EVD and HIV/AIDS. Results Many stigmatizing attitudes and behaviors directed towards those with EVD are strikingly similar to those with HIV/AIDS but there are significant differences worthy of discussion. Both diseases are life-threatening and there is no medical cure. Additionally misinformation about affected groups and modes of transmission runs rampant. Unlike in persons with EVD, historically criminalized and marginalized populations carry a disproportionately higher risk for HIV infection. Moreover, mortality due to EVD occurs within a shorter time span as compared to HIV/AIDS. Conclusions Stigma disrupts quality of life, whether it is associated with HIV infection or EVD. When addressing EVD, we must think beyond the immediate clinical therapeutic response, to possible HIV implications of serum treatment. There are emerging social concerns of stigma associated with EVD infection and double stigma associated with EVD and HIV infection. Drawing upon lessons learned from HIV, we must work to empower and mobilize prominent members of the community, those who recovered from the disease, and organizations working at the grassroots level to disseminate clear and accurate information about EVD transmission and prevention while promoting stigma reduction in the process. In the long run, education, prevention, and a therapeutic vaccine will be the optimal solutions for reducing the stigma associated with both EVD and HIV. PMID:25382685

Davtyan, Mariam; Brown, Brandon; Folayan, Morenike Oluwatoyin

2014-01-01

155

Universal Tre (uTre) recombinase specifically targets the majority of HIV-1 isolates  

PubMed Central

Current drugs against HIV can suppress the progression to AIDS but cannot clear the patient from the virus. Because of potential side effects of these drugs and the possible development of drug resistance, finding a cure for HIV infection remains a high priority of HIV/AIDS research. We recently generated a recombinase (termed Tre) tailored to efficiently eradicate the provirus from the host genome of HIV-1 infected cells by specifically targeting a sequence that is present in the long terminal repeats (LTRs) of the viral DNA [1]. In vivo analyses in HIV-infected humanized mice demonstrated highly significant antiviral effects of Tre recombinase [2]. However, the fact that Tre recognizes a particular HIV-1 subtype A strain may limit its broad therapeutic application. To advance our Tre-based strategy towards a universally efficient cure, we have engineered a new, universal recombinase (uTre) applicable to the majority of HIV-1 infections by the various virus strains and subtypes. We employed the search tool SeLOX [3] in order to find a well-conserved HIV-1 proviral sequence that could serve as target site for a universal Tre from sequences compiled in the Los Alamos HIV Sequence Database. We selected a candidate (termed loxLTRu) with a mean conservation rate of 94% throughout the major HIV-1 subtype groups A, B and C. We applied loxLTRu as substrate in our established substrate-linked protein evolution (SLiPE) process [4] and evolved the uTre recombinase in 142 evolution cycles. Highly specific enzymatic activity on loxLTRu is demonstrated for uTre in both Escherichia coli and human cells. Naturally occurring viral variants with single mutations within the loxLTRu sequence are also shown to be efficiently targeted by uTre, further increasing the range of applicability of the recombinase. Potential off-target sites in the human genome are not recombined by uTre. Furthermore, uTre expression in primary human T cells shows no obvious Tre-related cytopathic or genotoxic effects. Finally, uTre expressing mice show no undesired phenotypes during their normal lifespan. We have developed a broad-range HIV-1 LTR specific recombinase that has the potential to be effective against the vast majority of HIV-1 strains and to cure HIV-1 infected cells from the infection. These results strongly encouraged us in our confidence that a Tre recombinase-mediated HIV eradication strategy may become a valuable component of a future therapy for HIV-infected patients. PMID:25397454

Karpinski, Janet; Chemnitz, Jan; Hauber, Ilona; Abi-Ghanem, Josephine; Paszkowski-Rogacz, Maciej; Surendranath, Vineeth; Chakrabort, Debojyoti; Hackmann, Karl; Schröck, Evelin; Teresa Pisabarro, María; Hauber, Joachim; Buchholz, Frank

2014-01-01

156

Negative correlation between therapeutic success in radioiodine therapy and TcTUs: are TcTUs-adapted dose concepts the only possible answer?  

PubMed

Calculation of iodine-131 activities for radioiodine treatment (RIT) in patients with disseminated thyroid autonomy may be difficult because of uncertainties in the determination of the autonomous volume (vol(aut)). The algorithm established by Emrich is used for calculation of the vol(aut) based on the TcTUs (technetium thyroid uptake under TSH suppression) (vol(aut)= 5xTcTUs+0.6). Clinical experience using this approach has shown that there is a negative correlation between increasing TcTUs and the results of RIT. Our aim was to identify the reasons for this observation as well as to assess the relation between TcTUs and sonographic vol(aut). Furthermore, we intended to find an alternative algorithm for the TcTUs-based calculation of the vol(aut). Data from 100 patients with unifocal autonomy who met strict inclusion criteria were used to evaluate the correlation between TcTUs and sonographic vol(aut). Using Marinelli's algorithm, we calculated the therapeutic activities for a standardised patient at a target dose of 300 Gy. The vol(aut) was determined based on the TcTUs using the four published algorithms [Emrich 1993 (vol(aut)= 5xTcTUs+0.6), Kreisig 1992 (vol(aut)=10xTcTUs-9.3), Joseph 1977 (vol(aut)=8.33xTcTUs-6.67) and 1994 (vol(aut)=2.88xTcTUs+0.09)]. We then compared the results of the calculation of therapeutic activities obtained using Emrich's algorithm (with known success rates) with those obtained by the other algorithms in order to determine which algorithm would lead to better results in RIT. Only a weak correlation was found between the TcTUs and the sonographic vol(aut) ( r(2)=0.39). The calculated therapeutic activities of (131)I were similar for all algorithms at a TcTUs of around 2% but Joseph's (1977) and Kreisig's (1992) algorithms resulted in clearly higher activities than Emrich's algorithm at a TcTUs above 2%. The need for target doses to increase with TcTUs in RIT may be overcome by the use of adequate algorithms for determination of the vol(aut). The algorithm published by Joseph and co-workers in 1977 probably offers the most reliable approach to the TcTUs-based calculation of vol(aut) in RIT. In contrast to the other algorithms, it is based on autoradiographic planimetric data. Thus, it takes into account the polyclonal origin of thyroid nodules as well as the presence of regressive or cystic changes. The well-established algorithm of Emrich underestimates the true vol(aut), which explains the decreasing success of RIT with increasing TcTUs. PMID:12827311

Gotthardt, Martin; Nowack, Miriam; Béhé, Martin P; Schipper, Meike L; Schlieck, Anja; Höffken, Helmut; Behr, Thomas M

2003-08-01

157

Court disallows class action in hemophiliacs' HIV lawsuit.  

PubMed

Thousands of hemophiliacs who contracted HIV through blood-clotting products cannot sue the manufacturers in a class-action lawsuit, according to the Seventh U.S. Circuit Court of Appeals. The four drug companies involved in the suit would face intensive pressure to settle to avoid possible bankruptcy, according to the court. The plaintiffs argue that drug manufacturers could have protected hemophiliacs from HIV infection prior to the discovery of the first AIDS case in the United States in 1981. Since hepatitis B was transmitted through blood transfusions or blood-clotting products, the manufacturers could have either treated the blood or screened donors, thus protecting hemophiliacs from both hepatitis B and HIV. The plaintiffs also contend that the drug manufacturers dragged their heels about instituting precautions once researchers in the early 1980s began to suspect that HIV was transmitted through blood. The defendants named were Rhone-Poulenc Rorer of Collegeville, PA; Miles Inc. of Pittsburgh; Baxter Healthcare Corp. of Deerfield, IL; and Alpha Therapeutic Corp. of Los Angeles. The National Hemophilia Foundation was also named as a defendant charged with negligence and breach of fiduciary duty since it downplayed the risk of HIV transmission through blood products in the early 1980s. The plaintiffs reportedly have asked the Circuit Court of Appeals to reconsider the panel's ruling. If the decision stands, the plaintiffs would have to have their cases tried individually. PMID:11362391

1995-04-21

158

Hepatocellular carcinoma in HIV positive patients.  

PubMed

Highly active antiretroviral therapy (HAART) has dramatically changed the natural history of HIV-1-infected patients leading to increased survival and a better quality of life. Hepatitis C virus (HCV) and hepatitis B virus (HBV) infections are common among HIV-1-infected subjects and represent the most important risk factors for hepatocellular carcinoma (HCC). Whether HIV plays a direct role in hepatocellular carcinoma (HCC) pathogenesis remains to be established.HCC clinical course depends on stage of cancer disease, performance status and comorbidities. Therapeutic options include liver transplantation, local antiblastic chemotherapy and biological drugs. In the HIV setting few data are available about treatment options. The increased longevity of patients with HIV imposes new strategies for prevention and therapeutic management of patients. The aim of this article is to provide an up-to-date review of HIV-related HCC in the HAART era. PMID:23047511

Nunnari, G; Berretta, M; Pinzone, M R; Di Rosa, M; Berretta, S; Cunsolo, G; Malaguarnera, M; Cosentino, S; De Paoli, P; Schnell, J M; Cacopardo, B

2012-09-01

159

Bone alterations associated with HIV.  

PubMed

HIV infection and initiation of antiretroviral therapy (ART) have been consistently associated with decreased bone mineral density (BMD), with growing evidence linking HIV to an increased risk of fracture. This is especially concerning with the expanding number of older persons living with HIV. Interestingly, recent data suggest that HIV-infected children and youth fail to achieve peak BMD, possibly increasing their lifetime risk of fracture. Elucidating the causes of the bone changes in HIV-positive persons is challenging because of the multifactorial nature of bone disease in HIV, including contribution of the virus, immunosuppression, ART toxicity, and traditional osteoporosis risk factors, such as age, lower weight, tobacco, and alcohol use. Thus, practitioners must recognize the risk of low BMD and fractures and appropriately screen patients for osteoporosis if risk factors exist. If fractures do occur or elevated fracture risk is detected through screening, treatment with bisphosphonate medications appears safe and effective in the HIV+population. PMID:25064454

Warriner, Amy H; Mugavero, Michael; Overton, E Turner

2014-09-01

160

BET bromodomain-targeting compounds reactivate HIV from latency via a Tat-independent mechanism  

PubMed Central

The therapeutic potential of pharmacologic inhibition of bromodomain and extraterminal (BET) proteins has recently emerged in hematological malignancies and chronic inflammation. We find that BET inhibitor compounds (JQ1, I-Bet, I-Bet151 and MS417) reactivate HIV from latency. This is evident in polyclonal Jurkat cell populations containing latent infectious HIV, as well as in a primary T-cell model of HIV latency. Importantly, we show that this activation is dependent on the positive transcription elongation factor p-TEFb but independent from the viral Tat protein, arguing against the possibility that removal of the BET protein BRD4, which functions as a cellular competitor for Tat, serves as a primary mechanism for BET inhibitor action. Instead, we find that the related BET protein, BRD2, enforces HIV latency in the absence of Tat, pointing to a new target for BET inhibitor treatment in HIV infection. In shRNA-mediated knockdown experiments, knockdown of BRD2 activates HIV transcription to the same extent as JQ1 treatment, while a lesser effect is observed with BRD4. In single-cell time-lapse fluorescence microscopy, quantitative analyses across ~2,000 viral integration sites confirm the Tat-independent effect of JQ1 and point to positive effects of JQ1 on transcription elongation, while delaying re-initiation of the polymerase complex at the viral promoter. Collectively, our results identify BRD2 as a new Tat-independent suppressor of HIV transcription in latently infected cells and underscore the therapeutic potential of BET inhibitors in the reversal of HIV latency. PMID:23255218

Boehm, Daniela; Calvanese, Vincenzo; Dar, Roy D.; Xing, Sifei; Schroeder, Sebastian; Martins, Laura; Aull, Katherine; Li, Pao-Chen; Planelles, Vicente; Bradner, James E.; Zhou, Ming-Ming; Siliciano, Robert F.; Weinberger, Leor; Verdin, Eric; Ott, Melanie

2013-01-01

161

Plasmids encoding therapeutic agents  

DOEpatents

Plasmids encoding anti-HIV and anti-anthrax therapeutic agents are disclosed. Plasmid pWKK-500 encodes a fusion protein containing DP178 as a targeting moiety, the ricin A chain, an HIV protease cleavable linker, and a truncated ricin B chain. N-terminal extensions of the fusion protein include the maltose binding protein and a Factor Xa protease site. C-terminal extensions include a hydrophobic linker, an L domain motif peptide, a KDEL ER retention signal, another Factor Xa protease site, an out-of-frame buforin II coding sequence, the lacZ.alpha. peptide, and a polyhistidine tag. More than twenty derivatives of plasmid pWKK-500 are described. Plasmids pWKK-700 and pWKK-800 are similar to pWKK-500 wherein the DP178-encoding sequence is substituted by RANTES- and SDF-1-encoding sequences, respectively. Plasmid pWKK-900 is similar to pWKK-500 wherein the HIV protease cleavable linker is substituted by a lethal factor (LF) peptide-cleavable linker.

Keener, William K. (Idaho Falls, ID)

2007-08-07

162

HIV Viral Load  

MedlinePLUS

... that an HIV viral load test detects HIV RNA. What is an HIV DNA test? The HIV ... HIV-1-Infected Adults and Adolescents, Plasma HIV RNA Testing. AIDSinfo On-line information]. Available online through ...

163

HIV and Atherosclerosis  

MedlinePLUS

HIV and Atherosclerosis Updated:Jan 22,2014 Featured Video How is HIV Related to Atherosclerosis? Length: 2: ... improve your cholesterol ratios, with or without HIV. HIV and Your Heart • Home • About HIVHIV and ...

164

Treatment for HIV  

MedlinePLUS

... and Public Home » Treatment » Treatment Decisions and HIV HIV/AIDS HIV/AIDS HIV/AIDS Home For Veterans ... here Enter ZIP code here Treatment Decisions and HIV for Veterans and the Public Treatment for HIV: ...

165

HIV Testing Frequency  

MedlinePLUS

... Testing : HIV Testing Frequency Translate Text Size Print HIV Testing Frequency Testing Frequency How often should you ... local health department for proper care and information. HIV Testing HIV Test Locations HIV Test Types HIV ...

166

Therapeutic options for Middle East respiratory syndrome coronavirus (MERS-CoV)--possible lessons from a systematic review of SARS-CoV therapy.  

PubMed

The Middle East Respiratory Syndrome coronavirus (MERS-CoV) has been detected in a number of countries in the Middle East and Europe with an apparently high mortality rate. It is phylogenetically related to the SARS coronavirus and has also been associated with severe respiratory illness as well as nosocomial transmission in healthcare settings. Current international recommendations do not support any specific therapies; however, there are a number of agents, which were used during the SARS epidemic of 2003. It is possible that these might be active against the related MERS coronavirus. We have reviewed the literature on the safety and efficacy of therapies used in patients with SARS with a view to their potential use in patients with MERS-CoV infections. PMID:23993766

Momattin, Hisham; Mohammed, Khurram; Zumla, Alimuddin; Memish, Ziad A; Al-Tawfiq, Jaffar A

2013-10-01

167

Marijuana as therapy for people living with HIV\\/AIDS: Social and health aspects  

Microsoft Academic Search

Therapeutic use of marijuana has emerged as an important issue for people living with cancer, HIV\\/AIDS and multiple sclerosis. This paper examines therapeutic use of marijuana in the Positive Health cohort study, a longitudinal cohort study of men and women living with HIV\\/AIDS in NSW and Victoria, Australia. Factors that distinguish therapeutic use of marijuana from recreational use were assessed

A. Fogarty; P. Rawstorne; G. Prestage; J. Crawford; J. Grierson; S. Kippax

2007-01-01

168

HIV UPDATE: cancer & HIV  

E-print Network

management of cancer and HIV treatment can be complex, with important drug-drug interactions and overlapping 40% of all cancers in men1 . Pathogenesis KS is a spindle-cell tumor thought to derive from endothelial cell lineage. This condition carries a variable clinical course ranging from minimal mucocutaneous

Bushman, Frederic

169

HIV Transmission  

MedlinePLUS

... kissing Toilet seats. Can I get HIV from anal sex? Yes. In fact, having anal sex is the riskiest type of sex for ... may allow HIV to enter the body during anal sex, but the top is also at risk ...

170

HIV Prevention  

MedlinePLUS

... post-exposure prophylaxis. How can I prevent getting HIV from anal or vaginal sex? Choose less risky ... consistently and correctly. How can I prevent getting HIV from oral sex? Avoid having your partner ejaculate ...

171

HIV virus  

NSDL National Science Digital Library

HIV is a virus that can be transmitted through fluids exchanged in sexual activity. HIV eventually causes AIDS. AIDS patients have compromised immune systems and they eventually die from diseases that healthy humans would normally fight off very easily.

Carl Henderson (National Institutes of Health; )

2005-12-09

172

HIV/AIDS and Pregnancy  

MedlinePLUS

If you have HIV/AIDS and find out you are pregnant or think you may be pregnant, you should let your health care provider know as soon as possible. Some HIV/AIDS medicines may harm your baby. Your health ...

173

Association Between HIV-1 Coreceptor Usage and Resistance to Broadly Neutralizing Antibodies  

PubMed Central

Background: Recently discovered broadly neutralizing antibodies have revitalized hopes of developing a universal vaccine against HIV-1. Mainly responsible for new infections are variants only using CCR5 for cell entry, whereas CXCR4-using variants can become dominant in later infection stages. Methods: We performed a statistical analysis on two different previously published data sets. The first data set was a panel of 199 diverse HIV-1 isolates for which IC50 neutralization titers were determined for the broadly neutralizing antibodies VRC01, VRC-PG04, PG9, and PG16. The second data set contained env sequences of viral variants extracted from HIV-1–infected humanized mice treated with the antibody PGT128 and from untreated control mice. Results: For the panel of 199 diverse HIV-1 isolates, we found a statistically significant association between viral resistance to PG9 and PG16 and CXCR4 coreceptor usage (P = 0.0011 and P = 0.0010, respectively). Our analysis of viral variants from HIV-1–infected humanized mice under treatment with the broadly neutralizing antibody PGT128 indicated that certain antibodies might drive a viral population toward developing CXCR4 coreceptor usage capability (P = 0.0011 for the comparison between PGT128 and control measurement). Conclusions: These analyses highlight the importance of accounting for a possible coreceptor usage bias pertaining to the effectiveness of an HIV vaccine and to passive antibody transfer as therapeutic approach. PMID:25072615

Walter, Hauke; Lengauer, Thomas

2014-01-01

174

Eliminating the latent HIV reservoir by reactivation strategies  

PubMed Central

Combination antiretroviral therapy (cART) has transformed HIV from a deadly to a chronic disease, but HIV patients are still burdened with excess morbidity and mortality, long-term toxicities from cART, stigmatization, and insufficient access to cART worldwide. Thus, a cure for HIV would have enormous impact on society as well as the individual. As the complexity and mechanisms of HIV persistence during therapy are being unraveled, new therapeutic targets for HIV eradication are discovered. Substances that activate HIV production in the latently infected cells have recently received much attention. By turning on expression of latent HIV proviruses, reactivation strategies could contribute to the eradication HIV infection. Compounds that are currently being or soon to be tested in clinical trials are emphasized. The results from these trials will provide important clues as to whether or not reactivating strategies could become significant components of a cure for HIV. PMID:23563519

Rasmussen, Thomas A.; Tolstrup, Martin; Winckelmann, Anni; Řstergaard, Lars; Sřgaard, Ole S.

2013-01-01

175

Authentic HIV-1 integrase inhibitors  

PubMed Central

HIV-1 integrase (IN) is indispensable for HIV-1 replication and has become a validated target for developing anti-AIDS agents. In two decades of development of IN inhibition-based anti-HIV therapeutics, a significant number of compounds were identified as IN inhibitors, but only some of them showed antiviral activity. This article reviews a number of patented HIV-1 IN inhibitors, especially those that possess high selectivity for the strand transfer reaction. These compounds generally have a polar coplanar moiety, which is assumed to chelate two magnesium ions in the binding site. Resistance to those compounds, when given to patients, can develop as a result of IN mutations. We refer to those compounds as authentic IN inhibitors. Continued drug development has so far delivered one authentic IN inhibitor to the market (raltegravir in 2007). Current and future attention will be focused on the development of novel authentic IN inhibitors with the goal of overcoming viral resistance. PMID:21426159

Liao, Chenzhong; Marchand, Christophe; Burke, Terrence R; Pommier, Yves; Nicklaus, Marc C

2010-01-01

176

Melatonin in Chagas' disease. Possible therapeutic value.  

PubMed

Chagas' disease is a severe health problem in Latin America, causing approximately 50 000 deaths a year, with approximately 18 million infected people. About 25-30% of the patients infected with Trypanosoma cruzi develop the chronic form of the disease. The protective response against T. cruzi depends on both innate and acquired immunity involving macrophages, natural killer cells, T and B lymphocytes, and the production of proinflammatory Th-1 cytokines. In addition, an increased nitric oxide (NO) production in macrophages leading to effective microbicidal action is needed to control parasitemia. Melatonin is detectable in T. cruzi and may play a role in promoting infection whereas, when administered in high doses during the acute phase of T. cruzi infection, it can decrease parasitemia while reducing NO production. During chronic disease progression, the sustained oxidative stress concomitant to myocardial damage could be reduced by administering melatonin. It is hypothesized that the coordinated administration of a melatonin agonist like the MT1 /MT2 agonist ramelteon, that lacks antioxidant activity and may not affect NO production during the acute phase, and of melatonin in doses high enough to decrease oxidative damage, to preserve mitochondrial and to prevent cardiomyopathy during the chronic phase, could be a novel add-on treatment of Chagas' disease. PMID:22057179

Cardinali, Daniel P; Alvarez, Carlos B

2011-01-01

177

HIV Wellness Numbers  

MedlinePLUS Videos and Cool Tools

HIV Wellness Numbers Updated:Mar 22,2012 Featured Video The Basics of HIV Management Length: 2:37 ... Learn more about your important heart-health numbers . HIV and Your Heart • Home • About HIVHIV and ...

178

Human Microbiome and HIV/AIDS  

PubMed Central

Understanding of the human microbiome continues to grow rapidly; however, reports on changes in the microbiome after HIV infection are still limited. This review surveys the progress made in methodology associated with microbiome studies and highlights the remaining challenges to this field. Studies have shown that commensal oral, gut, vaginal, and penile bacteria are vital to the health of the human immune system. Our studies on crosstalk among oral and gastrointestinal soluble innate factors, HIV, and microbes indicated that the oral and gut microbiome was altered in the HIV-positive samples compared to the negative controls. The importance of understanding the bacterial component of HIV/AIDS, and likelihood of “crosstalk” between viral and bacterial pathogens, will help in understanding the role of the microbiome in HIV-infected individuals and facilitate identification of novel antiretroviral factors for use as novel diagnostics, microbicides, or therapeutics against HIV infection. PMID:22193889

Li, Yihong; Yang, Liying; Pei, Zhiheng; Poles, Michael; Abrams, William R.; Malamud, Daniel

2013-01-01

179

HIV Medicine: A Medical Texbook  

NSDL National Science Digital Library

HIV Medicine is an online medical textbook that provides comprehensive and timely information on HIV treatment. Chapters include background information on Acute HIV-1 Infection, and a detailed guide to HIV Therapy. There is also current information about side effects, Lipodystrophy Syndrome, and resistance testing. The online textbook includes an impressive, in-depth index of HIV drugs. Editors Christian Hoffmann and Bernd Sebastian Kamps have years of experience in the medical field and provide free and anonymous access of their text to the public. Collaborators include Nyasha Bakare, MD who has worked at the Research Institute for Genetic and Human Therapy (RIGHT) since 2001, and has been working on the clinical development of a therapeutic HIV vaccine. This Web site is easy to navigate and its layout nicely mirrors the organization of a paper textbook. It will be useful as a research tool for college and graduate students as well as for the layperson who desires more in-depth information on HIV and treatments. Join the mailing list to be notified of new chapters and updates. [TJS

Hoffmann, Christian

180

Therapeutic ultrasound  

Microsoft Academic Search

The use of ultrasound in medicine is now quite commonplace, especially with the recent introduction of small, portable and relatively inexpensive, hand-held diagnostic imaging devices. Moreover, ultrasound has expanded beyond the imaging realm, with methods and applications extending to novel therapeutic and surgical uses. These applications broadly include: tissue ablation, acoustocautery, lipoplasty, site-specific and ultrasound mediated drug activity, extracorporeal lithotripsy,

Lawrence A Crum

2004-01-01

181

Therapeutic Nanodevices  

NASA Astrophysics Data System (ADS)

Therapeutic nanotechnology offers minimally invasive therapies with high densities of function concentrated in small volumes, features that may reduce patient morbidity and mortality. Unlike other areas of nanotechnology, novel physical properties associated with nanoscale dimensionality are not the raison d'ętre of therapeutic nanotechnology, whereas the aggregation of multiple biochemical (or comparably precise) functions into controlled nanoarchitectures is. Multifunctionality is a hallmark of emerging nanotherapeutic devices, and multifunctionality can allow nanotherapeutic devices to perform multistep work processes, with each functional component contributing to one or more nanodevice subroutine such that, in aggregate, subroutines sum to a cogent work process. Cannonical nanotherapeutic subroutines include tethering (targeting) to sites of disease, dispensing measured doses of drug (or bioactive compound), detection of residual disease after therapy and communication with an external clinician/operator. Emerging nanotherapeutics thus blur the boundaries between medical devices and traditional pharmaceuticals. Assembly of therapeutic nanodevices generally exploits either (bio)material self-assembly properties or chemoselective bioconjugation techniques, or both. Given the complexity, composition, and the necessity for their tight chemical and structural definition inherent in the nature of nanotherapeutics, their cost of goods (COGs) might exceed that of (already expensive) biologics. Early therapeutic nanodevices will likely be applied to disease states which exhibit significant unmet patient need (cancer and cardiovascular disease), while application to other disease states well-served by conventional therapy may await perfection of nanotherapeutic design and assembly protocols.

Lee, Stephen; Ruegsegger, Mark; Barnes, Philip; Smith, Bryan; Ferrari, Mauro

182

Therapeutic Nanodevices  

NASA Astrophysics Data System (ADS)

Therapeutic nanotechnology offers minimally invasive therapies with high densities of function concentrated in small volumes, features that may reduce patient morbidity and mortality. Unlike other areas of nanotechnology, novel physical properties associated with nanoscale dimensionality are not the raison d'etre of therapeutic nanotechnology, whereas the aggregation of multiple biochemical (or comparably precise) functions into controlled nanoarchitectures is. Multifunctionality is a hallmark of emerging nanotherapeutic devices, and multifunctionality can allow nanotherapeutic devices to perform multi-step work processes, with each functional component contributing to one or more nanodevice subroutine such that, in aggregate, subroutines sum to a cogent work process. Cannonical nanotherapeutic subroutines include tethering (targeting) to sites of disease, dispensing measured doses of drug (or bioactive compound), detection of residual disease after therapy and communication with an external clinician/operator. Emerging nanotherapeutics thus blur the boundaries between medical devices and traditional pharmaceuticals. Assembly of therapeutic nanodevices generally exploits either (bio)material self assembly properties or chemoselective bioconjugation techniques, or both. Given the complexity, composition, and the necessity for their tight chemical and structural definition inherent in the nature of nanotherapeutics, their cost of goods (COGs) might exceed that of (already expensive) biologics. Early therapeutic nanodevices will likely be applied to disease states which exhibit significant unmet patient need (cancer and cardiovascular disease), while application to other disease states well-served by conventional therapy may await perfection of nanotherapeutic design and assembly protocols.

Lee, Stephen C.; Ruegsegger, Mark; Barnes, Philip D.; Smith, Bryan R.; Ferrari, Mauro

183

Dendritic cell based vaccines for HIV infection  

PubMed Central

Dendritic cells have a central role in HIV infection. On one hand, they are essential to induce strong HIV-specific CD4+ helper T-cell responses that are crucial to achieve a sustained and effective HIV-specific CD8+ cytotoxic T-lymphocyte able to control HIV replication. On the other hand, DCs contribute to virus dissemination and HIV itself could avoid a correct antigen presentation. As the efficacy of immune therapy and therapeutic vaccines against HIV infection has been modest in the best of cases, it has been hypothesized that ex vivo generated DC therapeutic vaccines aimed to induce effective specific HIV immune responses might overcome some of these problems. In fact, DC-based vaccine clinical trials have yielded the best results in this field. However, despite these encouraging results, functional cure has not been reached with this strategy in any patient. In this Commentary, we discuss new approaches to improve the efficacy and feasibility of this type of therapeutic vaccine. PMID:23912672

García, Felipe; Plana, Montserrat; Climent, Nuria; León, Agathe; Gatell, Jose M; Gallart, Teresa

2013-01-01

184

HIV Medicine  

NSDL National Science Digital Library

From Flying Publisher, _HIV Medicine 2005_ is a free, online "medical textbook that provides a comprehensive and up-to-date overview of the treatment of HIV Infection." This edition is an update of the 2003 version of the textbook (reported on in the June 13, 2003 NSDL Scout Report for Life Sciences). Chapter titles in the textbook include HIV Testing, HIV and Pulmonary Diseases, Mitochondrial Toxicity, HIV and HBV Coinfections, and Traveling with HIV, to name a few. The textbook is available in both German and English. Please note that while certain sections of the 2005 edition are currently available, many sections are still in the process of being published on the site. Sections from the 2003 edition are standing in for some of the forthcoming 2005 sections. The entire 352-page 2003 edition is available for download at this site as well.

185

Mechanisms of inhibition of HIV replication by non-nucleoside reverse transcriptase inhibitors.  

PubMed

The non-nucleoside reverse transcriptase (RT) inhibitors (NNRTIs) are a therapeutic class of compounds that are routinely used, in combination with other antiretroviral drugs, to treat HIV-1 infection. NNRTIs primarily block HIV-1 replication by preventing RT from completing reverse transcription of the viral single-stranded RNA genome into DNA. However, some NNRTIs, such as efavirenz, have been shown to inhibit the late stages of HIV-1 replication by interfering with HIV-1 Gag-Pol polyprotein processing, while others, such as the pyrimidinediones, have been shown to inhibit both HIV-1 RT-mediated reverse transcription and HIV-1/HIV-2 viral entry. Accordingly, in this review we describe the multiple mechanisms by which NNRTIs inhibit HIV-1 reverse transcription (and in some cases HIV-2 reverse transcription) and other key steps involved in HIV-1/HIV-2 replication. PMID:18372072

Sluis-Cremer, Nicolas; Tachedjian, Gilda

2008-06-01

186

Women and HIV  

MedlinePLUS

... is called HIV positive (HIV+). HIV makes it hard for your body to fight off sickness. How do you get HIV? HIV is spread through body fluids like blood, semen, or breast milk. You can get HIV when you : Have sex with a person who is HIV+ and do ...

187

Conserved stem-loop structures in the HIV1 RNA region containing the A3 3' splice site and its cis-regulatory element: possible involvement in RNA splicing  

Microsoft Academic Search

The HIV-1 transcript is alternatively spliced to over 30 different mRNAs .W hether RNA secondary structure can influence HIV-1 RNA alternative splicing has not previousl yb een examined. Here we have determined the secondary structure of the HIV-1\\/BRU RNA segment, containing the alternative A3, A4a, A4b, A4 ca nd A5 3' splice sites .S ite A3, required for tat mRNA

Sandrine Jacquenet; S. Bilodeau; L aurence Damier; Annie Mougin; C. M artin Stoltzfus; Christiane Branlant

2001-01-01

188

Therapeutic mammaplasty.  

PubMed

Therapeutic mammaplasty is a term for the oncoplastic application of breast reduction and mastopexy techniques to treat selected breast tumours by breast conserving surgery (BCS). It has the potential to increase the indications for BCS as well as achieve more acceptable aesthetic results from it in suitable women. Now an established technique in the range of oncoplastic options for women with breast cancer, it finds common application and is associated with good oncological and quality of life outcomes. PMID:24889526

Macmillan, R D; James, R; Gale, K L; McCulley, S J

2014-07-01

189

HIV-1 Tat-based vaccines: an overview and perspectives in the field of HIV/AIDS vaccine development.  

PubMed

The HIV epidemic continues to represent one of the major problems worldwide, particularly in the Asia and Sub-Saharan regions of the world, with social and economical devastating effects. Although antiretroviral drugs have had a dramatically beneficial impact on HIV-infected individuals that have access to treatment, it has had a negligible impact on the global epidemic. Hence, the inexorable spreading of the HIV pandemic and the increasing deaths from AIDS, especially in developing countries, underscore the urgency for an effective vaccine against HIV/AIDS. However, the generation of such a vaccine has turned out to be extremely challenging. Here we provide an overview on the rationale for the use of non-structural HIV proteins, such as the Tat protein, alone or in combination with other HIV early and late structural HIV antigens, as novel, promising preventative and therapeutic HIV/AIDS vaccine strategies. PMID:19811313

Caputo, Antonella; Gavioli, Riccardo; Bellino, Stefania; Longo, Olimpia; Tripiciano, Antonella; Francavilla, Vittorio; Sgadari, Cecilia; Paniccia, Giovanni; Titti, Fausto; Cafaro, Aurelio; Ferrantelli, Flavia; Monini, Paolo; Ensoli, Fabrizio; Ensoli, Barbara

2009-01-01

190

Possible false-negative results on therapeutic drug monitoring of phenytoin using a particle enhanced turbidimetric inhibition immunoassay in a patient with a high level of IgM.  

PubMed

: In this report, the authors described the unusual case of a patient in whom the plasma phenytoin concentration was unexpectedly not detected on a particle-enhanced turbidimetric inhibition immunoassay (PETINIA) technique, a typical immunoassay for phenytoin. The plasma concentration was measured using PETINIA and high-performance liquid chromatography in a 69-year-old male patient treated with fosphenytoin intravenously at the standard dose for 7 days. Although the plasma concentration of phenytoin was below the limit of detection (<0.5 mcg/mL) on PETINIA after the administration of fosphenytoin, the trough plasma concentration was estimated to be between 5 and 10 mg/L on high-performance liquid chromatography. When the plasma concentrations of IgM and IgG were measured using an enzyme-linked immunosorbent assay, the plasma IgG level was within the reference range, whereas the plasma IgM level was 2-3 times higher than the upper limit of the reference range. We concluded that the PETINIA method yielded a possible false-negative result regarding the phenytoin level in this patient, perhaps because of some hindrance to the measurement process by IgM. This case suggests that false-negative results should be considered when therapeutic drug monitoring reveals abnormally low values using PETINIA and that it is necessary to evaluate the plasma IgM level. PMID:24632808

Hirata, Kenshiro; Saruwatari, Junji; Enoki, Yuhuki; Iwata, Kazufumi; Urata, Yukino; Aizawa, Keiji; Ueda, Kentaro; Shirouzono, Takumi; Imamura, Motoki; Moriuchi, Hiroshi; Ishima, Yu; Kadowaki, Daisuke; Watanabe, Hiroshi; Hirata, Sumio; Maruyama, Toru; Fukunaga, Eiko

2014-10-01

191

HIV Incidence  

MedlinePLUS

... 4.2 times that of females (7.3). Blacks/African Americans Blacks/African Americans continue to be disproportionately affected by HIV infection. The estimated rate of new HIV infections among blacks/African Americans (68.9) was 7.9 times ...

192

Myocardial and pericardial disease in HIV  

Microsoft Academic Search

Opinion statement  Cardiovascular complications are frequently encountered in the HIV-infected population. Cardiac care providers should implement\\u000a appropriate preventive, screening, and therapeutic strategies to maximize survival and quality of life in this increasingly\\u000a treatable, chronic disease. All HIV-infected individuals should undergo periodic cardiac evaluation, including echocardiography,\\u000a in order to identify subclinical cardiac dysfunction. Left ventricular (LV) dysfunction can result from, or be

William G. Harmon; Gul H. Dadlani; Stacy D. Fisher; Steven E. Lipshultz

2002-01-01

193

Pharmacologic prevention of perinatal HIV infection.  

PubMed

The goal of antiretroviral therapy for the prevention of mother-to-child transmission (PMTCT) of HIV is to achieve maximal suppression of maternal viral load with minimal maternal, fetal and infant toxicity during pregnancy, delivery and postpartum. In addition to the efficacy and toxicity of antiretroviral therapy, the consideration of HIV resistance in mothers and infected newborns further complicates therapeutic choices for PMTCT. This manuscript summarizes current approaches to PMTC in diverse international settings. PMID:24709447

Rakhmanina, Natella Y; van den Anker, Johannes N

2014-03-01

194

A novel approach to develop anti-HIV drugs: adapting non-nucleoside anticancer chemotherapeutics  

Microsoft Academic Search

Some anticancer drugs, but not all, inhibit replication of human immunodeficiency virus (HIV) and thus, exhibit a therapeutic potential. Such drugs, unlike the traditional HIV enzyme inhibitors, could suppress HIV strains that are resistant to inhibitors of viral enzymes, decrease proviral burden in vivo, or reduce reservoirs of infection via killing infected cells. Thus, they may be an effective adjunct

M. Reza Sadaie; Ronald Mayner; Jay Doniger

2004-01-01

195

Protection of cells against HIV infection by the dialyzable leukocyte extract prior to cell culture duplication  

Microsoft Academic Search

The search for new therapeutic agents to treat the acquired immunodeficiency syndrome (AIDS) continues, since therapeutic anti-retroviral combinations already employed to treat AIDS patients do not eradicate the human immunodeficiency virus (HIV) infection. Our group recently demonstrated the inhibitory effect of the Dialyzable Leukocyte Extract (DLE) on HIV replication in cells, by using an in vitro assay system in the

Celia Fernández-Ortega; Marta Dubed; Giselle Álvarez; Leonor Navea; Dionne Casillas; Anna Ramírez; Leonor Lobaina; Taimí Paneque; Enrique Noa; Investigaciones Biomédicas

2008-01-01

196

Case management of HIV-infected severely malnourished children: challenges in the area of highest prevalence  

Microsoft Academic Search

In the ideal situation, use of WHO therapeutic guidelines for management of severe mal- nutrition 5 and a continuum of care for malnourished chil- dren 6 through community therapeutic care programmes would successfully improve survival in children without HIV infection. An alarming consequence of the HIV epidemic is an increase in the need by severely malnourished, seriously ill children for

Geert Tom Heikens; James Bunn FRCPCH; Beatrice Amadi MMedPaeds; Meera Chhagan FCPaed; James A Berkley MRCP; Nigel Rollins FRCPCH; Paul Kelly FRCP; Kathryn Maitland MRCP; Andrew Tomkins FMedSci

2008-01-01

197

HIV and Rheumatic Disease  

MedlinePLUS

... Patient Resources > Diseases & Conditions Back to Diseases & Conditions HIV and Rheumatic Disease PRINT Download PDF HIV infection ... treatment and HIV infection all overlap. What are HIV-associated rheumatic diseases? Some diseases of the joints ...

198

HIV and Your Heart  

MedlinePLUS

... Pressure High Blood Pressure Tools & Resources Stroke More HIV and Your Heart Banner 1 - HIV and Your ... Commercial support for this program was provided by HIV Wellness Checklist People living with HIV have even ...

199

HIV Treatment: The Basics  

MedlinePLUS

... with HIV live longer, healthier lives. How do HIV medicines work? HIV attacks and destroys the infection- ... to sexual partners. What are risks of taking HIV medicines? Potential risks of ART include side effects ...

200

HIV Transmission  

PubMed Central

HIV-1 is transmitted by sexual contact across mucosal surfaces, by maternal-infant exposure, and by percutaneous inoculation. For reasons that are still incompletely understood, CCR5-tropic viruses (R5 viruses) are preferentially transmitted by all routes. Transmission is followed by an orderly appearance of viral and host markers of infection in the blood plasma. In the acute phase of infection, HIV-1 replicates exponentially and diversifies randomly, allowing for an unambiguous molecular identification of transmitted/founder virus genomes and a precise characterization of the population bottleneck to virus transmission. Sexual transmission of HIV-1 most often results in productive clinical infection arising from a single virus, highlighting the extreme bottleneck and inherent inefficiency in virus transmission. It remains to be determined if HIV-1 transmission is largely a stochastic process whereby any reasonably fit R5 virus can be transmitted or if there are features of transmitted/founder viruses that facilitate their transmission in a biologically meaningful way. Human tissue explant models of HIV-1 infection and animal models of SIV/SHIV/HIV-1 transmission, coupled with new challenge virus strains that more closely reflect transmitted/founder viruses, have the potential to elucidate fundamental mechanisms in HIV-1 transmission relevant to vaccine design and other prevention strategies. PMID:23043157

Shaw, George M.; Hunter, Eric

2012-01-01

201

Proviral HIV-genome-wide and pol-gene specific Zinc Finger Nucleases: Usability for targeted HIV gene therapy  

PubMed Central

Background Infection with HIV, which culminates in the establishment of a latent proviral reservoir, presents formidable challenges for ultimate cure. Building on the hypothesis that ex-vivo or even in-vivo abolition or disruption of HIV-gene/genome-action by target mutagenesis or excision can irreversibly abrogate HIV's innate fitness to replicate and survive, we previously identified the isoschizomeric bacteria restriction enzymes (REases) AcsI and ApoI as potent cleavers of the HIV-pol gene (11 and 9 times in HIV-1 and 2, respectively). However, both enzymes, along with others found to cleave across the entire HIV-1 genome, slice (SX) at palindromic sequences that are prevalent within the human genome and thereby pose the risk of host genome toxicity. A long-term goal in the field of R-M enzymatic therapeutics has thus been to generate synthetic restriction endonucleases with longer recognition sites limited in specificity to HIV. We aimed (i) to assemble and construct zinc finger arrays and nucleases (ZFN) with either proviral-HIV-pol gene or proviral-HIV-1 whole-genome specificity respectively, and (ii) to advance a model for pre-clinically testing lentiviral vectors (LV) that deliver and transduce either ZFN genotype. Methods and Results First, we computationally generated the consensus sequences of (a) 114 dsDNA-binding zinc finger (Zif) arrays (ZFAs or ZifHIV-pol) and (b) two zinc-finger nucleases (ZFNs) which, unlike the AcsI and ApoI homeodomains, possess specificity to >18 base-pair sequences uniquely present within the HIV-pol gene (ZifHIV-polFN). Another 15 ZFNs targeting >18 bp sequences within the complete HIV-1 proviral genome were constructed (ZifHIV-1FN). Second, a model for constructing lentiviral vectors (LVs) that deliver and transduce a diploid copy of either ZifHIV-polFN or ZifHIV-1FN chimeric genes (termed LV- 2xZifHIV-polFN and LV- 2xZifHIV-1FN, respectively) is proposed. Third, two preclinical models for controlled testing of the safety and efficacy of either of these LVs are described using active HIV-infected TZM-bl reporter cells (HeLa-derived JC53-BL cells) and latent HIV-infected cell lines. Conclusion LV-2xZifHIV-polFN and LV- 2xZifHIV-1FN may offer the ex-vivo or even in-vivo experimental opportunity to halt HIV replication functionally by directly abrogating HIV-pol-gene-action or disrupting/excising over 80% of the proviral HIV DNA from latently infected cells. PMID:21781315

2011-01-01

202

Inhibition of HIV Fusion with Multivalent Gold Nanoparticles  

PubMed Central

The design and synthesis of a multivalent gold nanoparticle therapeutic is presented. SDC-1721, a fragment of the potent HIV inhibitor TAK-779, was synthesized and conjugated to 2.0 nm diameter gold nanoparticles. Free SDC-1721 had no inhibitory effect on HIV infection; however, the (SDC-1721)-gold nanoparticle conjugates displayed activity comparable to that of TAK-779. This result suggests that multivalent presentation of small molecules on gold nanoparticle surfaces can convert inactive drugs into potent therapeutics. PMID:18473457

Bowman, Mary-Catherine; Ballard, T. Eric; Ackerson, Christopher J.; Feldheim, Daniel L.; Margolis, David M.; Melander, Christian

2010-01-01

203

Basic HIV/AIDS Statistics  

MedlinePLUS

... you. Enter ZIP code or city Follow HIV/AIDS CDC HIV CDC HIV/AIDS See RSS | Subscribe ... Get Email Updates on HIV Anonymous Feedback HIV/AIDS Media Infographics Syndicated Content Podcasts Slide Sets HIV/ ...

204

Impact of Multi-Targeted Antiretroviral Treatment on Gut T Cell Depletion and HIV Reservoir Seeding during Acute HIV Infection  

Microsoft Academic Search

BackgroundLimited knowledge exists on early HIV events that may inform preventive and therapeutic strategies. This study aims to characterize the earliest immunologic and virologic HIV events following infection and investigates the usage of a novel therapeutic strategy.Methods and FindingsWe prospectively screened 24,430 subjects in Bangkok and identified 40 AHI individuals. Thirty Thais were enrolled (8 Fiebig I, 5 Fiebig II,

Jintanat Ananworanich; Alexandra Schuetz; Claire Vandergeeten; Irini Sereti; Mark de Souza; Rungsun Rerknimitr; Robin Dewar; Mary Marovich; Frits van Griensven; Rafick Sekaly; Suteeraporn Pinyakorn; Nittaya Phanuphak; Rapee Trichavaroj; Wiriya Rutvisuttinunt; Nitiya Chomchey; Robert Paris; Sheila Peel; Victor Valcour; Frank Maldarelli; Nicolas Chomont; Nelson Michael; Praphan Phanuphak; Jerome H. Kim

2012-01-01

205

Role of calmodulin in HIV-potentiated Fas-mediated apoptosis.  

PubMed Central

The recently demonstrated extraordinary rate of turnover of T cells in human immunodeficiency virus (HIV)-1-infected patients and the apparently concomitant high rate of viral production and death are consistent with a large amount of cell death directly due to infection. Apoptosis may be one of the major forms of T cell death in HIV-1 infection. Many apoptotic pathways depend on calcium and therefore would be expected to involve calmodulin. As the HIV-1 envelope glycoprotein, gp160, contains two known calmodulin-binding domains, we investigated the possibility that the cytoplasmic domain of the HIV-1 envelope protein gp160 could enhance Fas-mediated apoptosis, the major form of apoptosis in lymphocytes. Our studies have shown that 1) transfection of H9 and MOLT-4 cells with a non-infectious HIV proviral clone, pFN, which expresses wild-type gp160, leads to enhanced Fas-mediated apoptosis, 2) transfection of MOLT-4 cells with a pFN construct pFN delta 147, which expresses a carboxyl-terminally truncated gp160 lacking the calmodulin-binding domains, produces less Fas-mediated apoptosis than transfection with pFN, and 3) the calmodulin antagonists trifluoperazine and tamoxifen completely inhibit the pFN enhancement of Fas-mediated apoptosis in MOLT-4 cells. We have replicated all of these results using the vectors pSRHS and pSRHS delta 147, which express wild-type gp160 and truncated gp160, respectively, in the absence of other viral proteins. These investigations provide a mechanism by which HIV-1 may induce apoptosis and a possible intracellular target for future therapeutics. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 PMID:8780394

Pan, Z.; Radding, W.; Zhou, T.; Hunter, E.; Mountz, J.; McDonald, J. M.

1996-01-01

206

Newer gene editing technologies toward HIV gene therapy.  

PubMed

Despite the great success of highly active antiretroviral therapy (HAART) in ameliorating the course of HIV infection, alternative therapeutic approaches are being pursued because of practical problems associated with life-long therapy. The eradication of HIV in the so-called "Berlin patient" who received a bone marrow transplant from a CCR5-negative donor has rekindled interest in genome engineering strategies to achieve the same effect. Precise gene editing within the cells is now a realistic possibility with recent advances in understanding the DNA repair mechanisms, DNA interaction with transcription factors and bacterial defense mechanisms. Within the past few years, four novel technologies have emerged that can be engineered for recognition of specific DNA target sequences to enable site-specific gene editing: Homing Endonuclease, ZFN, TALEN, and CRISPR/Cas9 system. The most recent CRISPR/Cas9 system uses a short stretch of complementary RNA bound to Cas9 nuclease to recognize and cleave target DNA, as opposed to the previous technologies that use DNA binding motifs of either zinc finger proteins or transcription activator-like effector molecules fused to an endonuclease to mediate sequence-specific DNA cleavage. Unlike RNA interference, which requires the continued presence of effector moieties to maintain gene silencing, the newer technologies allow permanent disruption of the targeted gene after a single treatment. Here, we review the applications, limitations and future prospects of novel gene-editing strategies for use as HIV therapy. PMID:24284874

Manjunath, N; Yi, Guohua; Dang, Ying; Shankar, Premlata

2013-11-01

207

Adolescents with HIV and facial lipoatrophy: response to facial stimulation  

PubMed Central

OBJECTIVES: This study evaluated the effects of facial stimulation over the superficial muscles of the face in individuals with facial lipoatrophy associated with human immunodeficiency virus (HIV) and with no indication for treatment with polymethyl methacrylate. METHOD: The study sample comprised four adolescents of both genders ranging from 13 to 17 years in age. To participate in the study, the participants had to score six or less points on the Facial Lipoatrophy Index. The facial stimulation program used in our study consisted of 12 weekly 30-minute sessions during which individuals received therapy. The therapy consisted of intra- and extra-oral muscle contraction and stretching maneuvers of the zygomaticus major and minor and the masseter muscles. Pre- and post-treatment results were obtained using anthropometric static measurements of the face and the Facial Lipoatrophy Index. RESULTS: The results suggest that the therapeutic program effectively improved the volume of the buccinators. No significant differences were observed for the measurements of the medial portion of the face, the lateral portion of the face, the volume of the masseter muscle, or Facial Lipoatrophy Index scores. CONCLUSION: The results of our study suggest that facial maneuvers applied to the superficial muscles of the face of adolescents with facial lipoatrophy associated with HIV improved the facial area volume related to the buccinators muscles. We believe that our results will encourage future research with HIV patients, especially for patients who do not have the possibility of receiving an alternative aesthetic treatment. PMID:25141118

Gabana-Silveira, Jesus Claudio; Mangilli, Laura Davison; Sassi, Fernanda C.; Braga, Arnaldo Feitosa; Andrade, Claudia Regina Furquim

2014-01-01

208

Newer Gene Editing Technologies toward HIV Gene Therapy  

PubMed Central

Despite the great success of highly active antiretroviral therapy (HAART) in ameliorating the course of HIV infection, alternative therapeutic approaches are being pursued because of practical problems associated with life-long therapy. The eradication of HIV in the so-called “Berlin patient” who received a bone marrow transplant from a CCR5-negative donor has rekindled interest in genome engineering strategies to achieve the same effect. Precise gene editing within the cells is now a realistic possibility with recent advances in understanding the DNA repair mechanisms, DNA interaction with transcription factors and bacterial defense mechanisms. Within the past few years, four novel technologies have emerged that can be engineered for recognition of specific DNA target sequences to enable site-specific gene editing: Homing Endonuclease, ZFN, TALEN, and CRISPR/Cas9 system. The most recent CRISPR/Cas9 system uses a short stretch of complementary RNA bound to Cas9 nuclease to recognize and cleave target DNA, as opposed to the previous technologies that use DNA binding motifs of either zinc finger proteins or transcription activator-like effector molecules fused to an endonuclease to mediate sequence-specific DNA cleavage. Unlike RNA interference, which requires the continued presence of effector moieties to maintain gene silencing, the newer technologies allow permanent disruption of the targeted gene after a single treatment. Here, we review the applications, limitations and future prospects of novel gene-editing strategies for use as HIV therapy. PMID:24284874

Manjunath, N.; Yi, Guohua; Dang, Ying; Shankar, Premlata

2013-01-01

209

Complement and HIV-I infection/HIV-associated neurocognitive disorders.  

PubMed

The various neurological complications associated with HIV-1 infection, specifically HIV-associated neurocognitive disorders (HAND) persist as a major public health burden worldwide. Despite the widespread use of anti-retroviral therapy, the prevalence of HAND is significantly high. HAND results from the direct effects of an HIV-1 infection as well as secondary effects of HIV-1-induced immune reaction and inflammatory response. Complement, a critical mediator of innate and acquired immunity, plays important roles in defeating many viral infections by the formation of a lytic pore or indirectly by opsonization and recruitment of phagocytes. While the role of complement in the pathogenesis of HIV-1 infection and HAND has been previously recognized for over 15 years, it has been largely underestimated thus far. Complement can be activated through HIV-1 envelope proteins, mannose-binding lectins (MBL), and anti-HIV-1 antibodies. Complement not only fights against HIV-1 infection but also enhances HIV-1 infection. In addition, HIV-1 can hijack complement regulators such as CD59 and CD55 and can utilize these regulators and factor H to escape from complement attack. Normally, complement levels in brain are much lower than plasma levels and there is no or little complement deposition in brain cells. Interestingly, local production and deposition of complement are dramatically increased in HIV-1-infected brain, indicating that complement may contribute to the pathogenesis of HAND. Here, we review the current understanding of the role of complement in HIV-1 infection and HAND, as well as potential therapeutic approaches targeting the complement system for the treatment and eradications of HIV-1 infection. PMID:24639397

Liu, Fengming; Dai, Shen; Gordon, Jennifer; Qin, Xuebin

2014-04-01

210

HIV-Associated Venous Thromboembolism  

PubMed Central

HIV infection has been recognized as a prothrombotic condition and this association has now been proven by a large number of studies with a reported VTE frequency among HIV-infected patients ranging from 0.19% to 7,63 %/year. HIV infection is associated with a two to tenfold increased risk of venous thrombosis in comparison with a general population of the same age. Some risk factors demonstrated a strongest association with VTE such as, low CD4+ cell count especially in the presence of clinical AIDS, protein S deficiency, and protein C deficiency. Whereas other risk factors are still controversial like protease inhibitor therapy, presence of active opportunistic infections and presence of antiphospholipid antibodies, including anticardiolipin antibodies and lupus anticoagulant. Physicians caring for HIV positive patients should be able to recognize and treat not only the well-known opportunistic infections and malignancies associated with this chronic disease, but also be alert to the less well-known complications such as thromboses. Pulmonary embolism should be included in the differential diagnosis when patients with HIV/AIDS have unexplained dyspnea or hypoxemia. In younger individuals with VTE, especially men, without other identifiable risk factors for VTE, HIV should be considered. Because interactions between warfarin and antiretrovirals is possible, health care providers should also be alert to the potential of dangerously high or low INRs when they are giving anticoagulants to patients with HIV infection who are undergoing antiretroviral therapy. PMID:21869916

Bibas, Michele; Biava, Gianluigi; Antinori., Andrea

2011-01-01

211

Relative resistance of HIV-1 founder viruses to control by interferon-alpha  

PubMed Central

Background Following mucosal human immunodeficiency virus type 1 (HIV-1) transmission, type 1 interferons (IFNs) are rapidly induced at sites of initial virus replication in the mucosa and draining lymph nodes. However, the role played by IFN-stimulated antiviral activity in restricting HIV-1 replication during the initial stages of infection is not clear. We hypothesized that if type 1 IFNs exert selective pressure on HIV-1 replication in the earliest stages of infection, the founder viruses that succeed in establishing systemic infection would be more IFN-resistant than viruses replicating during chronic infection, when type 1 IFNs are produced at much lower levels. To address this hypothesis, the relative resistance of virus isolates derived from HIV-1-infected individuals during acute and chronic infection to control by type 1 IFNs was analysed. Results The replication of plasma virus isolates generated from subjects acutely infected with HIV-1 and molecularly cloned founder HIV-1 strains could be reduced but not fully suppressed by type 1 IFNs in vitro. The mean IC50 value for IFN?2 (22 U/ml) was lower than that for IFN? (346 U/ml), although at maximally-inhibitory concentrations both IFN subtypes inhibited virus replication to similar extents. Individual virus isolates exhibited differential susceptibility to inhibition by IFN?2 and IFN?, likely reflecting variation in resistance to differentially up-regulated IFN-stimulated genes. Virus isolates from subjects acutely infected with HIV-1 were significantly more resistant to in vitro control by IFN? than virus isolates generated from the same individuals during chronic, asymptomatic infection. Viral IFN resistance declined rapidly after the acute phase of infection: in five subjects, viruses derived from six-month consensus molecular clones were significantly more sensitive to the antiviral effects of IFNs than the corresponding founder viruses. Conclusions The establishment of systemic HIV-1 infection by relatively IFN?-resistant founder viruses lends strong support to the hypothesis that IFN? plays an important role in the control of HIV-1 replication during the earliest stages of infection, prior to systemic viral spread. These findings suggest that it may be possible to harness the antiviral activity of type 1 IFNs in prophylactic and potentially also therapeutic strategies to combat HIV-1 infection. PMID:24299076

2013-01-01

212

Cocaine abuse and HIV1 infection: Epidemiology and neuropathogenesis  

Microsoft Academic Search

The epidemiology of cocaine abuse and potential relationships of cocaine withdrawal to human immunodeficiency virus type 1 (HIV-1)-associated dementia (HAD) are discussed. Neuroendocrinological changes in HIV-1 infection of the central nervous system (CNS) are discussed with the relevant impact of cocaine abuse. HIV-1 load in the brain tissue of infected substance users is described along with possible associations with neuropathology

Karl Goodkin; Paul Shapshak; Lisa R Metsch; Clyde B McCoy; Keith A Crandall; Mahendra Kumar; Robert K Fujimura; Virginia McCoy; Bao Tong Zhang; Svetlana Reyblat; Ke-Qin Xin; Adarsh M Kumar

1998-01-01

213

HIV and AIDS  

NSDL National Science Digital Library

The Science Inside: HIV and AIDSThis booklet helps to explain what doctors and scientists know about the HIV and AIDS epidemic. It summarizes what HIV and AIDS are and what happens when HIV becomes AIDS, including the health problems that can result. The e-book explains how the diseases are spread, what groups suffer most from them, how they may be prevented, how they are treated, and what the latest research reveals.The Science Inside e-book series is intended to be a bridge between the consumer health brochure and the scientific paper, the booklets in this series focus on the science that is inside of, or behind, the disease its cause, its possible cure, its treatment, promising research, and so on. These booklets are designed to appeal to people who have not had the opportunity to study the science and to understand why they may have been given some of the advice that they have been given through some of the more consumer-oriented materials.

American Association for the Advancement of Science (; )

2004-01-01

214

Undiagnosed HIV Presenting with Lymphoid Interstitial Pneumonitis  

PubMed Central

Undiagnosed or untreated human immunodeficiency virus infection can lead to devastating complications. We present a case of a 41-year-old woman who was found to have HIV-related lymphoid interstitial pneumonitis. LIP is uncommon, and its presentation can be quite similar to that of other chronic lung conditions. This case illustrates one of the possible protean manifestations of untreated HIV and is a sobering reminder of the need to screen all adults for HIV infection. Additionally, further invasive diagnostic testing may be required to guide therapy in patients with advanced acquired immune deficiency syndrome. This patient's LIP was likely related to long-standing unrecognized HIV disease. PMID:22567465

Rizqallah, Jason J.; Shah, Christopher T.; Oluwole, Oladoyin; Sheagren, John N.

2011-01-01

215

Nanotechnology: A magic bullet for HIV AIDS treatment.  

PubMed

Human immunode?ciency virus (HIV) infection has become devastating in last a few years. Nearly 7400 new infection cases are coming every day. Highly active antiretroviral therapy (HAART), which involves combination of at least three antiretroviral (ARV) drugs, has been used to extend the life span of the HIV-infected patients. HAART has played an important role to reduce mortality rate in the developed countries but in the developing countries condition is still worst with millions of people being infected by this disease. For the improvement of the situation, nanotechnology-based drug system has been explored for the HIV therapeutics. Nanosystems used for HIV therapeutics offer some unique advantage like enhancement of bioavailability, water solubility, stability, and targeting ability of ARV drugs. Main nanotechnology-based systems explored for HIV therapeutics are liposomes, nanoparticles, niosomes, polymeric micelles, and dendrimers. Present manuscript reviews conventional method of HIV therapeutics and recent advances in the eld of nanotechnology-based systems for treatment of HIV-AIDS. PMID:24564348

Kumar, Lalit; Verma, Shivani; Prasad, Deo Nandan; Bhardwaj, Ankur; Vaidya, Bhuvaneshwar; Jain, Amit Kumar

2015-04-01

216

Herpes simplex virus type-2 stimulates HIV-1 replication in cervical tissues: implications for HIV-1 transmission and efficacy of anti-HIV-1 microbicides.  

PubMed

Herpes Simplex virus Type-2 (HSV-2) increases the risk of HIV-1 acquisition, yet the mechanism for this viral pathogen to regulate the susceptibility of the cervicovaginal mucosa to HIV-1 is virtually unknown. Using ex vivo human ectocervical tissue models, we report greater levels of HIV-1 reverse transcription, DNA integration, RNA expression, and virions release in HIV-1/HSV-2 co-infected tissues compared with HIV-1 only infected tissues (P<0.05). Enhanced HIV-1 replication was associated with increased CD4, CCR5, and CD38 transcription (P<0.05) and increased number of CD4(+)/CCR5(+)/CD38(+) T cells in HIV-1/HSV-2 co-infected tissues compared with tissues infected with HIV-1 alone. Tenofovir (TFV) 1% gel, the leading microbicide candidate, demonstrated only partial protection against HIV-1, when applied vaginally before and after sexual intercourse. It is possible that mucosal inflammation, in particular that induced by HSV-2 infection, may have decreased TFV efficacy. HSV-2 upregulated the number of HIV-1-infected cells and elevated the concentration of TFV needed to decrease HIV-1 infection. Similarly, only high concentrations of TFV inhibited HSV-2 replication in HIV-1/HSV-2-infected tissues. Thus, HSV-2 co-infection and mucosal immune cell activation should be taken into consideration when designing preventative strategies for sexual transmission of HIV-1. PMID:24496317

Rollenhagen, C; Lathrop, M J; Macura, S L; Doncel, G F; Asin, S N

2014-09-01

217

A plasmid DNA immunogen expressing fifteen protein antigens and complex virus-like particles (VLP+) mimicking naturally occurring HIV.  

PubMed

We describe here a single plasmid DNA immunogen representing the broadest antigen repertoire among HIV vaccine candidates. This pDNA was "ANTIGENeered" for the regulated expression of thirteen complete and two non-functional HIV protein antigens. These proteins self assemble into complex virus-like particles (VLP(+)). Multiple irreversible safety features were introduced by genetic modifications including the complete impairment of integration, reverse transcription, the function of Nef and the 3'LTR. Epitope analysis predicted that the pDNA-derived protein repertoire can potentially present over 3000 T cell epitopes. However, the expressed antigens have different potential to induce HIV-specific CD4(+) and CD8(+) T cells supporting our hypothesis that HIV vaccines should contain all possible regulatory and structural proteins. This immunogen is the active pharmaceutical ingredient of DermaVir, a therapeutic vaccine product candidate that recently successfully completed Phase II clinical trials and meets the safety, immunogenicity and cost requirements of an HIV vaccine. PMID:21109034

Somogyi, Eszter; Xu, Jianqing; Gudics, Agnes; Tóth, József; Kovács, Attila L; Lori, Franco; Lisziewicz, Julianna

2011-01-17

218

[HIV tests].  

PubMed

In the care and treatment of HIV-infected patients, several laboratory methods are indispensable. The diagnosis of HIV infection is established by one of the following methods: detecting antibodies to the virus; detecting the viral p24 antigen; detecting viral nucleic acid; or culturing HIV. The most widely used test is the detection of antibodies to HIV. Rapid serological tests take only 15 minutes for all procedures and are very useful in clinical settings. The rapid saliva test has also been developed, but is not available in Japan. Recently, some serological test kits have become commercially available via websites. Thus, people can perform tests by themselves without visiting testing facilities, with samples being sent by post. The CD4 T-cell count is the most important marker to determine when to start anti-HIV drugs. In addition, resistance testing should be used to guide the selection of the antiretroviral regimen in both treatment-naďve and -experienced patients. The following tests are still experimental but very important: HLA-B*5701 testing should be performed prior to the initiation of abacavir. Recent studies have revealed that HLA-B*5701 is strongly associated with the abacavir hypersensitivity reaction. However, fortunately, Japanese rarely have HLA-B*5701. The viral tropism assay should be performed prior to the initiation of the CCR5 antagonist. PMID:19086458

Yoshimura, Yukihiro; Techikawa, Natsuo

2008-11-01

219

Structure of the HIV1 Integrase Catalytic Domain Complexed with an Inhibitor: A Platform for Antiviral Drug Design  

Microsoft Academic Search

HIV integrase, the enzyme that inserts the viral DNA into the host chromosome, has no mammalian counterpart, making it an attractive target for antiviral drug design. As one of the three enzymes produced by HIV, it can be expected that inhibitors of this enzyme will complement the therapeutic use of HIV protease and reverse transcriptase inhibitors. We have determined the

Yehuda Goldgur; Robert Craigie; Gerson H. Cohen; Tamio Fujiwara; Tomokazu Yoshinaga; Toshio Fujishita; Hirohiko Sugimoto; Takeshi Endo; Hitoshi Murai; David R. Davies

1999-01-01

220

HIV/AIDS  

MedlinePLUS

... prevention, diagnosis, treatment and care for key populations Global health sector strategy on HIV/AIDS 2011-2015 More about HIV/AIDS 15 facts on HIV treatment scale-up and the new WHO ARV guidelines 2013 WHO's work on HIV/AIDS More about HIV/AIDS: topical overview

221

Financing of U.S. Biomedical Research and New Drug Approvals across Therapeutic Areas  

Microsoft Academic Search

BackgroundWe estimated U.S. biomedical research funding across therapeutic areas, determined the association with disease burden, and evaluated new drug approvals that resulted from this investment.Methodology\\/Principal FindingsWe calculated funding from 1995 to 2005 and totaled Food and Drug Administration approvals in eight therapeutic areas (cardiovascular, endocrine, gastrointestinal, genitourinary, HIV\\/AIDS, infectious disease excluding HIV, oncology, and respiratory) primarily using public data. We

E. Ray Dorsey; Joel P. Thompson; Melisa Carrasco; Jason de Roulet; Philip Vitticore; Sean Nicholson; S. Claiborne Johnston; Robert G. Holloway; Hamilton Moses; Pedro R. Lowenstein

2009-01-01

222

Anti-HIV designer T cells progressively eradicate a latently infected cell line by sequentially inducing HIV reactivation then killing the newly gp120-positive cells.  

PubMed

The current antiretroviral therapy (ART) can effectively reduce plasma HIV loads to undetectable levels, but cannot eliminate latently infected resting memory CD4 T cells that persist for the lifetime of infected patients. Therefore, designing new therapeutic approaches to eliminate these latently infected cells or the cells that produce HIV upon reactivation from latency is a priority in the ART era in order to progress to a cure of HIV. Here, we show that "designer" T cells expressing chimeric antigen receptor (CAR), CD4-CD28-CD3?, can target and kill HIV Env-expressing cells. Further, they secrete effector cytokines upon contact with HIV Env+ target cells that can reactivate latent HIV in a cell line model, thereby exposing those cells to recognition and killing by anti-HIV CAR+ T cells. Taken to the limit, this process could form the basis for an eventual functional or sterilizing cure for HIV in patients. PMID:24074590

Sahu, Gautam K; Sango, Kaori; Selliah, Nithianandan; Ma, Qiangzhong; Skowron, Gail; Junghans, Richard P

2013-11-01

223

Body Shape Changes with HIV  

MedlinePLUS

... Diagnosed » Body Shape Changes with HIV: Entire Lession HIV/AIDS HIV/AIDS HIV/AIDS Home For Veterans ... Enter ZIP code here Body Shape Changes with HIV: Entire Lession for Veterans and the Public Body ...

224

Relative foster parents of HIV-affected children.  

PubMed

The HIV epidemic is one of the reasons for an increase in relative foster care. Most children of HIV-infected parents are not infected, but both the children and their caregivers are affected by the parent's illness. Twenty-eight caregivers participated in an exploratory, qualitative study of the permanency planning needs of HIV-affected relative foster parents. Of the caregivers, 17 disclosed that the foster child's parent was HIV-infected; 11 caregivers did not report HIV infection in the immediate family. HIV-affected caregivers' greatest need was a more adequate response from social workers and therapy services for the children; nonaffected caregivers needed financial assistance most. More HIV-affected caregivers were considering permanency than nonaffected caregivers. Child welfare workers and relative foster parents need training on HIV's effect on the families so that appropriate services can be accessed as early as possible. PMID:12109600

Mason, Sally; Linsk, Nathan

2002-01-01

225

HIV Vaccine Research: The Challenge and the Way Forward  

PubMed Central

Human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) is a worldwide epidemic, with over 35 million people infected currently. Therefore, the development of a safe and effective HIV-1 vaccine is on top of the global health priority. In the past few years, there have been many promising advances in the prevention of HIV/AIDS, among which the RV144 Thai trial has been encouraging and suggests optimization of the current vaccine strategies or search for novel strategies. Here we reviewed the brief history of HIV-1 vaccine, analyzed key challenges existing now, and illustrated future research priority/directions for a therapeutic or prophylactic HIV-1 vaccine, with the hope of accelerating the speed of vaccine development. We believe that an effective HIV-1 vaccine, together with other prevention approaches, will bring an end to this epidemic in the near future.

Wang, Hai-Bo; Mo, Qiu-Hua; Yang, Ze

2015-01-01

226

Vector replication and expression of HIV-1 antigens by the HIV/AIDS vaccine candidate MVA-B is not affected by HIV-1 protease inhibitors.  

PubMed

MVA-B is an attenuated poxvirus vector expressing human immunodeficiency virus type 1 Env, Gag, Pol, and Nef antigens from clade B, and is considered a promising HIV/AIDS vaccine candidate. Recently, a phase I clinical trial in human healthy volunteers has shown that MVA-B is safe and highly immunogenic, inducing broad, polyfunctional, and long-lasting CD4(+) and CD8(+) T cell responses to HIV-1 antigens, with preference for effector memory T cells; and it also triggers the induction of specific antibodies to Env in most of the vaccines. While MVA recombinants expressing HIV-1 antigens are being used or plan to use in therapeutic clinical trials, little is known on the effect of HIV-1 highly active antiretroviral therapy in MVA life cycle. To define this role, here we have evaluated in established cell cultures and human dendritic cells to what extent different HIV-1 protease inhibitors affect virus replication and expression of HIV-1 antigens during MVA-B infection. The results obtained revealed that the most commonly used HIV-1 protease inhibitors (atazanavir, ritonavir, and lopinavir) had no effect on MVA-B virus growth kinetics, even at higher concentrations than those normally used on HAART. Furthermore, expression of gp120 and the fused Gag-Pol-Nef polyprotein in permissive and non-permissive cells infected with MVA-B were also not affected. These findings are relevant information for the therapeutic use of MVA-B as an HIV-1/AIDS vaccine. PMID:22659488

García-Arriaza, Juan; Arnáez, Pilar; Jiménez, José Luis; Gómez, Carmen E; Muńoz-Fernández, María Ángeles; Esteban, Mariano

2012-08-01

227

Aptamer-siRNA Chimeras for HIV.  

PubMed

Since 1980s, HIV/AIDS has escalated into a global pandemic. Although combinatorial antiretroviral therapy (cART) regimens can suppress plasma virus levels to below the detection limit and the survival rate of HIV-1 infected patients has been improving, long-term cART holds the potential to cause a number of chronic diseases. RNA interference (RNAi) is considered as a powerful method for developing new generation of therapeutics. Discovery of small interfering RNAs (siRNAs) shed light on limitations of targets that are "undruggable" with current technologies. However, delivery remains a major hurdle of siRNA-based therapy. Recent progress in technology of engineering nucleic acid enables a targeted delivery of siRNAs using aptamers, which, as often regarded as nucleic acid "antibodies," can recognize/bind to multiple different proteins and small-molecule targets by forming scaffolds for molecular interactions. SELEX technology enabled to isolate highly target specific aptamers from a random sequence oligonucleotide library. A number of aptamers for HIV-1 proteins as well as host proteins that interact with HIV-1 have been developed and some of them have potent viral neutralization ability and inhibition of HIV-1 infectivity. The availability of these aptamers has given an idea of using aptamers for targeting delivery of siRNAs. So far, aptamers against either HIV-1 gp120 or CD4 have been eagerly evaluated as the aptamer portion of the aptamer-siRNA chimeras for the treatment or prevention of HIV-1. In this chapter, we highlight the development and therapeutic potential of aptamer-siRNA chimeras for HIV-1. PMID:25757623

Takahashi, Mayumi; Burnett, John C; Rossi, John J

2015-01-01

228

The pharmacology of TUG-891, a potent and selective agonist of the free fatty acid receptor 4 (FFA4/GPR120), demonstrates both potential opportunity and possible challenges to therapeutic agonism.  

PubMed

TUG-891 [3-(4-((4-fluoro-4'-methyl-[1,1'-biphenyl]-2-yl)methoxy)phenyl)propanoic acid] was recently described as a potent and selective agonist for the long chain free fatty acid (LCFA) receptor 4 (FFA4; previously G protein-coupled receptor 120, or GPR120). Herein, we have used TUG-891 to further define the function of FFA4 and used this compound in proof of principle studies to indicate the therapeutic potential of this receptor. TUG-891 displayed similar signaling properties to the LCFA ?-linolenic acid at human FFA4 across various assay end points, including stimulation of Ca˛? mobilization, ?-arrestin-1 and ?-arrestin-2 recruitment, and extracellular signal-regulated kinase phosphorylation. Activation of human FFA4 by TUG-891 also resulted in rapid phosphorylation and internalization of the receptor. While these latter events were associated with desensitization of the FFA4 signaling response, removal of TUG-891 allowed both rapid recycling of FFA4 back to the cell surface and resensitization of the FFA4 Ca˛? signaling response. TUG-891 was also a potent agonist of mouse FFA4, but it showed only limited selectivity over mouse FFA1, complicating its use in vivo in this species. Pharmacologic dissection of responses to TUG-891 in model murine cell systems indicated that activation of FFA4 was able to mimic many potentially beneficial therapeutic properties previously reported for LCFAs, including stimulating glucagon-like peptide-1 secretion from enteroendocrine cells, enhancing glucose uptake in 3T3-L1 adipocytes, and inhibiting release of proinflammatory mediators from RAW264.7 macrophages, which suggests promise for FFA4 as a therapeutic target for type 2 diabetes and obesity. Together, these results demonstrate both potential but also significant challenges that still need to be overcome to therapeutically target FFA4. PMID:23979972

Hudson, Brian D; Shimpukade, Bharat; Mackenzie, Amanda E; Butcher, Adrian J; Pediani, John D; Christiansen, Elisabeth; Heathcote, Helen; Tobin, Andrew B; Ulven, Trond; Milligan, Graeme

2013-11-01

229

Sexual health for people living with HIV.  

PubMed

Sexual health is defined in terms of well-being, but is challenged by the social, cultural and economic realities faced by women and men with HIV. A sexual rights approach puts women and men with HIV in charge of their sexual health. Accurate, accessible information to make informed choices and safe, pleasurable sexual relationships possible is best delivered through peer education and health professionals trained in empathetic approaches to sensitive issues. Young people with HIV especially need appropriate sex education and support for dealing with sexuality and self-identity with HIV. Women and men with HIV need condoms, appropriate services for sexually transmitted infections, sexual dysfunction and management of cervical and anogenital cancers. Interventions based on positive prevention, that combine protection of personal health with avoiding HIV/STI transmission to partners, are recommended. HIV counselling following a positive test has increased condom use and decreased coercive sex and outside sexual contacts among discordant couples. HIV treatment and care have reduced stigma and increased uptake of HIV testing and disclosure of positive status to partners. High adherence to antiretroviral therapy and safer sexual behaviour must go hand-in-hand. Sexual health services have worked with peer educators and volunteer groups to reach those at higher risk, such as sex workers. Technological advances in diagnosis of STIs, microbicide development and screening and vaccination for human papillomavirus must be available in developing countries and for those with the highest need globally. PMID:17531749

Shapiro, Kathy; Ray, Sunanda

2007-05-01

230

HIV-related neuropathy: current perspectives  

PubMed Central

Distal symmetric polyneuropathy (DSP) related to human immunodeficiency virus (HIV) is one of the most common neurologic complications of HIV, possibly affecting as many as 50% of all individuals infected with HIV. Two potentially neurotoxic mechanisms have been proposed to play a crucial role in the pathogenesis of HIV DSP: neurotoxicity resulting from the virus and its products; as well as adverse neurotoxic effects of medications used in the treatment of HIV. Clinically, HIV DSP is characterized by a combination of signs and symptoms that include decreased deep tendon reflexes at the ankles and decreased sensation in the distal extremities as well as paresthesias, dysesthesias, and pain in a symmetric stocking–glove distribution. These symptoms are generally static or slowly progressive over time, and depending on the severity, may interfere significantly with the patient’s daily activities. In addition to the clinical picture, nerve conduction studies and skin biopsies are often pursued to support the diagnosis of HIV DSP. Anticonvulsants, antidepressants, topical agents, and nonspecific analgesics may help relieve neuropathic pain. Specifically, gabapentin, lamotrigine, pregabalin, amitriptyline, duloxetine, and high-dose topical capsaicin patches have been used in research and clinical practice. Further research is needed to elucidate the pathogenesis of HIV DSP, thus facilitating the development of novel treatment strategies. This review discusses the epidemiology, pathophysiology, clinical findings, diagnosis, and management of DSP in the setting of HIV. PMID:24049460

Schütz, Sonja G; Robinson-Papp, Jessica

2013-01-01

231

HIV-1 Latency in Monocytes/Macrophages  

PubMed Central

Human immunodeficiency virus type 1 (HIV-1) targets CD4+ T cells and cells of the monocyte/macrophage lineage. HIV pathogenesis is characterized by the depletion of T lymphocytes and by the presence of a population of cells in which latency has been established called the HIV-1 reservoir. Highly active antiretroviral therapy (HAART) has significantly improved the life of HIV-1 infected patients. However, complete eradication of HIV-1 from infected individuals is not possible without targeting latent sources of infection. HIV-1 establishes latent infection in resting CD4+ T cells and findings indicate that latency can also be established in the cells of monocyte/macrophage lineage. Monocyte/macrophage lineage includes among others, monocytes, macrophages and brain resident macrophages. These cells are relatively more resistant to apoptosis induced by HIV-1, thus are important stable hideouts of the virus. Much effort has been made in the direction of eliminating HIV-1 resting CD4+ T-cell reservoirs. However, it is impossible to achieve a cure for HIV-1 without considering these neglected latent reservoirs, the cells of monocyte/macrophage lineage. In this review we will describe our current understanding of the mechanism of latency in monocyte/macrophage lineage and how such cells can be specifically eliminated from the infected host. PMID:24759213

Kumar, Amit; Abbas, Wasim; Herbein, Georges

2014-01-01

232

Get Tested for HIV  

MedlinePLUS

... medical records. If you are worried about giving your name, you can get an anonymous HIV test at ... means that you don’t have to give your name. What is HIV? HIV stands for human immunodeficiency ...

233

Preventing HIV with Medicine  

MedlinePLUS

... information in Spanish ( en espańol ) Preventing HIV with medicine Get medicine right after you are exposed to ... to top More information on Preventing HIV with medicine Explore other publications and websites National HIV and ...

234

Travelers' Health: HIV Infection  

MedlinePLUS

... AGENT HIV, a single-stranded, positive-sense, enveloped RNA virus in the genus Lentivirus. TRANSMISSION HIV can ... be diagnosed is about 9 days, when HIV RNA becomes detectable in blood; however, the tests needed ...

235

Children and HIV  

MedlinePLUS

... U.S. Government Global AIDS Activities Global HIV/AIDS Organizations CIA HIV/AIDS Data National HIV/AIDS Strategy Overview Implementation Progress Using the Strategy Documents Videos PACHA About ...

236

Stages of HIV Infection  

MedlinePLUS

... U.S. Government Global AIDS Activities Global HIV/AIDS Organizations CIA HIV/AIDS Data National HIV/AIDS Strategy Overview Implementation Progress Using the Strategy Documents Videos PACHA About ...

237

[Diagnosing HIV in Switzerland].  

PubMed

The diagnosis "HIV infection" has severe consequences. False positive or false negative HIV results must be avoided. The Swiss Federal Office of Public Health generated a concept for HIV testing which also includes the characterization of HIV for optimal medical care of the HIV-infected patient. This concept requests that the following four questions are answered: 1. Is the patient indeed HIV-infected? 2. Is it HIV-1 or HIV-2, and if the patient is tested positive for HIV-1, what group, M or O? Are drug resistances present? 3. What is the HIV copy number in the blood? 4. What is the percentage of recent HIV-infections (< 12 months) among all tested positive test results? We also present a short summary how to approach the HIV-infected patient at the initial and subsequent visits. PMID:25093309

Schüpbach, Jörg; Berger, Christoph; Böni, Jürg; Speck, Roberto F

2014-08-01

238

HIV and AIDS  

MedlinePLUS

... Teens > Sexual Health > STDs & Other Infections > HIV and AIDS Print A A A Text Size What's in ... in human history. HIV causes a condition called acquired immunodeficiency syndrome — better known as AIDS . HIV destroys a type ...

239

HIV/AIDS  

MedlinePLUS

Human immunodeficiency virus (HIV) causes HIV infection and AIDS. The virus attacks the immune system. As the ... high-risk behaviors, are HIV-positive, or have AIDS People who received blood transfusions or clotting products ...

240

HIV and AIDS  

MedlinePLUS

... actually the virus that causes the disease AIDS. HIV Hurts the Immune System People who are HIV ... a serious infection. Continue How Many People Have HIV/AIDS? Since the discovery of the virus almost ...

241

Children and HIV  

MedlinePLUS

... Children Translate Text Size Print Children Children and HIV Most HIV-positive children under the age of ... Frequently Asked Questions How long do children with HIV typically live? Because effective treatments are relatively new ...

242

HIV/AIDS  

MedlinePLUS

HIV stands for human immunodeficiency virus. It kills or damages the body's immune system cells. AIDS stands ... is the most advanced stage of infection with HIV. HIV most often spreads through unprotected sex with ...

243

HIV/AIDS Basics  

MedlinePLUS

... About CDC.gov . Act Against AIDS Share Compartir HIV/AIDS Basics Before we can stop any epidemic, ... before, AIDS is still a significant health issue. HIV 101 HIV/AIDS Basic Statistics Transmission Testing Prevention ...

244

HIV and Pregnancy  

MedlinePLUS

... infection can be treated, but not cured. Taking anti-HIV drugs can help people with HIV infection stay healthy ... They include the following: • Take a combination of anti-HIV drugs during your pregnancy as prescribed. • Have your baby ...

245

Older People and HIV  

MedlinePLUS

... HIV in older people were done before strong anti-HIV drugs were available. Most of them showed that older ... it more difficult for a doctor to choose anti-HIV drugs because of interactions with other medications. MENTAL HEALTH ...

246

HIV-1 protease-induced apoptosis  

PubMed Central

Background Apoptosis is one of the presumptive causes of CD4+ T cell depletion during HIV infection and progression to AIDS. However, the precise role of HIV-1 in this process remains unexplained. HIV-1 protease (PR) has been suggested as a possible factor, but a direct link between HIV-1 PR enzymatic activity and apoptosis has not been established. Results Here, we show that expression of active HIV-1 PR induces death in HeLa and HEK-293 cells via the mitochondrial apoptotic pathway. This conclusion is based on in vivo observations of the direct localization of HIV-1 PR in mitochondria, a key player in triggering apoptosis. Moreover, we observed an HIV-1 PR concentration-dependent decrease in mitochondrial membrane potential and the role of HIV-1 PR in activation of caspase 9, PARP cleavage and DNA fragmentation. In addition, in vitro data demonstrated that HIV-1 PR mediates cleavage of mitochondrial proteins Tom22, VDAC and ANT, leading to release of AIF and Hsp60 proteins. By using yeast two-hybrid screening, we also identified a new HIV-1 PR interaction partner, breast carcinoma-associated protein 3 (BCA3). We found that BCA3 accelerates p53 transcriptional activity on the bax promoter, thus elevating the cellular level of pro-apoptotic Bax protein. Conclusion In summary, our results describe the involvement of HIV-1 PR in apoptosis, which is caused either by a direct effect of HIV-1 PR on mitochondrial membrane integrity or by its interaction with cellular protein BCA3. PMID:24886575

2014-01-01

247

DYNAMIC EQUILIBRIUM IN THERAPEUTIC SITUATIONS.  

ERIC Educational Resources Information Center

THE CONCEPT OF DYNAMIC EQUILIBRIUM IS USED TO EXAMINE THE OCCURRENCE OF CHANGE IN A THERAPEUTIC INTERVIEW AND TO PROPOSE A THEORY OF THERAPY. BY ANALYZING THE WORKINGS OF THE PSYCHOSOCIAL SYSTEM THROUGH THE GENERAL SYSTEMS THEORY, IT IS POSSIBLE TO SEE HOW CHANGE OCCURS IN AN INDIVIDUAL FAMILY OR COMMUNITY. APPLIED TO A FAMILY INTERVIEW, THE MODEL…

CARROLL, EDWARD J.

248

Therapeutic education of diabetic patients.  

PubMed

Therapeutic patient education is a patient-centred approach, focussed on patients' needs, resources, values and strategies. It allows patients to improve their knowledge and skills not only concerning their illness but also their treatment. It brings a better quality of life, a greater therapeutic compliance and a reduction in complications. The most difficult part of therapeutic patient education occurs when patients must change their behaviour. Motivational interviewing and cognitive-behavioural approaches contribute greatly here and allow both the preparation and support of patients during progressive 'step by step' change. The work on resistance to change is fundamental, and ambivalence when faced with the choice of a new way of life must be measured, discussed and negotiated. Patients become partners and we become 'coaches'. The negotiation of objectives must allow patients to choose their own strategies, which normally should cost them the least possible, psychologically, and bring them the maximum benefit. The efficiency of therapeutic patient education no longer needs to be proved: 80% less amputations over 10 years in diabetic patients; 50% maintenance of weight loss over 5 years, etc. In conclusion, therapeutic education is part of a humanistic medical approach centred on patients; it allows them to be active participants in their own treatment with the aim of improving their quality of life and therapeutic compliance, as well as reducing potential complications. Thus, health care professionals teach, inform, train, negotiate with, motivate and accompany patients in the long-term follow-up of their illness. PMID:18229887

Golay, A; Lagger, G; Chambouleyron, M; Carrard, I; Lasserre-Moutet, A

2008-01-01

249

Therapeutics Based On The Induced Internalization Of Surface Receptors  

Cancer.gov

The National Cancer Institute, Laboratory of Cellular Oncology is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize therapeutics for diseases or conditions associated with target receptors, such as cancer, angiogenesis, or HIV infections.

250

A review of nanotechnological approaches for the prophylaxis of HIV/AIDS  

PubMed Central

Successful treatment and control of HIV/AIDS is one of the biggest challenges of 21st century. More than 33 million individuals are infected with HIV worldwide and more than 2 million new cases of HIV infection have been reported. The situation demands development of effective prevention strategies to control the pandemic of AIDS. Due to lack of availability of an effective HIV vaccine, antiretroviral drugs and nucleic acid therapeutics like siRNA have been explored for HIV prophylaxis. Clinical trials shave shown that antiretroviral drugs, tenofovir and emtricitabine can offer some degree of HIV prevention. However, complete prevention of HIV infection has not been achieved yet. Nanotechnology has brought a paradigm shift in the diagnosis, treatment and prevention of many diseases. The current review discusses potential of various nanocarriers such as dendrimers, polymeric nanoparticles, liposomes, lipid nanocarriers, drug nanocrystals, inorganic nanocarriers and nanofibers in improving efficacy of various modalities available for HIV prophylaxis. PMID:23726227

Date, Abhijit A.; Destache, Christopher J.

2013-01-01

251

CCR5 as a natural and modulated target for inhibition of HIV.  

PubMed

Human immunodeficiency virus type 1 (HIV-1) infection of target cells requires CD4 and a co-receptor, predominantly the chemokine receptor CCR5. CCR5-delta32 homozygosity results in a truncated protein providing natural protection against HIV infection-this without detrimental effects to the host-and transplantation of CCR5-delta32 stem cells in a patient with HIV ("Berlin patient") achieved viral eradication. As a more feasible approach gene-modification strategies are being developed to engineer cellular resistance to HIV using autologous cells. We have developed a dual therapeutic anti-HIV lentiviral vector (LVsh5/C46) that down-regulates CCR5 and inhibits HIV-1 fusion via cell surface expression of the gp41-derived peptide, C46. This construct, effective against multiple strains of both R5- and X4-tropic HIV-1, is being tested in Phase I/II trials by engineering HIV-resistant hematopoietic cells. PMID:24381033

Burke, Bryan P; Boyd, Maureen P; Impey, Helen; Breton, Louis R; Bartlett, Jeffrey S; Symonds, Geoff P; Hütter, Gero

2014-01-01

252

Evolution of HIV treatment guidelines in high and low-income countries: Converging recommendations  

PubMed Central

Over the past 15 years, antiretroviral treatment guidelines for HIV infection have evolved significantly, reflective of the major advances in this therapeutic area. Evidenced-based recommendations have largely replaced expert opinion, while diagnostic monitoring and therapeutic interventions have become more sophisticated and effective. Just ten years ago, there was a marked difference in access to antiretroviral therapy for patients in wealthy and impoverished countries. The increasing availability of therapy across the globe, however, has made it possible for international guidelines to more closely resemble those in industrialized countries. This article compares the evolution of antiretroviral therapy treatment guidelines from the United States Department of Health and Human Services and the World Health Organization, focusing on when to initiate ART in asymptomatic patients and in those with an opportunistic infection; initial regimens in general population and in special populations; when to change and what to change; and laboratory monitoring. PMID:24374148

Richardson, Eugene T.; Grant, Philip M.; Zolopa, Andrew R.

2014-01-01

253

FACT SHEETS HIV and Pregnancy  

E-print Network

FACT SHEETS HIV and Pregnancy HIV Testing and Pregnancy Mother-to-Child Transmission of HIV Anti-HIV Medications for Use in Pregnancy Safety of Anti-HIV Medications During Pregnancy Preventing Transmission and Pregnancy These fact sheets on HIV and pregnancy are intended for women infected with HIV who are pregnant

Levin, Judith G.

254

Antibody targeted drugs as cancer therapeutics  

Microsoft Academic Search

Treatment of cancer is a double-edged sword: it should be as aggressive as possible to completely destroy the tumour, but it is precisely this aggressiveness which often causes severe side effects — a reason why some promising therapeutics can not be applied systemically. In addition, therapeutics such as cytokines that physiologically function in a para- or autocrine fashion require a

David Schrama; Ralph A. Reisfeld; Jürgen C. Becker

2006-01-01

255

A Novel HIV-1 Entry Inhibitor  

Cancer.gov

Soluble forms (sCD4) of human CD4, the HIV-1 primary receptor, are potent HIV-1 entry inhibitors. Both four-domain (D1-4) and two-domain (D1D2) sCD4 and their fusion proteins have been tested as candidate therapeutics in animal models and in human clinical trials and were well tolerated by patients with no significant clinical or immunologic toxicities and exhibited significant inhibitory activities. However, their activities were transient and the virus rapidly rebound.

256

Stages of HIV Infection  

MedlinePLUS

... However, thereâ??s good news: when used consistently, antiretroviral therapy (ART) prevents the HIV virus from multiplying and from ... the time between HIV and AIDS: Taking antiretroviral therapy Staying in HIV ... noted above, when used consistently, ART prevents the HIV virus from multiplying and from ...

257

HIV Testing and Pregnancy  

MedlinePLUS

... woman infected with HIV to her baby during pregnancy, during labor and delivery, or by breastfeeding. HIV antibody test: an HIV test that checks for HIV antibodies in a person’s blood, urine, or fluids from the mouth. When the body ...

258

HIV Structural Database  

National Institute of Standards and Technology Data Gateway

SRD 102 HIV Structural Database (Web, free access)   The HIV Protease Structural Database is an archive of experimentally determined 3-D structures of Human Immunodeficiency Virus 1 (HIV-1), Human Immunodeficiency Virus 2 (HIV-2) and Simian Immunodeficiency Virus (SIV) Proteases and their complexes with inhibitors or products of substrate cleavage.

259

HIV inactivation in plasma products.  

PubMed

This is a review of therapeutic plasma products viz., coagulation factor concentrates, immunoglobulins, volume expanders, and protease inhibitors, and the progress made in rendering them free from transmitting infectious virus. Problems associated with the development of plasma products and the risks associated with their use are addressed. The recent technical advances designed to inactivate the hepatitis virus which led to the inactivation of HIV while preserving most of the biologic activity are reviewed. Today manufactured plasma products are essentially free from transmitting viral diseases of any significant clinical consequences. PMID:8226706

Mozen, M M

1993-01-01

260

Higher Homologous and Lower Cross-Reactive Gag-Specific T-Cell Responses in Human Immunodeficiency Virus Type 2 (HIV-2) Than in HIV-1 Infection?  

PubMed Central

Human immunodeficiency virus type 2 (HIV-2) infection results in slower CD4+ T-cell decline, lower plasma viral load levels, and hence slower progression of the disease than does HIV-1 infection. Although the reasons for this are not clear, it is possible that HIV-2 replication is more effectively controlled by host responses. We used aligned pools of overlapping HIV-1 and HIV-2 Gag peptides in an enhanced gamma interferon enzyme-linked immunospot assay to compare the levels of homologous and cross-reactive Gag-specific T-cell responses between HIV-1- and HIV-2-infected patients. HIV-2-infected patients showed broader and stronger homologous Gag-specific T-cell responses than HIV-1-infected patients. In contrast, the cross-reactive T-cell responses in HIV-2-infected patients were both narrower and weaker than those in HIV-1-infected patients, in line with overall weaker correlations between homologous and heterologous T-cell responses among HIV-2-infected patients than among HIV-1-infected patients. Cross-reactive responses in HIV-2-infected patients tended to correlate directly with HIV-1/HIV-2 Gag sequence similarities; this was not found in HIV-1-infected patients. The CD4+ T-cell counts of HIV-2-infected patients correlated directly with homologous responses and inversely with cross-reactive responses; this was not found in HIV-1-infected patients. Our data support a model whereby high-level HIV-2-specific T-cell responses control the replication of HIV-2, thus limiting viral diversification and priming of HIV-1 cross-reactive T-cell responses over time. However, we cannot exclude the possibility that HIV-2 replication is controlled by other host factors and that HIV-2-specific T-cell responses are better maintained in the context of slow viral divergence and a less damaged immune system. Understanding the nature of immune control of HIV-2 infection could be crucial for HIV vaccine design. PMID:18562522

Jennes, Wim; Camara, Makhtar; Dičye, Tandakha; Mboup, Souleymane; Kestens, Luc

2008-01-01

261

Oligonucleotide conjugates for therapeutic applications  

PubMed Central

Insufficient pharmacokinetic properties and poor cellular uptake are the main hurdles for successful therapeutic development of oligonucleotide agents. The covalent attachment of various ligands designed to influence the biodistribution and cellular uptake or for targeting specific tissues is an attractive possibility to advance therapeutic applications and to expand development options. In contrast to advanced formulations, which often consist of multiple reagents and are sensitive to a variety of preparation conditions, oligonucleotide conjugates are defined molecules, enabling structure-based analytics and quality control techniques. This review gives an overview of current developments of oligonucleotide conjugates for therapeutic applications. Attached ligands comprise peptides, proteins, carbohydrates, aptamers and small molecules, including cholesterol, tocopherol and folic acid. Important linkage types and conjugation methods are summarized. The distinct ligands directly influence biochemical parameters, uptake machanisms and pharmacokinetic properties. PMID:23883124

Winkler, Johannes

2013-01-01

262

The management of chronic prostatitis in men with HIV  

Microsoft Academic Search

Prostatitis is a common urologic diagnosis. Although treatment algorithms are available for this poorly understood entity,\\u000a several adaptations must be made in order to accommodate the therapeutic needs of HIV-positive patients. The most important\\u000a consideration when treating HIV-infected patients for prostatitis is their current immune status, whether they are immunocompromised\\u000a or not (non-progressive disease or reconstituted with highly active antiretroviral

Vincent M. Santillo; Franklin C. Lowe

2006-01-01

263

Influence of HIV and HCV on T cell antigen presentation and challenges in the development of vaccines.  

PubMed

Some of the central challenges for developing effective vaccines against HIV and hepatitis C virus (HCV) are similar. Both infections are caused by small, highly mutable, rapidly replicating RNA viruses with the ability to establish long-term chronic pathogenic infection in human hosts. HIV has caused 60 million infections globally and HCV 180 million and both viruses may co-exist among certain populations by virtue of common blood-borne, sexual, or vertical transmission. Persistence of both pathogens is achieved by evasion of intrinsic, innate, and adaptive immune defenses but with some distinct mechanisms reflecting their differences in evolutionary history, replication characteristics, cell tropism, and visibility to mucosal versus systemic and hepatic immune responses. A potent and durable antibody and T cell response is a likely requirement of future HIV and HCV vaccines. Perhaps the single biggest difference between the two vaccine design challenges is that in HCV, a natural model of protective immunity can be found in those who resolve acute infection spontaneously. Such spontaneous resolvers exhibit durable and functional CD4(+) and CD8(+) T cell responses (Diepolder et al., 1995; Cooper et al., 1999; Thimme et al., 2001; Grakoui et al., 2003; Lauer et al., 2004; Schulze Zur Wiesch et al., 2012). However, frequent re-infection suggests partial or lack of protective immunity against heterologous HCV strains, possibly indicative of the degree of genetic diversity of circulating HCV genotypes and subtypes. There is no natural model of protective immunity in HIV, however, studies of "elite controllers," or individuals who have durably suppressed levels of plasma HIV RNA without antiretroviral therapy, has provided the strongest evidence for CD8(+) T cell responses in controlling viremia and limiting reservoir burden in established infection. Here we compare and contrast the specific mechanisms of immune evasion used by HIV and HCV, which subvert adaptive human leukocyte antigen (HLA)-restricted T cell immunity in natural infection, and the challenges these pose for designing effective preventative or therapeutic vaccines. PMID:25352836

John, Mina; Gaudieri, Silvana

2014-01-01

264

The two human CXCR4 isoforms display different HIV receptor activities: consequences for the emergence of X4 strains.  

PubMed

CXCR4 is a chemokine receptor that plays key roles with its specific ligand, CXCL12, in stem cell homing and immune trafficking. It is also used as a coreceptor by some HIV-1 strains (X4 strains), whereas other strains (R5 strains) use an alternative coreceptor, CCR5. X4 strains mainly emerge at late stages of the infection and are linked to disease progression. Two isoforms of this coreceptor have been described in humans: CXCR4-A and CXCR4-B, corresponding to an unspliced and a spliced mRNA, respectively. In this study, we show that CXCR4-B, but not CXCR4-A, mediates an efficient HIV-1 X4 entry and productive infection. Yet, the chemotactic activity of CXCL12 on both isoforms was similar. Furthermore, HIV-R5 infection favored CXCR4-B expression over that of CXCR4-A. In vitro infection with an R5 strain increased CXCR4-B/CXCR4-A mRNA ratio in PBMCs, and this ratio correlated with HIV RNA plasma level in R5-infected individuals. In addition, the presence of the CXCR4-B isoform favored R5 to X4 switch more efficiently than did CXCR4-A in vitro. Hence, the predominance of CXCR4-B over CXCR4-A expression in PBMCs was linked to the ability of circulating HIV-1 strains to use CXCR4, as determined by genotyping. These data suggest that R5 to X4 switch could be favored by R5 infection-induced overexpression of CXCR4-B. Finally, we achieved a specific small interfering RNA-mediated knockdown of CXCR4-B. This represents a proof of concept for a possible gene-therapeutic approach aimed at blocking the HIV coreceptor activity of CXCR4 without knocking down its chemotactic activity. PMID:25230750

Duquenne, Charline; Psomas, Christina; Gimenez, Sandrine; Guigues, Adeline; Carles, Marie-Josée; Barbuat, Claudine; Lavigne, Jean-Philippe; Sotto, Albert; Reynes, Jacques; Guglielmi, Paul; Mettling, Clément; François, Vincent; Corbeau, Pierre

2014-10-15

265

Regulatory T Cells Expanded from Hiv-1-Infected Individuals Maintain Phenotype, Tcr Repertoire and Suppressive Capacity  

E-print Network

While modulation of regulatory T cell (Treg) function and adoptive Treg transfer are being explored as therapeutic modalities in the context of autoimmune diseases, transplantation and cancer, their role in HIV-1 pathogenesis ...

Angin, Mathieu

266

American Therapeutic Recreation Association  

MedlinePLUS

American Therapeutic Recreation Association Promoting Health & Wellness Services New Feature for Members Only ~ Network with Members Become a part ... Proposals for 2015 Annual Conference Join thousands of Therapeutic Recreation specialists today Join Now Renew your membership ...

267

In vivo emergence of HIV1 variants resistant to multiple protease inhibitors  

Microsoft Academic Search

INHIBITORS of the human immunodeficiency virus type 1 (HIV-1) protease have entered clinical study as potential therapeutic agents for HIV-1 infection. The clinical efficacy of HIV-1 reverse transcriptase inhibitors has been limited by the emergence of resistant viral variants. Similarly, variants expressing resistance to protease inhibitors have been derived in cell culture1-10. We now report the characterization of resistant variants

Jon H. Condra; William A. Schleif; Olga M. Blahy; Lori J. Gabryelski; Donald J. Graham; Julio Quintero; Audrey Rhodes; Helen L. Robbins; Elizabeth Roth; Malathi Shivaprakash; Donna Titus; Tao Yang; Hedy Tepplert; Kathleen E. Squires; Paul J. Deutsch; Emilio A. Emini

1995-01-01

268

Small molecule inactivation of HIV-1 NCp7 by repetitive intracellular acyl transfer  

PubMed Central

The zinc fingers of the HIV-1 nucleocapsid protein, NCp7, are prime targets for antiretroviral therapeutics. Here we show that S-acyl-2-mercaptobenzamide thioester (SAMT) chemotypes inhibit HIV by modifying the NCp7 region of Gag in infected cells, thereby blocking Gag processing and reducing infectivity. The thiol produced by SAMT reaction with NCp7 is acetylated by cellular enzymes to regenerate active SAMTs via a recycling mechanism unique among small molecule inhibitors of HIV. PMID:20953192

Jenkins, Lisa M. Miller; Ott, David E.; Hayashi, Ryo; Coren, Lori V.; Wang, Deyun; Xu, Qun; Schito, Marco L.; Inman, John K.; Appella, Daniel H.; Appella, Ettore

2010-01-01

269

A BLUEPRINT FOR HIV VACCINE DISCOVERY  

PubMed Central

Despite numerous attempts over many years to develop an HIV vaccine based on classical strategies, none has convincingly succeeded to date. A number of approaches are being pursued in the field, including building upon possible efficacy indicated by the recent RV144 clinical trial, which combined two HIV vaccines. Here, we argue for an approach based, in part, on understanding the HIV envelope spike and its interaction with broadly neutralizing antibodies (bnAbs) at the molecular level and using this understanding to design immunogens as possible vaccines. BnAbs can protect against virus challenge in animal models and many such antibodies have been isolated recently. We further propose that studies focused on how best to provide T cell help to B cells that produce bnAbs are crucial for optimal immunization strategies. The synthesis of rational immunogen design and immunization strategies, together with iterative improvements, offers great promise for advancing toward an HIV vaccine. PMID:23084910

Burton, Dennis R.; Ahmed, Rafi; Barouch, Dan H.; Butera, Salvatore T.; Crotty, Shane; Godzik, Adam; Kaufmann, Daniel E.; McElrath, M. Juliana; Nussenzweig, Michel C.; Pulendran, Bali; Scanlan, Chris N.; Schief, William R.; Silvestri, Guido; Streeck, Hendrik; Walker, Bruce D.; Walker, Laura M.; Ward, Andrew B.; Wilson, Ian A.; Wyatt, Richard

2012-01-01

270

Impact of Tat Genetic Variation on HIV-1 Disease  

PubMed Central

The human immunodeficiency virus type 1 (HIV-1) promoter or long-terminal repeat (LTR) regulates viral gene expression by interacting with multiple viral and host factors. The viral transactivator protein Tat plays an important role in transcriptional activation of HIV-1 gene expression. Functional domains of Tat and its interaction with transactivation response element RNA and cellular transcription factors have been examined. Genetic variation within tat of different HIV-1 subtypes has been shown to affect the interaction of the viral transactivator with cellular and/or viral proteins, influencing the overall level of transcriptional activation as well as its action as a neurotoxic protein. Consequently, the genetic variability within tat may impact the molecular architecture of functional domains of the Tat protein that may impact HIV pathogenesis and disease. Tat as a therapeutic target for anti-HIV drugs has also been discussed. PMID:22899925

Li, Luna; Dahiya, Satinder; Kortagere, Sandhya; Aiamkitsumrit, Benjamas; Cunningham, David; Pirrone, Vanessa; Nonnemacher, Michael R.; Wigdahl, Brian

2012-01-01

271

Interferon-? Is the Primary Plasma Type-I IFN in HIV-1 Infection and Correlates with Immune Activation and Disease Markers  

PubMed Central

Type-I interferon (IFN-I) has been increasingly implicated in HIV-1 pathogenesis. Various studies have shown elevated IFN-I and an IFN-I-induced gene and protein expression signature in HIV-1 infection, yet the elevated IFN-I species has not been conclusively identified, its source remains obscure and its role in driving HIV-1 pathogenesis is controversial. We assessed IFN-I species in plasma by ELISAs and bioassay, and we investigated potential sources of IFN-I in blood and lymph node tissue by qRT-PCR. Furthermore, we measured the effect of therapeutic administration of IFN? in HCV-infected subjects to model the effect of IFN? on chronic immune activation. IFN-I bioactivity was significantly increased in plasma of untreated HIV-1-infected subjects relative to uninfected subjects (p?=?0.012), and IFN? was the predominant IFN-I subtype correlating with IFN-I bioactivity (r?=?0.658, p<0.001). IFN? was not detectable in plasma of subjects receiving anti-retroviral therapy. Elevated expression of IFN? mRNA was limited to lymph node tissue cells, suggesting that peripheral blood leukocytes are not a major source of IFN? in untreated chronic HIV-1 infection. Plasma IFN-I levels correlated inversely with CD4 T cell count (p?=?0.003) and positively with levels of plasma HIV-1 RNA and CD38 expression on CD8 T cells (p?=?0.009). In hepatitis C virus-infected subjects, treatment with IFN-I and ribavirin increased expression of CD38 on CD8 T cells (p?=?0.003). These studies identify IFN? derived from lymph nodes, rather than blood leukocytes, as a possible source of the IFN-I signature that contributes to immune activation in HIV-1 infection. PMID:23437155

Hardy, Gareth A. D.; Sieg, Scott; Rodriguez, Benigno; Anthony, Donald; Asaad, Robert; Jiang, Wei; Mudd, Joseph; Schacker, Timothy; Funderburg, Nicholas T.; Pilch-Cooper, Heather A.; Debernardo, Robert; Rabin, Ronald L.; Lederman, Michael M.; Harding, Clifford V.

2013-01-01

272

HIV-1 Tat-induced microglial activation and neuronal damage is inhibited via CD45 modulation: A potential new treatment target for HAND  

PubMed Central

Microglia become activated in humans subsequent to infection with HIV, and uncontrolled brain inflammation plays a key role in neuronal injury and and cognitive dysfunction during HIV infection. Various studies have shown a deleterious role for the HIV regulatory protein Tat in the development and maintenance of HIV-associated neurocognitive disorders (HAND). One cell surface receptor implicated in inhibiting microglial activation is the protein-tyrosine phosphatase (PTP), CD45. It is especially effective at inhibiting microglial activation because its action takes place far upstream from proinflammatory intracellular signaling mediators. To investigate the possible role of CD45 in microglial responsiveness to HIV-1 Tat protein, we treated BV-2 microglia with a tyrosine phosphatase inhibitor [potassium bisperoxo (1, 10-phenanthroline) oxovanadate (phen), 5 ?M] and HIV-1 Tat protein (700ng/ml). We found a synergistic pro-inflammatory microglial activation as supported by tumor necrosis factor-alpha (TNF-?) and interleukin 1-beta (IL-1?) release, both of which were dependent on p44/42 mitogen-activated protein kinase (MAPK) activation. Stimulation of microglial CD45 by anti-CD45 antibody markedly inhibited these Tat or Tat/Phen effects via attenuation of p44/42 MAPK, suggesting CD45 negatively regulates microglial activation. As a validation of these findings in vivo, brains from transgenic mice deficient for CD45 through complete genetic ablation, or by CNS delivery of CD45shRNA, demonstrate markedly increased production of TNF-? 24 hours after intracerebroventricular injection of HIV-Tat protein (5?g/mouse) compared to control mice. This increased microglial activation was accompanied by astrogliosis and a significant loss of cortical neurons due to apoptosis in CD45 deficient animals. These results suggest therapeutic agents that activate CD45 PTP signaling may be effective in suppressing microglial activation associated with HAND. PMID:22937208

Jin, Jingji; Lam, Lucy; Sadic, Edin; Fernandez, Frank; Tan, Jun; Giunta, Brian

2012-01-01

273

FDA-Approved HIV Medicines  

MedlinePLUS

Treatment with HIV medicines is called antiretroviral therapy (ART). ART is recommended for everyone with HIV. People on ART take a combination of HIV medicines (called an HIV regimen) every day. A ...

274

HIV/AIDS Clinical Trials  

MedlinePLUS

... safe and effective in people. What is an HIV/AIDS clinical trial? HIV/AIDS clinical trials help ... related to HIV Can anyone participate in an HIV/AIDS clinical trial? It depends on the study. ...

275

Prevalence of mutations related to HIV1 antiretroviral resistance in Brazilian patients failing HAART  

Microsoft Academic Search

Background: Current guidelines for antiretroviral (ARV) therapy recommend at least triple-drug combination, the so-called highly active antiretroviral therapy (HAART). Not all patients respond to HAART and the development of drug resistance remains one of the most serious obstacles to sustained suppression of HIV. Objective: In an attempt to correlate the HIV therapeutic failure with reverse transcriptase (RT) and protease resistance

Amilcar Tanuri; Elena Caridea; Maria C. Dantas; Marisa G. Morgado; Daise L. C. Mello; Sandra Borges; Marisa Tavares; Selma B. Ferreira; Guilherme Santoro-Lopes; Claudia R. F. Martins; André L. C. Esteves; Ricardo S. Diaz; Sandra M. S. Andreo; Luiz A. P. Ferreira; Rodrigo Rodrigues; Tania Reuter; Ana M. S. Cavalcanti; Suelene M. de Oliveira; Heraclito B. de Barbosa; Paulo R. Teixeira; Pedro N. Chequer

2002-01-01

276

Resistance to HIV1 Infection: Lessons Learned from Studies of Highly Exposed Persistently Seronegative (HEPS) Individuals  

Microsoft Academic Search

The medical, social, and economic impact of the human immunodeficiency virus (HIV) epidemic has underscored the need to quickly develop effective control strategies. Vigorous efforts to develop a vaccine and therapeutic agents have not yet succeeded in containing the spread of the virus. Studies of persons who remain uninfected despite extensive exposure to HIV continue to provide valuable information on

Prasad S. Kulkarni; Salvatore T. Butera; Ann C. Duerr

2003-01-01

277

Celastrol Inhibits Tat-Mediated Human Immunodeficiency Virus (HIV) Transcription and Replication  

Microsoft Academic Search

Current drugs used for antiretroviral therapy against human immunodeficiency virus (HIV) have a narrow spectrum of activity and, more often, have associated toxicities and severe side effects in addition to developing resistance. Thus, there is a need to develop new therapeutic strategies against HIV\\/AIDS to complement the already existing ones. Surprisingly, transactivator of transcription (Tat), an early virus-encoded protein required

Vivek Narayan; Kodihalli C. Ravindra; Chris Chiaro; Daniele Cary; Bharat B. Aggarwal; Andrew J. Henderson; K. Sandeep Prabhu

2011-01-01

278

HIV infection en route to endogenization: two cases  

PubMed Central

The long-term spontaneous evolution of humans and the human immunodeficiency virus (HIV) is not well characterized; many vertebrate species, including humans, exhibit remnants of other retroviruses in their genomes that question such possible endogenization of HIV. We investigated two HIV-infected patients with no HIV-related disease and no detection with routine tests of plasma HIV RNA or cell-associated HIV DNA. We used Sanger and deep sequencing to retrieve HIV DNA sequences integrated in the human genome and tested the host humoral and cellular immune responses. We noticed that viruses from both patients were inactivated by the high prevalence of the transformation of tryptophan codons into stop codons (25% overall (3–100% per gene) and 24% overall (0–50% per gene)). In contrast, the humoral and/or cellular responses were strong for one patient and moderate for the other, indicating that a productive infection occurred at one stage of the infection. We speculate that the stimulation of APOBEC, the enzyme group that exchanges G for A in viral nucleic acids and is usually inhibited by the HIV protein Vif, has been amplified and made effective from the initial stage of the infection. Furthermore, we propose that a cure for HIV may occur through HIV endogenization in humans, as observed for many other retroviruses in mammals, rather than clearance of all traces of HIV from human cells, which defines viral eradication. PMID:25366539

Colson, P; Ravaux, I; Tamalet, C; Glazunova, O; Baptiste, E; Chabriere, E; Wiedemann, A; Lacabaratz, C; Chefrour, M; Picard, C; Stein, A; Levy, Y; Raoult, D

2014-01-01

279

HIV infection duration, social support and the level of trauma symptoms in a sample of HIV-positive Polish individuals.  

PubMed

The aim of this study was to investigate the relationship between the average HIV infection duration and the level of quantitatively rated post-traumatic stress disorder (PTSD) symptoms and social support dimensions in a sample of 562 Polish HIV+ adults. Possible moderating effects of social support on the relationship between the average HIV infection duration and the level of PTSD symptoms were also analysed. The results of this study suggest that the average HIV infection duration may intensify PTSD symptoms and deteriorate the perceived availability of social support in HIV+ individuals. However, a positive relationship between HIV infection duration and the level of trauma symptoms was observed only in the group of HIV+ individuals with low perceived available social support, but not in the group of HIV-infected individuals with high perceived available social support. This research provided some new insight into the psychological and social aspects of living with HIV. In particular, our results suggest that although HIV infection duration may intensify trauma symptoms and deteriorate social support, perceived available social support may act as a buffer against HIV-related trauma symptoms. PMID:25296635

Rzeszutek, Marcin; Oniszczenko, W?odzimierz; ?ebrowska, Magdalena; Firl?g-Burkacka, Ewa

2015-01-01

280

Allosteric Inhibitor Development Targeting HIV-1 Integrase  

PubMed Central

HIV-1 integrase (IN) is one of three essential enzymes for viral replication, and a focus of ardent antiretroviral drug discovery and development efforts. Diligent research has led to the development of the strand transfer specific chemical class of IN inhibitors, with two compounds from this group, raltegravir and elvitegravir, advancing the farthest in the US FDA approval process for any IN inhibitor discovered thus far. Raltegravir, developed by Merck & Co., has been US FDA approved for HIV-1 therapy, whereas elvitegravir, developed by Gilead Sciences and Japan Tobacco, has reached Phase III clinical trials. Although this is an undoubted success for the HIV-1 IN drug discovery field, the development of HIV-1 IN strand transfer specific drug resistant viral strains upon clinical use of the compounds is expected in the patient. Furthermore the problem of strand transfer specific IN drug resistance will be exacerbated by the development of cross-resistant viral strains due to an overlapping binding orientation at the IN active site and an equivalent inhibitory mechanism for the two compounds. This inevitability will result in no available IN-targeted therapeutic options for HIV-1 treatment experienced patients. The development of allosterically targeted IN inhibitors presents an extremely advantageous approach for the discovery of compounds effective against IN strand transfer drug resistant viral strains, and would likely show synergy with all available FDA approved antiretroviral HIV-1 therapeutics, including the IN strand transfer specific compounds. Here we review the concept of allosteric IN inhibition, and the small molecules that have been investigated to bind non-active site regions to inhibit IN function. PMID:21275045

Al-Mawsawi, Laith Q.; Neamati, Nouri

2011-01-01

281

Emerging trends in plasma-free manufacturing of recombinant protein therapeutics expressed in mammalian cells  

PubMed Central

Mammalian cells are the expression system of choice for therapeutic proteins, especially those requiring complex post-translational modifications. Traditionally, these cells are grown in medium supplemented with serum and other animal-or human-derived components to support viability and productivity. Such proteins are also typically added as excipients and stabilizers in the final drug formulation. However, the transmission of hepatitis B in the 1970s and of hepatitis C and HIV in the 1980s through plasma-derived factor VIII concentrates had catastrophic consequences for hemophilia patients. Thus, due to regulatory concerns about the inherent potential for transmission of infectious agents as well as the heterogeneity and lack of reliability of the serum supply, a trend has emerged to eliminate the use of plasma-derived additives in the production and formulation of recombinant protein therapeutics. This practice began with products used in the treatment of hemophilia and is progressively expanding throughout the entire industry. The plasma-free method of producing recombinant therapeutics is accomplished by the use of both cell culture media and final product formulations that do not contain animal-or human-derived additives. A number of recombinant therapeutic proteins for the treatment of several different diseases have been produced by plasma-free processes, with the objective of improving safety by eliminating blood-borne pathogens or by reducing immunogenicity. This review describes the factors that drove the development of plasma-free protein therapeutics and provides examples of advances in manufacturing that have made possible the removal of human and animal-derived products from all steps of recombinant protein production. PMID:19226552

Grillberger, Leopold; Kreil, Thomas R; Nasr, Sonia; Reiter, Manfred

2009-01-01

282

Toll gates: An emerging therapeutic target  

PubMed Central

Innate immune system forms the first line of defense against microbial infections, as it exerts an immediate response. Innate immunity works through Toll-like receptors (TLRs) which functions as primary sensors of pathogens. TLR activates multiple signaling cascades leading to the induction of genes responsible for the release of inflammatory cytokines and type I interferon. Thus, they induce antimicrobial responses and also have an instructive role in adaptive immunity. However, TLR-mediated inflammation is said to be responsible for many of the destructive host responses in inflammatory diseases like periodontitis. Hence, therapeutics targeting TLRs are being used to treat disease such as HIV, Hepatitis B, asthma etc. Recently, synthetic TLR agonists are tried as novel vaccine adjuvant in treating periodontal diseases. This paper reviews the scope of TLR-based therapeutics in treating periodontitis. PMID:25624622

Maheaswari, Rajendran; Sivasankar, Kiruthika; Subbarayan, Sathya

2014-01-01

283

[HIV prophylaxis kits. A concept for emergency treatment in the context of postexposure prophylaxis].  

PubMed

Occupational transmission of HIV among healthcare personnel is rare but has repeatedly been published in the literature. Early initiation of postexposure HIV prophylaxis (HIV-PEP) is crucial to prevent virus transmission. For this reason the need for HIV-PEP has to be evaluated immediately and if necessary, started as soon as possible. This article presents an early intervention program in a university hospital which enables healthcare personnel immediate 24/7/365 access to a HIV-PEP prophylaxis kit following occupational HIV exposure. PMID:24292193

Wicker, S; Walcher, F; Wutzler, S; Marzi, I; Stephan, C

2014-01-01

284

Interaction of the HIV-1 gp120 Viral Protein V3 Loop with Bacterial Lipopolysaccharide  

PubMed Central

HIV-1 represents an elusive target for therapeutic compounds due to its high rate of mutation. Targeting structural patterns instead of a constantly changing specific three-dimensional structure may represent an approach that is less sensitive to viral mutations. The V3 loop of gp120 of HIV-1, which is responsible for binding of viral gp120 to CCR5 or CXCR4 coreceptors, has already been identified as an effective target for the inhibition of viral entry. The peptide derived from the V3 loop of gp120 specifically interacts with the lipid A moiety of LPS, as does the full gp120 protein. NMR analysis of V3 in complex with LPS shows formation of an amphipathic turn. The interaction between LPS and V3 relies on the structural pattern, comprising a combination of hydrophobic and charge interactions, similar to the interaction between antimicrobial peptides and LPS. LPS inhibited binding of gp120 to the surface of target T cells. Nonendotoxic LPS antagonists inhibited viral infection, demonstrating the possibility for the development of an inhibitor of HIV-1 attachment to T cells based on the recognition of a conserved structural pattern. PMID:21636577

Majerle, Andreja; Pristovšek, Primož; Man?ek-Keber, Mateja; Jerala, Roman

2011-01-01

285

HIV-associated obstructive lung diseases: insights and implications for the clinician  

PubMed Central

The effectiveness of antiretroviral therapy to control HIV infection has led to the emergence of an older HIV population who are at risk of chronic diseases. Through a comprehensive search of major databases, this Review summarises information about the associations between chronic obstructive pulmonary disease (COPD), asthma, and HIV infection. Asthma and COPD are more prevalent in HIV-infected populations; 16–20% of individuals with HIV infection have asthma or COPD, and poorly controlled HIV infection worsens spirometric and diffusing capacity measurements, and accelerates lung function decline by about 55–75 mL/year. Up to 21% of HIV-infected individuals have obstructive ventilatory defects and reduced diffusing capacity is seen in more than 50% of HIV-infected populations. Specific pharmacotherapy considerations are needed to care for HIV-infected populations with asthma or COPD–protease inhibitor regimens to treat HIV (such as ritonavir) can result in systemic accumulation of inhaled corticosteroids and might increase pneumonia risk, exacerbating the toxicity of this therapy. Therefore, it is essential for clinicians to have a heightened awareness of the increased risk and manifestations of obstructive lung diseases in HIV-infected patients and specific therapeutic considerations to care for this population. Screening spirometry and tests of diffusing capacity might be beneficial in HIV-infected people with a history of smoking or respiratory symptoms. PMID:24831854

Drummond, M Bradley; Kirk, Gregory D

2014-01-01

286

HIV and Its Treatment Changing an HIV Treatment Regimen Changing an HIV Treatment Regimen  

E-print Network

HIV and Its Treatment ­ Changing an HIV Treatment Regimen Changing an HIV Treatment Regimen Will my HIV treatment regimen ever change? At some point, you may need to adjust or change your regimen an HIV treatment regimen? There are several reasons why a person may switch to another HIV regimen

Levin, Judith G.

287

Evolutionary origin on HIV zThe closest relatives of HIV-1 and HIV-2  

E-print Network

Evolutionary origin on HIV zThe closest relatives of HIV-1 and HIV-2 are simian immunodeficiency viruses (SIV). zThere is evidence for multiple transmissions from SIV into humans. zHIV-1 is very closely of virulence. #12;HIV is a quasispecies zViral replication is error prone. zHIV reverse transcriptase and RNA

Moehlis, Jeff

288

Canadian consensus statement on HIV and its transmission in the context of criminal law  

PubMed Central

INTRODUCTION: A poor appreciation of the science related to HIV contributes to an overly broad use of the criminal law against individuals living with HIV in cases of HIV nondisclosure. METHOD: To promote an evidence-informed application of the law in Canada, a team of six Canadian medical experts on HIV and transmission led the development of a consensus statement on HIV sexual transmission, HIV transmission associated with biting and spitting, and the natural history of HIV infection. The statement is based on a literature review of the most recent and relevant scientific evidence (current as of December 2013) regarding HIV and its transmission. It has been endorsed by >70 additional Canadian HIV experts and the Association of Medical Microbiology and Infectious Disease Canada. RESULTS: Scientific and medical evidence clearly indicate that HIV is difficult to transmit during sex. For the purpose of informing the justice system, the per-act possibility of HIV transmission through sex, biting or spitting is described along a continuum from low possibility, to negligible possibility, to no possibility of transmission. This possibility takes into account the impact of factors such as the type of sexual acts, condom use, antiretroviral therapy and viral load. Dramatic advances in HIV therapy have transformed HIV infection into a chronic manageable condition. DISCUSSION: HIV physicians and scientists have a professional and ethical responsibility to assist those in the criminal justice system to understand and interpret the science regarding HIV. This is critical to prevent miscarriage of justice and to remove unnecessary barriers to evidence-based HIV prevention strategies. PMID:25285108

Loutfy, Mona; Tyndall, Mark; Baril, Jean-Guy; Montaner, Julio SG; Kaul, Rupert; Hankins, Catherine

2014-01-01

289

School education and HIV control in sub-Saharan Africa: from discord to harmony?  

Microsoft Academic Search

HIV is widely regarded as a disease of poverty and ignorance. However, within sub-Saharan Africa, more developed countries and sub-populations appear to have higher levels of HIV prevalence. This paper considers the evidence and possible reasons for this, by focusing on the relationships between education and the spread of HIV at the macro and micro levels. It is concluded that

Simon Gregson; Heather Waddell; Stephen Chandiwana

2001-01-01

290

HIV-1 Prevention for HIV-1 Serodiscordant Couples  

PubMed Central

A substantial proportion of HIV-1-infected individuals in sub-Saharan Africa are in stable relationships with HIV-1-uninfected partners, and HIV-1 serodiscordant couples thus represent an important target population for HIV-1 prevention. Couple-based HIV-1 testing and counseling facilitates identification of HIV-1 serodiscordant couples, counseling about risk reduction, and referrals to HIV-1 treatment, reproductive health services, and support services. Maximizing HIV-1 prevention for HIV-1 serodiscordant couples requires a combination of strategies, including counseling about condoms, sexual risk, fertility, contraception, and the clinical and prevention benefits of antiretroviral therapy (ART) for the HIV-1-infected partner; provision of clinical care and ART for the HIV-1-infected partner; antenatal care and services to prevent mother to child transmission for HIV-1- infected pregnant women; male circumcision for HIV-1-uninfected men; and, pending guidelines and demonstration projects, oral pre-exposure prophylaxis (PrEP) for HIV-1-uninfected partners. PMID:22415473

Curran, Kathryn; Baeten, Jared M.; Coates, Thomas J.; Kurth, Ann; Mugo, Nelly R.

2013-01-01

291

Iron chelators ICL670 and 311 inhibit HIV-1 transcription  

SciTech Connect

HIV-1 replication is induced by an excess of iron and iron chelation by desferrioxamine (DFO) inhibits viral replication by reducing proliferation of infected cells. Treatment of cells with DFO and 2-hydroxy-1-naphthylaldehyde isonicotinoyl hydrazone (311) inhibit expression of proteins that regulate cell-cycle progression, including cycle-dependent kinase 2 (CDK2). Our recent studies showed that CDK2 participates in HIV-1 transcription and viral replication suggesting that inhibition of CDK2 by iron chelators might also affect HIV-1 transcription. Here we evaluated the effect of a clinically approved orally effective iron chelator, 4-[3,5-bis-(hydroxyphenyl)-1,2,4-triazol-1-yl]-benzoic acid (ICL670) and 311 on HIV-1 transcription. Both ICL670 and 311 inhibited Tat-induced HIV-1 transcription in CEM-T cells, 293T and HeLa cells. Neither ICL670 nor 311 induced cytotoxicity at concentrations that inhibited HIV-1 transcription. The chelators decreased cellular activity of CDK2 and reduced HIV-1 Tat phosphorylation by CDK2. Neither ICL670A or 311 decreased CDK9 protein level but significantly reduced association of CDK9 with cyclin T1 and reduced phosphorylation of Ser-2 residues of RNA polymerase II C-terminal domain. In conclusion, our findings add to the evidence that iron chelators can inhibit HIV-1 transcription by deregulating CDK2 and CDK9. Further consideration should be given to the development of iron chelators for future anti-retroviral therapeutics.

Debebe, Zufan; Ammosova, Tatyana [Center for Sickle Cell Disease, Howard University College of Medicine, 520 W. St., N.W., Washington, DC 20060 (United States); Jerebtsova, Marina [Children's National Medical Center, CRI Center for Cancer and Immunology, 111 Michigan Ave., N.W., Washington, DC 20060 (United States); Kurantsin-Mills, Joseph [Department of Biophysics and Physiology, Howard University College of Medicine, 520 W. St., N.W., Washington, DC 20060 (United States); Niu, Xiaomei; Charles, Sharroya [Center for Sickle Cell Disease, Howard University College of Medicine, 520 W. St., N.W., Washington, DC 20060 (United States); Richardson, Des R. [Iron Metabolism and Chelation Program, Department of Pathology, Blackburn Building (D06), University of Sydney, Sydney, New South Wales, 2006 Australia (Australia); Ray, Patricio E. [Children's National Medical Center, CRI Center for Cancer and Immunology, 111 Michigan Ave., N.W., Washington, DC 20060 (United States); Gordeuk, Victor R. [Center for Sickle Cell Disease, Howard University College of Medicine, 520 W. St., N.W., Washington, DC 20060 (United States); Nekhai, Sergei [Center for Sickle Cell Disease, Howard University College of Medicine, 520 W. St., N.W., Washington, DC 20060 (United States); Department of Biochemistry and Molecular Biology, Howard University College of Medicine, 520 W. St., N.W., Washington, DC 20060 (United States)], E-mail: snekhai@howard.edu

2007-10-25

292

Therapeutic depletion of natural killer cells controls persistent infection.  

PubMed

Persistent viral infections are associated with host and viral factors that impair effective antiviral immunity. Natural killer (NK) cells contribute to establishment of persistent lymphocytic choriomeningitis virus (LCMV) infection in mice through suppression of virus-specific T cell responses during the first few days of infection, but NK cell depletion during those early time points can enable severe T cell-mediated immune pathology and death of the host. Here we show that long after their peak in cytolytic activation, NK cells continue to support viral persistence at later times of infection. Delayed depletion of NK cells, 2 to 3 weeks after infection, enhanced virus-specific T cell responses and viral control. This enhancing effect of delayed NK cell depletion on antiviral immunity, in contrast to early NK cell depletion, was not associated with increased morbidity and mortality, and mice quickly regained weight after treatment. The efficacy of the depletion depended in part upon the size of the original virus inoculum, the viral load at the time of depletion, and the presence of CD4 T cells. Each of these factors is an important contributor to the degree of CD8 T cell dysfunction during viral persistence. Thus, NK cells may continuously contribute to exhaustion of virus-specific T cells during chronic infection, possibly by depleting CD4 T cells. Targeting of NK cells could thus be considered in combination with blockade of other immunosuppressive pathways, such as the interleukin-10 (IL-10) and programmed death 1 (PD-1) pathways, as a therapy to cure chronic human infections, including those with HIV or hepatitis C virus. IMPORTANCE Persistent virus infections are a major threat to global human health. The capacity of viruses, including HIV and hepatitis C virus, to overwhelm or subvert host immune responses contributes to a prolonged state of dampened antiviral immune functionality, which in turn facilitates viral persistence. Recent efforts have focused on therapeutics that can restore the effector functions of these functionally exhausted virus-specific T cells in order to expedite viral clearance. Here we establish that natural killer (NK) cells actively contribute to immune dysfunction and viral persistence at later stages of infection. This previously undescribed mechanism of immune suppression during chronic infection provides a vital clue for the design of novel therapeutic strategies targeting NK cell immunosuppressive activity in order to restore immune function and enhance viral control in chronically infected individuals. PMID:24284324

Waggoner, Stephen N; Daniels, Keith A; Welsh, Raymond M

2014-02-01

293

Establishing Restricted Expression of Caveolin-1 in HIV Infected Cells and Inhibition of Virus Replication  

PubMed Central

Background: Caveolin-1 (Cav-1) is the major protein of the caveolae and plays a role in multiple cellular functions and implicated to have anti-HIV activity. Regulated expression of Cav-1 is important for safe and effective use in order to exploit Cav-1 for HIV therapeutic applications. Methods: A series of Cav-1 and GFP expression vectors were constructed under the control of the HIV LTR for conditional expression or CMV promoter and the expression of Cav-1 was monitored in the presence or absence of Tat or HIV infection in order to establish the restricted expression of Cav-1 to HIV infected cells. Results: Cav-1 expression was evident under the control of the HIV LTR in the absence of Tat or HIV infection as demonstrated by immunoblot. Placing two internal ribosomal entry sequences (IRES) and a Rev response element, RRE (5’~ LTR-IRES-GFP-RRE-IRES-Cav-1~3’) resulted in no expression of Cav-1 in the absence of Tat with effective expression in the presence of Tat. Transduction of HIV permissive cells with this construct using a foamy virus vector show that Cav-1 was able to inhibit HIV replication by 82%. Cells that received LTR-IRES-GFP-RRE-IRES-Cav-1 remain healthy in the absence of Tat or HIV infection. Conclusion: These results taken together reveal the inclusion of two IRES establishes a significant reduction of leak through expression of Cav-1 in the absence of Tat or HIV infection. Such regulated expression will have therapeutic application of Cav-1 for HIV infection as well as broad applications which can be beneficial for other host-targeted interventions as therapeutics. PMID:25408776

Lo, Yung-Tsun; Nadeau, Peter E; Lin, Shanshan; Mergia, Ayalew

2014-01-01

294

Children and HIV  

MedlinePLUS

... Sheets Permission to Use Fact Sheets Sponsors and Advertising Privacy Policy Project Staff Contact ... a Language: Fact Sheet 612 Children and HIV HOW SERIOUS IS HIV FOR CHILDREN? HOW ARE CHILDREN ...

295

Treatment of HIV Infection  

MedlinePLUS

... information on enabling JavaScript. HIV/AIDS Skip Content Marketing Share this: Main Content Area Treatment of HIV ... and how it causes disease, thereby unlocking new targets for drug development. Promising medicines are then tested ...

296

HIV-AIDS Connection  

MedlinePLUS

... to develop. However, with time, a near-perfect correlation has been found between infection with HIV and ... Recently developed sensitive tests have shown a strong correlation between the amount of HIV in the blood ...

297

HIV and Immunizations  

MedlinePLUS

... a disease outbreak. Is there a vaccine against HIV? Testing is underway on experimental vaccines to prevent ... can benefit from vaccines against other diseases. Can HIV infection affect the safety and effectiveness of vaccines? ...

298

Smoking and HIV  

MedlinePLUS

... 28, 2014 Select a Language: Fact Sheet 803 Smoking and HIV WHY IS SMOKING MORE DANGEROUS FOR ... It can also worsen liver problems like hepatitis. Smoking and Side Effects People with HIV who smoke ...

299

HIV Life Cycle  

MedlinePLUS

... protecting the body from infection. HIV uses the machinery of the CD4 cells to multiply (make copies ... protecting the body from infection. HIV uses the machinery of the CD4 cells to multiply (make copies ...

300

HIV and Kidney Disease  

MedlinePLUS

... Select a Language: Fact Sheet 651 HIV and Kidney Disease WHY SHOULD PEOPLE WITH HIV CARE ABOUT KIDNEY ... disease. Kidney problems can lead to end-stage renal disease (ESRD) or kidney failure. This can require dialysis ...

301

HIV in Correctional Settings  

MedlinePLUS

... treatment. Learn more about this initiative . CDC supported Project START, an HIV, STI, and hepatitis prevention program for ... other HIV prevention programs. CDC continues to support Project START by providing resources, training, and capacity building to ...

302

Paying for HIV Care  

MedlinePLUS

... and Co-Payment Programs (Copyright © AIDS Treatment Data Network) - This online resource offers information on government and drug company-sponsored programs that help pay for HIV medicines. Social Security for People Living With HIV/AIDS - If you ...

303

A Case-Controlled Study of Successful Aging in Older Adults with HIV  

PubMed Central

OBJECTIVES There is a growing public health interest in the aging HIV-infected (HIV+) population, although there is a dearth of research on successful aging with HIV. This study aimed to understand the risk and protective factors associated with self-rated successful aging (SRSA) with HIV. DESIGN Cross-sectional, case-controlled. SETTING HIV Neurobehavioral Research Program and the Stein Institute for Research on Aging at University of California, San Diego. PARTICIPANTS Eighty-three community-dwelling HIV+ and 83 demographically matched HIV-uninfected (HIV?) individuals, enrolled between 12/1/11 and 5/10/12, mean age of 59 years, primarily Caucasian males, 69% with AIDS, who had been living with an HIV diagnosis for 16 years. Diagnostic criteria for HIV/AIDS was obtained through a blood draw. MEASUREMENTS Participants provided ratings of SRSA as part of a comprehensive survey which included measures of physical and emotional functioning and positive psychological traits. Relationships between how the different variables related to SRSA were explored. RESULTS While SRSA was lower in the HIV+ individuals than their HIV? counterparts, 66% of adults with HIV reported scores of 5 or higher on a 10-point scale of SRSA. Despite worse physical and mental functioning and greater psychosocial stress among the HIV+ participants, the two groups had comparable levels of optimism, personal mastery, and social support. SRSA in HIV+ individuals was associated with better physical and emotional functioning and positive psychological factors, but not HIV disease status or negative life events. CONCLUSION Successful psychosocial aging is possible in older HIV+ individuals. Positive psychological traits such as resilience, optimism, and sense of personal mastery have stronger relationship with SRSA than duration or severity of HIV disease. Research on interventions to enhance these positive traits in HIV+ adults is warranted. PMID:23759460

Moore, Raeanne C.; Moore, David J.; Thompson, Wesley; Vahia, Ipsit V.; Grant, Igor; Jeste, Dilip V.

2013-01-01

304

[Sanitary safety of GMOs used in therapeutics].  

PubMed

The recent progress in human therapeutics has been made possible thanks to molecular biology and its use in producing proteins having the same sequence and structure as that of human proteins. The use of GMOs allows production of proteins with high added value in therapeutics, which are of satisfactory quality. GMOs may also be directly administered to patients as gene therapy vectors. However, the use of GMOs in therapeutics must take into consideration some risks, particularly those of microbiological contamination, of neo-antigenicity as well as environmental risks with regard to the way of use of the GMO. Nevertheless, those risks are taken in due consideration in the development of those new medicinal products; solutions have been found to allow their use in therapeutics with a very positive benefit/risk ratio. Medicinal products from biotechnology have permitted considerable therapeutic progress without compromising health security. PMID:12669359

Trouvin, Jean-Hugues

2002-01-01

305

[Health security--GMOs in therapeutics].  

PubMed

The recent progress in human therapeutics has been made possible thanks to molecular biology and its use in producing proteins having the same sequence and structure as that of human proteins. The use of GMOs allows production of proteins with high added value in therapeutics, which are of satisfactory quality. GMOs may also be directly administered to patients as gene therapy vectors. However, the use of GMOs in therapeutics must take into consideration some risks, particularly those of microbiological contamination, of neo-antigenicity as well as environmental risks with regard to the way of use of the GMO. Nevertheless, those risks are taken in due consideration in the development of these new medicinal products; solutions have been found to allow their use in therapeutics with a very positive benefit/risk ratio. Medicinal products from biotechnology have enabled considerable therapeutic progress without compromising health security. PMID:12668948

Trouvin, J-H

2003-03-01

306

Selective elimination of HIV-1-infected cells by Env-directed, HIV-1-based virus-like particles  

SciTech Connect

We recently showed that both replicating and resting cells cultivated with ganciclovir (GCV) were killed when challenged with vesicular stomatitis virus G glycoprotein pseudotyped HIV-1-based virus-like particles (VLPs) carrying the Nef7 (i.e., an HIV-1 Nef mutant incorporating in virions at high levels)/herpes simplex virus-1 thymidine kinase (HSV-TK) fusion product. On this basis, a novel anti-HIV therapeutic approach based on Nef7/TK VLPs expressing X4 or R5 HIV cell receptor complexes has been attempted. We here report that (CD4-CXCR4) and (CD4-CCR5) Nef7-based VLPs efficiently enter cells infected by X4- or R5-tropic HIV-1 strains, respectively. Importantly, the delivery of the VLP-associated Nef7/TK led to cell death upon GCV treatment. Of interest, VLPs were effective also against non-replicating, HIV-1-infected primary human monocyte-derived macrophages. HIV-targeted VLPs represent a promising candidate for the treatment of persistently HIV-1-infected cells that are part of virus reservoirs resistant to HAART therapies.

Peretti, Silvia [AIDS Center, Istituto Superiore di Sanita, Viale Regina Elena, 299, 00161, Rome (Italy); Schiavoni, Ilaria [AIDS Center, Istituto Superiore di Sanita, Viale Regina Elena, 299, 00161, Rome (Italy); Pugliese, Katherina [AIDS Center, Istituto Superiore di Sanita, Viale Regina Elena, 299, 00161, Rome (Italy); Federico, Maurizio [AIDS Center, Istituto Superiore di Sanita, Viale Regina Elena, 299, 00161, Rome (Italy)]. E-mail: federico@iss.it

2006-02-05

307

Molecular Understanding of HIV-1 Latency  

PubMed Central

The introduction of highly active antiretroviral therapy (HAART) has been an important breakthrough in the treatment of HIV-1 infection and has also a powerful tool to upset the equilibrium of viral production and HIV-1 pathogenesis. Despite the advent of potent combinations of this therapy, the long-lived HIV-1 reservoirs like cells from monocyte-macrophage lineage and resting memory CD4+ T cells which are established early during primary infection constitute a major obstacle to virus eradication. Further HAART interruption leads to immediate rebound viremia from latent reservoirs. This paper focuses on the essentials of the molecular mechanisms for the establishment of HIV-1 latency with special concern to present and future possible treatment strategies to completely purge and target viral persistence in the reservoirs. PMID:22548060

Abbas, W.; Herbein, G.

2012-01-01

308

High-Affinity Recognition of HIV-1 Frameshift-Stimulating RNA Alters Frameshifting in Vitro and Interferes with HIV-1 Infectivity  

PubMed Central

The life cycle of the human immunodeficiency virus type 1 (HIV-1) has an absolute requirement for ribosomal frameshifting during protein translation in order to produce the polyprotein precursor of the viral enzymes. While an RNA stem-loop structure (the “HIV-1 Frameshift Stimulating Signal”, or HIV-1 FSS) controls the frameshift efficiency and has been hypothesized as an attractive therapeutic target, developing compounds that selectively bind this RNA and interfere with HIV-1 replication has proven challenging. Building on our prior discovery of a “hit” molecule able to bind this stem-loop, we now report the development of compounds displaying high affinity for the HIV-1 FSS. These compounds are able to enhance frameshifting more than 50% in a dual-luciferase assay in human embryonic kidney cells, and they strongly inhibit the infectivity of pseudotyped HIV-1 virions. PMID:24387306

2015-01-01

309

Distribution of HIV genomic DNA in brains of AIDS patients  

Microsoft Academic Search

Background: Data concerning the distribution of HIV in the brains of AIDS patients at different stages of viral infection might contribute towards: (1) understanding the route(s) of HIV entry into the brain and virus dissemination within the brain and (2) establishing a possible correlation between the extent of CNS damage and the distribution of virus in AIDS brains.Objective: To determine

Larry E. Bockstahler; Thomas Werner; Herber Festl; Serge Weis; Karl Max Einhaeup; Volker Erfle; Ruth Brack-Werner

1995-01-01

310

Mathematical Analysis of HIV1 Dynamics in Vivo  

Microsoft Academic Search

Mathematical models have proven valuable in understanding the dynamics of HIV-1 in- fection in vivo. By comparing these models to data obtained from patients undergoing antiretroviral drug therapy, it has been possible to determine many quantitative features of the interaction between HIV-1, the virus that causes AIDS, and the cells that are infected by the virus. The most dramatic nding

Alan S. Perelson; Patrick W. Nelson

311

Perceived Risk Modifies the Effect of HIV Knowledge on Sexual Risk Behaviors  

PubMed Central

Background: There is a large controversy in the literature about the inter-relations between perceived risk, knowledge, and risk behavior in different settings, and people at HIV risk are not an exception. Aim: To assess additive and multiplicative effect of perceived HIV risk and HIV knowledge on sexual risk behavior of Injecting Drug Users (IDUs). Method: We enrolled 162 street based IDUs to this analysis. Data came from a national survey of IDUs in Iran, with a cross sectional design. Socio-demographics (employment, education, marital status), HIV knowledge, perceived HIV risk, and four different sexual risk behavior were registered. In the first step, using spearman test, the association of HIV knowledge and risk behavior were tested, then possible moderating effect of perceived HIV risk on this association was determined. Results: Although among IDUs with low perceived HIV risk, HIV knowledge was negatively associated with sexual risk behavior (P?HIV risk (P?>?0.05 for all). Thus perceived HIV risk moderated the association between HIV knowledge and sexual risk behavior. Conclusion: Perceived risk should be taken into consideration when studying the effect of HIV knowledge on sexual risk behavior of IDUs. Findings may help us better understand negative effects of fear arousing interventions as a part of HIV prevention media campaigns. PMID:24350202

Noroozinejad, Gholamhossein; Yarmohmmadi Vasel, Mosaieb; Bazrafkan, Fatemeh; Sehat, Mahmoud; Rezazadeh, Majid; Ahmadi, Khodabakhsh

2013-01-01

312

National HIV Testing Day —  

E-print Network

of testing in detecting, treating, and preventing human immunodeficiency virus (HIV) infection. HIV testing is the essential entry point to a continuum of prevention, healthcare, and social services that improve the quality of life and the length of survival for persons with HIV (1). Persons with HIV who receive appropriate treatment, monitoring, and health care also reduce their chances of transmitting HIV to others. CDC recommends that all persons aged 13–64 years be screened for HIV in health-care settings located in areas where the prevalence of undiagnosed HIV infection is>0.1%, and that persons with increased risk for HIV be retested at least annually (2). In April 2013, the U.S. Preventive Services Task Force updated its 2005 guidelines on HIV screening, to recommend that clinicians screen all persons aged 15–65 years for HIV infection at least once, regardless of their risk; that younger adolescents and older adults with increased risk also be screened; and that persons with increased risk be screened more frequently (3). These updated recommendations are based on increasing evidence of the benefits of early antiretroviral therapy for HIV-infected persons and its effectiveness in preventing HIV transmission. Additional information is available at

unknown authors

2013-01-01

313

HIV and adolescents  

Microsoft Academic Search

Seroprevalence studies and documented sex and drug use risk behaviors indicate the importance of primary prevention programs for HIV among adolescents. Females and minority adolescents are at particular risk. Prevention workers must decide which strategies to advocate: abstinence, monogamy, HIV testing, screening partners, or explicit instruction of safer acts. Youths must be helped to personalize knowledge of HIV, acquire coping

Mary Jane Rotheram-Borus; Cheryl Koopman

1991-01-01

314

HIV Antibody Test  

MedlinePLUS

... next test to perform is a HIV-1 RNA test (nucleic acid amplification test, NAAT). If the HIV-1 RNA is positive, then the test is considered positive. ^ ... HIV-2 differentiation test and a DNA or RNA-based nucleic acid amplification test in persons with ...

315

HIV serosurveillance of newborns  

Microsoft Academic Search

This article reviews the complex issues surrounding the anonymous HIV testing of newborns to monitor the prevalence of HIV infection in women of childbearing age. This serosurveillance of newborns has become a topic of legislative debate focusing on disclosure of currently anonymous results of HIV antibody tests of newborns, thus revealing the serostatus of the mother. This, in effect, would

Carol Garrett

1995-01-01

316

Neutralizing the HIV reservoir.  

PubMed

Halper-Stromberg et al. use a humanized mouse model to demonstrate that broadly neutralizing antibodies, when administered with a combination of HIV latency activators, can reduce persistent HIV reservoirs, as measured by plasma virus rebound. Their results support the use of broadly neutralizing antibodies in HIV-reservoir-purging strategies. PMID:25171398

Marsden, Matthew D; Zack, Jerome A

2014-08-28

317

Peptide and protein-based inhibitors of HIV-1 co-receptors  

PubMed Central

Human immunodeficiency virus (HIV) afflicts an estimated 30 million people globally, making it a continuing pandemic. Despite major research efforts, the rate of new infections has remained relatively static over time. This article reviews an emerging strategy for the treatment of HIV, the inhibition of the co-receptors necessary for HIV entry, CCR5 and CXCR4. The aim of this article is to highlight potential therapeutics derived from peptides and proteins that show particular promise in HIV treatment. Molecules that act on CCR5, CXCR4 or on both receptors will be discussed herein. PMID:23856897

von Recum, Horst A; Pokorski, Jonathan K

2014-01-01

318

Ribotoxin restrictocin manifests anti-HIV-1 activity through its specific ribonuclease activity.  

PubMed

Restrictocin, a highly specific ribonuclease produced by Aspergillus restrictus, cleaves a single phosphodiester bond in a universally conserved stem and loop structure termed sarcin/ricin loop within the large ribosomal RNA of all organisms. In the current study, we demonstrate restrictocin to manifest anti-HIV-1 activity in two model cell systems. Using two mutants of restrictocin, we further show that the anti-HIV-1 activity of restrictocin is due to its specific ribonucleolytic activity. The study suggests that restrictocin is able to recognize region(s) within HIV-1 genome as its target. Restrictocin appears to have potential as a therapeutic antiviral agent against HIV-1. PMID:25709025

Yadav, Santosh K; Batra, Janendra K

2015-05-01

319

Dendritic cells exposed to MVA-based HIV-1 vaccine induce highly functional HIV-1-specific CD8(+) T cell responses in HIV-1-infected individuals.  

PubMed

Currently, MVA virus vectors carrying HIV-1 genes are being developed as HIV-1/AIDS prophylactic/therapeutic vaccines. Nevertheless, little is known about the impact of these vectors on human dendritic cells (DC) and their capacity to present HIV-1 antigens to human HIV-specific T cells. This study aimed to characterize the interaction of MVA and MVA expressing the HIV-1 genes Env-Gag-Pol-Nef of clade B (referred to as MVA-B) in human monocyte-derived dendritic cells (MDDC) and the subsequent processes of HIV-1 antigen presentation and activation of memory HIV-1-specific T lymphocytes. For these purposes, we performed ex vivo assays with MDDC and autologous lymphocytes from asymptomatic HIV-infected patients. Infection of MDDC with MVA-B or MVA, at the optimal dose of 0.3 PFU/MDDC, induced by itself a moderate degree of maturation of MDDC, involving secretion of cytokines and chemokines (IL1-ra, IL-7, TNF-?, IL-6, IL-12, IL-15, IL-8, MCP-1, MIP-1?, MIP-1?, RANTES, IP-10, MIG, and IFN-?). MDDC infected with MVA or MVA-B and following a period of 48 h or 72 h of maturation were able to migrate toward CCL19 or CCL21 chemokine gradients. MVA-B infection induced apoptosis of the infected cells and the resulting apoptotic bodies were engulfed by the uninfected MDDC, which cross-presented HIV-1 antigens to autologous CD8(+) T lymphocytes. MVA-B-infected MDDC co-cultured with autologous T lymphocytes induced a highly functional HIV-specific CD8(+) T cell response including proliferation, secretion of IFN-?, IL-2, TNF-?, MIP-1?, MIP-1?, RANTES and IL-6, and strong cytotoxic activity against autologous HIV-1-infected CD4(+) T lymphocytes. These results evidence the adjuvant role of the vector itself (MVA) and support the clinical development of prophylactic and therapeutic anti-HIV vaccines based on MVA-B. PMID:21625608

Climent, Núria; Guerra, Susana; García, Felipe; Rovira, Cristina; Miralles, Laia; Gómez, Carmen Elena; Piqué, Núria; Gil, Cristina; Gatell, José María; Esteban, Mariano; Gallart, Teresa

2011-01-01

320

Streamlining HIV testing for HIV preexposure prophylaxis.  

PubMed

HIV-testing algorithms for preexposure prophylaxis (PrEP) should be optimized to minimize the risk of drug resistance, the time off PrEP required to evaluate false-positive screening results, and costs and to expedite the start of therapy for those confirmed to be infected. HIV rapid tests (RTs) for anti-HIV antibodies provide results in less than 1 h and can be conducted by nonlicensed staff at the point of care. In many regions, Western blot (WB) testing is required to confirm reactive RT results. WB testing, however, causes delays in diagnosis and adds expense. The iPrEx study evaluated the safety and efficacy of daily oral emtricitabine-tenofovir disoproxil fumarate among HIV-seronegative men and transgender women who have sex with men: HIV infection was assessed with two RTs plus WB confirmation, followed by HIV-1 plasma viral load testing. During the iPrEx study, there were 51,260 HIV status evaluations among 2,499 volunteers using RTs: 142 (0.28%) had concordant positive results (100% were eventually confirmed) and 19 (0.04%) had discordant results among 14 participants; 11 were eventually determined to be HIV infected. A streamlined approach using only one RT to screen and a second RT to confirm (without WB) would have had nearly the same accuracy. Discrepant RT results are best evaluated with nucleic acid testing, which would also increase sensitivity. PMID:25378570

Guanira, Juan V; Leigler, Teri; Kallas, Esper; Schechter, Mauro; Sharma, Usha; Glidden, David; Grant, Robert M

2015-01-01

321

Vorinostat positively regulates synaptic plasticity genes expression and spine density in HIV infected neurons: role of nicotine in progression of HIV-associated neurocognitive disorder  

PubMed Central

Background HIV-associated neurocognitive disorder (HAND) is characterized by development of cognitive, behavioral and motor abnormalities, and occurs in approximately 50% of HIV infected individuals. In the United States, the prevalence of cigarette smoking ranges from 35-70% in HIV-infected individuals compared to 20% in general population. Cognitive impairment in heavy cigarette smokers has been well reported. However, the synergistic effects of nicotine and HIV infection and the underlying mechanisms in the development of HAND are unknown. Results In this study, we explored the role of nicotine in the progression of HAND using SK-N-MC, a neuronal cell line. SK-N-MC cells were infected with HIV-1 in the presence or absence of nicotine for 7 days. We observed significant increase in HIV infectivity in SK-N-MC treated with nicotine compared to untreated HIV-infected neuronal cells. HIV and nicotine synergize to significantly dysregulate the expression of synaptic plasticity genes and spine density; with a concomitant increase of HDAC2 levels in SK-N-MC cells. In addition, inhibition of HDAC2 up-regulation with the use of vorinostat resulted in HIV latency breakdown and recovery of synaptic plasticity genes expression and spine density in nicotine/HIV alone and in co-treated SK-N-MC cells. Furthermore, increased eIF2 alpha phosphorylation, which negatively regulates eukaryotic translational process, was observed in HIV alone and in co-treatment with nicotine compared to untreated control and nicotine alone treated SK-N-MC cells. Conclusions These results suggest that nicotine and HIV synergize to negatively regulate the synaptic plasticity gene expression and spine density and this may contribute to the increased risk of HAND in HIV infected smokers. Apart from disrupting latency, vorinostat may be a useful therapeutic to inhibit the negative regulatory effects on synaptic plasticity in HIV infected nicotine abusers. PMID:24886748

2014-01-01

322

HIV+ and HIV? youth living in group homes in South Africa need more psychosocial support  

PubMed Central

Orphans and vulnerable youth who live in group homes are at risk of poor mental health and sexual and drug-using behaviors that increase the risk of HIV transmission. This study explores factors related to this risk among youth living in group homes (“children’s homes”) for orphans and vulnerable children in South Africa, a country afflicted by high levels of parental loss due to HIV. The study explores 1) knowledge and attitudes about HIV, 2) social support, 3) communication with group home caregivers, and 4) the relevance of an existing evidence-based HIV prevention and mental health promotion program to situations where sexual and drug risk behaviors can occur. In-depth qualitative individual interviews were conducted with 20 youth (age 10 to 16 years) residing in two children’s homes in Durban, South Africa. Content analysis focused on critical themes related to coping and prevention of risk activities. Respondents exhibited inconsistent and incomplete knowledge of HIV transmission and prevention. They displayed positive attitudes toward people living with HIV, but reported experiencing or witnessing HIV-related stigma. Participants witnessed substance use and romantic/sexual relationships among their peers; few admitted to their own involvement. While relationships with childcare workers were central to their lives, youth reported communication barriers related to substance use, sex, HIV, and personal history (including parental loss, abuse, and other trauma). In conclusion, these qualitative data suggest that evidence-based HIV prevention programs that bring caregivers and youth together to improve communication, HIV knowledge, social support, youth self-esteem, and health care, reduce sexual and drug risk behaviors, and strengthen skills related to negotiating situations of sexual and substance use possibility could benefit youth and childcare workers in children’s homes. PMID:24039626

Nestadt, D.F.; Alicea, S.; Petersen, I.; John, S.; Myeza, N.P.; Nicholas, S.W.; Cohen, L.G.; Holst, H.; Bhana, A.; McKay, M.M.; Abrams, E.J.; Mellins, C.A.

2013-01-01

323

Molecular Recognition of CCR5 by an HIV-1 gp120 V3 Loop  

PubMed Central

The binding of protein HIV-1 gp120 to coreceptors CCR5 or CXCR4 is a key step of the HIV-1 entry to the host cell, and is predominantly mediated through the V3 loop fragment of HIV-1 gp120. In the present work, we delineate the molecular recognition of chemokine receptor CCR5 by a dual tropic HIV-1 gp120 V3 loop, using a comprehensive set of computational tools predominantly based on molecular dynamics simulations and free energy calculations. We report, what is to our knowledge, the first complete HIV-1 gp120 V3 loop : CCR5 complex structure, which includes the whole V3 loop and the N-terminus of CCR5, and exhibits exceptional agreement with previous experimental findings. The computationally derived structure sheds light into the functional role of HIV-1 gp120 V3 loop and CCR5 residues associated with the HIV-1 coreceptor activity, and provides insights into the HIV-1 coreceptor selectivity and the blocking mechanism of HIV-1 gp120 by maraviroc. By comparing the binding of the specific dual tropic HIV-1 gp120 V3 loop with CCR5 and CXCR4, we observe that the HIV-1 gp120 V3 loop residues 13–21, which include the tip, share nearly identical structural and energetic properties in complex with both coreceptors. This result paves the way for the design of dual CCR5/CXCR4 targeted peptides as novel potential anti-AIDS therapeutics. PMID:24763408

Tamamis, Phanourios; Floudas, Christodoulos A.

2014-01-01

324

HIV-negative Men-who-Have-Sex-with-Men who Bareback are Concerned about HIV Infection: Implications for HIV Risk Reduction Interventions  

PubMed Central

The emergence of barebacking (intentional unprotected anal intercourse in situations where there is risk of HIV infection) among men who have sex with men (MSM) has been partially attributed to a decrease in HIV-related concerns due to improved anti-retroviral treatment. It is important to understand the level of concern these men have regarding HIV infection because it can affect their interest in risk reduction behaviors as well as their possible engagement in risk reduction interventions. As part of a study on MSM who use the Internet to seek sexual partners, 89 ethnic and racially diverse men who reported never having an HIV-positive test result completed an in-depth qualitative interview and a computer-based quantitative assessment. Of the 82 men who were asked about concerns of HIV infection during the qualitative interviews, 30 expressed “significant concern” about acquiring HIV, while 42 expressed “moderate concern,” and 10 expressed “minimal concern. Themes that emerged across the different levels of concern were their perceptions of the severity of HIV infection, having friends who are HIV positive, and their own vulnerability to HIV infection. However, these themes differed depending on the level of concern. Among the most frequently mentioned approaches to decrease risk of HIV infection, participants mentioned avoiding HIV-positive sex partners, limiting the number of partners with whom they barebacked, and not allowing partners to ejaculate inside their rectum. Findings suggest that many MSM who bareback would be amenable to HIV prevention efforts that do not depend solely on condom use. PMID:22218787

Balán, Iván C.; Carballo-Diéguez, Alex; Ventuneac, Ana; Remien, Robert H.; Dolezal, Curtis; Ford, Jordan

2012-01-01

325

Virus inactivation/elimination in therapeutic protein concentrates.  

PubMed

Concern for virus transmission from intravenous biological products, derived from natural and biotechnological sources, has prompted us to investigate various methods for virus inactivation while preserving the biological activity of the therapeutic entity. This concern is currently acute regarding the presence of HIV in purified human plasma protein concentrates. Four different methods of virus removal (1) heating in solution; (2) use of lipid solvents; (3) low pH treatment, and (4) partitioning during purification, are reported for various plasma proteins that have been spiked with model viruses. General virus inactivation strategies for therapeutic protein concentrates are discussed. PMID:2910652

Mitra, G; Dobkin, M B; Wong, M F; Mozen, M M

1989-01-01

326

[Lines of research in the treatment of HIV infection].  

PubMed

Antiretroviral treatment have completely modified the face of HIV infection. Research of new therapeutic approaches during infection focus on the use of antiretroviral drugs and on new targets, treatment of immune activation and viral eradication. Recommendations for c-ART initiation are now broader. Future development in the area of antiretroviral therapy concern their use for prevention and the design of long-acting drugs. Extensive research efforts have led to the proposal of strategies that aim to treat immune activation which favor the occurrence of non AIDS defining disease and to eradicate HIV through the use of several different strategies (therapeutic vaccines, anti latency compounds). Results of these new approaches remain preliminary and antiretroviral treatment remain the only weapon to fight HIV infection. PMID:25510135

Saidani, Maryline; Leličvre, Jean-Daniel

2014-10-01

327

Frequency variation among sub-Saharan populations in virus restriction gene, BST-2 proximal promoter polymorphisms: implications for HIV-1 prevalence differences among African countries.  

PubMed

The present study reports promoter variants in four sub-Saharan African populations that may affect BST-2 gene regulation. Recently, an in/del within the BST-2 promoter has been associated with HIV-1 disease progression in a Spanish cohort. Hence, we sequenced the proximal promoter region of the BST-2 gene in 581 individuals from South Africa, Zimbabwe, Malawi, and Cameroon. Seven SNPs were identified: rs28413176 (+26i6/?6); rs28413175 (-160i1/?1), -187A>G (nucleotide position -17516614); rs28413174 (-193G>A); rs73921425 (-199G>A); rs12609479 (-201C>T); and rs112492472 (-225C>T). The -199A and -225T alleles showed interesting trends across the sub-Saharan continent. Using predictive bioinformatics tools, we show that allelic variation at -199 and -201 potentially affect key transcription factor binding sites including bHLH, c-Myb, and E47. Importantly, data available from the ENCODE study gave further credence to our hypothesis of transcriptional regulation of BST-2 by a bHLH TF such as Mxi1. The possible repressive transcriptional effect of Mxi1 combined with the allelic frequency trend seen at -199 between African populations overlays well with current HIV-1 prevalence data, and may be a contributing factor to this phenomenon. The differences in HIV-1 prevalence in African countries could be, in part, due to distribution of genetic variants that affect susceptibility to HIV-1. Our findings therefore have substantive value for the design of future diagnostics for global health oriented diagnostics for HIV-1 susceptibility, and rational therapeutics on the critical path to personalized medicine in the African continent. As HIV-1 epidemiology vastly impacts human populations around the world, the population genomics strategy we have utilized herein can have value for other global regions as well. PMID:24601767

Skelton, Michelle M; Kampira, Elizabeth E; Wonkam, Ambroise A; Mhandire, Kudakwashe K; Kumwenda, Johnstone J; Duri, Kerina K; Dandara, Collet C

2014-07-01

328

Murders and HIV.  

PubMed

Investigators have dismissed the previously reported HIV diagnosis links in two prominent homicide cases. Serial murderer [name removed], who shot renowned fashion designer Gianni Versace and four other men, was thought to have killed out of rage because his own life was doomed by HIV. Tests conducted during [name removed]'s autopsy revealed that he was not HIV-positive. [Name removed], who was HIV-positive, had unprotected sex with more than 100 women and girls and did not inform them of his HIV-status. [Name removed] infected at least 30 women with HIV through unprotected sex. When [name removed] was found murdered in St. Louis, MO, police suspected that the motive was revenge for intentional HIV transmission. It was later determined that [name removed] was the victim of a street robbery. PMID:11364597

1997-08-22

329

Healthcare Economics in HIV.  

PubMed

In an era of cost-consciousness in the delivery of medical care, the economics of healthcare delivery for HIV-infected persons has been an area of active interest. Interested parties include the payors of HIV care, particularly public insurers, who are paying for an increasing amount of the overall cost of HIV care in the US; providers of care, many of whom are finding it increasingly difficult to provide HIV care in a capitated market; and those persons who are HIV-infected and increasingly caught in the economic turmoil of the HIV healthcare marketplace. This paper will review the literature published over the past year regarding the economics of healthcare for HIV in the US. PMID:11095880

Moore

2000-08-01

330

What Is HIV/AIDS?  

MedlinePLUS

... HIV/AIDS? Translate Text Size Print What Is HIV/AIDS? What Is HIV? â??HIVâ?ť stands for Human Immunodeficiency Virus. To ... Should I Do if I Think I Have HIV? Find HIV/AIDS Prevention & Service Providers Enter your ...

331

Sickle cell disease is associated with decreased HIV but higher HBV and HCV comorbidities in US hospital discharge records: a cross-sectional study  

PubMed Central

Objective Some studies suggest that HIV infection progresses slowly in patients with sickle cell disease (SCD). The authors aimed to determine the relationships between SCD and HIV infection. Methods National Hospital Discharge Survey data from adult Africane–Americans in the period of 1997–2009 were analysed. The comorbidities of SCD with HIV infections in hospital discharges were analysed. Multiple logistic regression was used to test the association between SCD and HIV. For comparative purposes, the relationships of SCD with hepatitis B virus (HBV) and hepatitis C virus (HCV) were also assessed. Results 423 431 records were divided into two time periods 1997–2003 (53% of records) and 2004–2009 (47% of records). The frequency of HIV diagnosis was lower in patients with SCD (1.5% vs 3.3% in patients without SCD). In logistic regression, SCD diagnosis was associated with an OR of 0.24 (95% CI 0.18 to 0.32) for HIV diagnosis in the first period and with an OR of 0.31 (95% CI 0.22 to 0.42) in the second period. In contrast, SCD was associated with higher risk of HCV (OR=2.01, 95% CI 1.56 to 2.59 in the first period and OR=2.12, 95% CI 1.71 to 2.63 in the second period). SCD was also associated with a higher risk of HBV (OR=1.15, 95% CI 0.72 to 1.83 in the first period and OR=1.82, 95% CI 1.24 to 2.68 in the second period). Conclusions The lower risk of HIV comorbidity, but not HCV and HBV, with SCD is consistent with the possibility that SCD has a unique effect in altering the risk of HIV infection or progression. Investigation of how the haemolytic and immunological changes of SCD influence HIV might lead to new therapeutic or preventive approaches. PMID:22628662

Nouraie, Mehdi; Nekhai, Sergei; Gordeuk, Victor R

2012-01-01

332

HIV co-receptor inhibitors as novel class of anti-HIV drugs  

Microsoft Academic Search

Entry inhibitors constitute a new class of drugs to treat infection by human immunodeficiency virus type 1 (HIV-1). The first member of this class, enfuvirtide, previously known as T-20 and targeting gp41, has now been licensed for therapeutic use. Several other entry inhibitors are in various stages of pre-clinical or clinical development. In this review we focus on the chemokine

Dominique Schols

2006-01-01

333

Types of HIV/AIDS Antiretroviral Drugs  

MedlinePLUS

... reverse transcriptase (RT) from converting single-stranded HIV RNA into double-stranded HIV DNA?a process called ... RT, interfering with its ability to convert HIV RNA into HIV DNA Integrase Inhibitors block the HIV ...

334

HIV1–specific immune responses in subjects who temporarily contain virus replication after discontinuation of highly active antiretroviral therapy  

Microsoft Academic Search

Therapeutic intervention with highly active antiretroviral therapy (HAART) can lead to suppression of HIV-1 plasma viremia to undetectable levels for 3 or more years. However, adherence to complex drug regimens can prove problematic, and subjects may temporarily discontinue HAART for variable periods. We studied 6 HIV-1-infected individuals who stopped therapy. Off HAART, levels of viremia were suppressed to fewer than

Gabriel M. Ortiz; Douglas F. Nixon; Alexandra Trkola; James Binley; Xia Jin; Sebastian Bonhoeffer; Peter J. Kuebler; Sean M. Donahoe; Marie-Ange Demoitie; William M. Kakimoto; Tom Ketas; Brian Clas; Jonas J. Heymann; Linqi Zhang; Yunzhen Cao; Arlene Hurley; John P. Moore; David D. Ho; Martin Markowitz

1999-01-01

335

Simultaneous determination of 16 anti-HIV drugs in human plasma by high-performance liquid chromatography  

Microsoft Academic Search

Therapeutic drug monitoring (TDM) is pivotal to improve the management of HIV infection. Here, a HPLC–UV method has been developed to quantify simultaneously seven HIV protease inhibitors (amprenavir, atazanavir, indinavir, lopinavir, nelfinavir, ritonavir, and saquinavir; PIs), seven nucleoside reverse transcriptase inhibitors (abacavir, didanosine, emtricitabine, lamivudine, stavudine, zalcitabine, and zidovudine; NRTIs), and two non-nucleoside reverse transcriptase inhibitors (efavirenz and nevirapine; NNRTIs)

Stefania Notari; Alessio Bocedi; Giuseppe Ippolito; Pasquale Narciso; Leopoldo Paolo Pucillo; Gianna Tossini; Raffaele Perrone Donnorso; Francesco Gasparrini; Paolo Ascenzi

2006-01-01

336

A review of HIV antiretroviral adherence and intervention studies among HIV-infected youth.  

PubMed

Advances in antiretroviral medications have resulted in precipitous declines in HIV-associated morbidity and mortality; however, high levels of adherence are crucial to the success of HIV therapies. This article reviews published studies in the United States on HIV-infected youth (ages 13 to 24 years), focusing on adherence to antiretroviral regimens and interventions designed to enhance adherence. A systematic search yielded 21 articles published between 1999 and 2008 that reported data on medication adherence in HIV-infected youth, of which 7 described unique interventions to enhance medication adherence. Five thematic areas were identified to classify factors associated with adherence. Findings suggest psychosocial factors, in particular depression and anxiety, were consistently associated with poorer adherence across studies. Three types of adherence interventions with HIV-infected youth were found. Results suggest that examining adherence within the broader contextual issues present in the lives of youth, including HIV stigma and disclosure, caregiver stress, peer relations, mental health and substance use, and length of time on medications, may be most important to understanding how best to intervene with adherence among this population. Secondary HIV prevention interventions for youth represent a possible mode through which to deliver individually tailored adherence skill building and counseling to improve medication adherence. PMID:19270345

Reisner, Sari L; Mimiaga, Matthew J; Skeer, Margie; Perkovich, Brandon; Johnson, Carey V; Safren, Steven A

2009-01-01

337

Mechanistic insights on immunosenescence and chronic immune activation in HIV-tuberculosis co-infection.  

PubMed

Immunosenescence is marked by accelerated degradation of host immune responses leading to the onset of opportunistic infections, where senescent T cells show remarkably higher ontogenic defects as compared to healthy T cells. The mechanistic association between T-cell immunosenescence and human immunodeficiency virus (HIV) disease progression, and functional T-cell responses in HIV-tuberculosis (HIV-TB) co-infection remains to be elaborately discussed. Here, we discussed the association of immunosenescence and chronic immune activation in HIV-TB co-infection and reviewed the role played by mediators of immune deterioration in HIV-TB co-infection necessitating the importance of designing therapeutic strategies against HIV disease progression and pathogenesis. PMID:25674514

Shankar, Esaki M; Velu, Vijayakumar; Kamarulzaman, Adeeba; Larsson, Marie

2015-02-12

338

Mechanistic insights on immunosenescence and chronic immune activation in HIV-tuberculosis co-infection  

PubMed Central

Immunosenescence is marked by accelerated degradation of host immune responses leading to the onset of opportunistic infections, where senescent T cells show remarkably higher ontogenic defects as compared to healthy T cells. The mechanistic association between T-cell immunosenescence and human immunodeficiency virus (HIV) disease progression, and functional T-cell responses in HIV-tuberculosis (HIV-TB) co-infection remains to be elaborately discussed. Here, we discussed the association of immunosenescence and chronic immune activation in HIV-TB co-infection and reviewed the role played by mediators of immune deterioration in HIV-TB co-infection necessitating the importance of designing therapeutic strategies against HIV disease progression and pathogenesis. PMID:25674514

Shankar, Esaki M; Velu, Vijayakumar; Kamarulzaman, Adeeba; Larsson, Marie

2015-01-01

339

Gene Therapy Strategies for HIV/AIDS: Preclinical Modeling in Humanized Mice  

PubMed Central

In the absence of an effective vaccine and lack of a complete cure, gene therapy approaches to control HIV infection offer feasible alternatives. Due to the chronic nature of infection, a wide window of opportunity exists to gene modify the HIV susceptible cells that continuously arise from the bone marrow source. To evaluate promising gene therapy approaches that employ various anti-HIV therapeutic molecules, an ideal animal model is necessary to generate important efficacy and preclinical data. In this regard, the humanized mouse models that harbor human hematopoietic cells susceptible to HIV infection provide a suitable in vivo system. This review summarizes the currently used humanized mouse models and different anti-HIV molecules utilized for conferring HIV resistance. Humanized mouse models are compared for their utility in this context and provide perspectives for new directions. PMID:24351796

Bennett, Michael S.; Akkina, Ramesh

2013-01-01

340

MicroRNAs and their potential involvement in HIV infection  

PubMed Central

Treatment and cure of human immunodeficiency virus-1(HIV-1) infection remains one of the greatest therapeutic challenges due to its persistent infection, which often leads to acquired immunodeficiency syndrome (AIDS). Although it has been 28 years since the discovery of the virus, the development of an effective vaccine is still years away. Relatively newly discovered microRNAs (miRNA) are a family of small non-coding RNAs that can regulate gene expression primarily by binding to the 3? untranslated region (UTR) of targeted transcripts. Understanding how HIV-1 infection affects the host miRNA pathway could generate new insights into the basic mechanisms underlying HIV-1-mediated pathologies and T-lymphocyte depletion. Here, we review literature related to the biogenesis of HIV-1 encoded miRNAs, cellular miRNAs that can directly target HIV-1 or essential cellular factors required for HIV-1 replication. We also discuss the feasibility of using miRNAs for HIV-1 therapy. PMID:21862142

Sun, Guihua; Rossi, John J.

2011-01-01

341

Molecular Mechanisms of Liver Fibrosis in HIV/HCV Coinfection  

PubMed Central

Chronic hepatitis C virus (HCV) infection is an important cause of morbidity and mortality in people coinfected with human immunodeficiency virus (HIV). Several studies have shown that HIV infection promotes accelerated HCV hepatic fibrosis progression, even with HIV replication under full antiretroviral control. The pathogenesis of accelerated hepatic fibrosis among HIV/HCV coinfected individuals is complex and multifactorial. The most relevant mechanisms involved include direct viral effects, immune/cytokine dysregulation, altered levels of matrix metalloproteinases and fibrosis biomarkers, increased oxidative stress and hepatocyte apoptosis, HIV-associated gut depletion of CD4 cells, and microbial translocation. In addition, metabolic alterations, heavy alcohol use, as well drug use, may have a potential role in liver disease progression. Understanding the pathophysiology and regulation of liver fibrosis in HIV/HCV co-infection may lead to the development of therapeutic strategies for the management of all patients with ongoing liver disease. In this review, we therefore discuss the evidence and potential molecular mechanisms involved in the accelerated liver fibrosis seen in patients coinfected with HIV and HCV. PMID:24865485

Mastroianni, Claudio M.; Lichtner, Miriam; Mascia, Claudia; Zuccalŕ, Paola; Vullo, Vincenzo

2014-01-01

342

[Kidney transplant in patients with HIV infection].  

PubMed

Until recently, human immunodeficiency virus (HIV) infection was an absolute contraindication to solid organ transplantation because it was feared that the anti-rejection therapy could result in accelerated HIV disease. At the end of the 1990s it became clear that HIV infection, once deemed a fatal disease, could be effectively turned into a chronic condition by the use of highly active antiretroviral therapy. Since then, the mortality rate from opportunistic infections has decreased dramatically, while liver and renal insufficiency have become the major causes of morbidity and mortality in these patients in the long term. A growing number of HIV patients develop end-stage renal disease secondary to immune-mediated glomerulonephritis, HIV-associated nephropathy, nephrotoxic effects induced by antiretroviral medication, or diabetic and vascular nephropathy, and therefore need maintenance dialysis. For this reason we have to reconsider kidney transplant as a possible treatment option. During the last decade, the results of many studies have shown that transplantation can be safe and effective as long as the HIV infection is effectively controlled by antiretroviral therapy. The short- and medium-term patient and graft survival rates in HIV-positive transplant recipients are comparable with those of the overall transplant population, but the incidence of acute rejection episodes is higher. The main clinical problem in the management of HIV-positive transplant recipients originates from the interference between immunosuppressive regimens and antiretroviral drugs. Thus, a close collaboration between infectious disease specialists and nephrologists is mandatory in order to optimize transplantation programs in these patients. PMID:22843153

Bossini, Nicola; Sandrini, Silvio; Valerio, Francesca

2012-01-01

343

HTLV-1/-2 and HIV-1 co-infections: retroviral interference on host immune status  

PubMed Central

The human retroviruses HIV-1 and HTLV-1/HTLV-2 share similar routes of transmission but cause significantly different diseases. In this review we have outlined the immune mediated mechanisms by which HTLVs affect HIV-1 disease in co-infected hosts. During co-infection with HIV-1, HTLV-2 modulates the cellular microenvironment favoring its own viability and inhibiting HIV-1 progression. This is achieved when the HTLV-2 proviral load is higher than that of HIV-1, and thanks to the ability of HTLV-2 to: (i) up-regulate viral suppressive CCL3L1 chemokine expression; (ii) overcome HIV-1 capacity to activate the JAK/STAT pathway; (iii) reduce the activation of T and NK cells; (iv) modulate the host miRNA profiles. These alterations of immune functions have been mainly attributed to the effects of the HTLV-2 regulatory protein Tax and suggest that HTLV-2 exerts a protective role against HIV-1 infection. Contrary to HIV-1/HTLV-2, the effect of HIV-1/HTLV-1 co-infection on immunological and pathological conditions is still controversial. There is evidence that indicates a worsening of HIV-1 infection, while other evidence does not show clinically relevant effects in HIV-positive people. Possible differences on innate immune mechanisms and a particularly impact on NK cells are becoming evident. The differences between the two HIV-1/HTLV-1 and HIV-1/HTLV-2 co-infections are highlighted and further discussed. PMID:24391628

Pilotti, Elisabetta; Bianchi, Maria V.; De Maria, Andrea; Bozzano, Federica; Romanelli, Maria G.; Bertazzoni, Umberto; Casoli, Claudio

2013-01-01

344

Towards Combination HIV Prevention for Injection Drug Users: Addressing Addictophobia, Apathy and Inattention  

PubMed Central

Purpose of the review Recent breakthroughs in HIV-prevention science led us to evaluate the current state of combination HIV-prevention for injection drug users (IDUs). We review the recent literature focusing on possible reasons why coverage of prevention interventions for HIV, HCV and tuberculosis among IDUs remains dismal. We make recommendations for future HIV research and policy. Recent findings IDUs disproportionately under-utilize VCT, primary care and ART, especially in countries that have the largest burden of HIV among IDUs. IDUs present later in the course of HIV infection and experience greater morbidity and mortality. Why are IDUs under-represented in HIV-prevention research, access to treatment for both HIV and addiction, and access to HIV combination prevention? Possible explanations include addictophobia, apathy, and inattention, which we describe in the context of recent literature and events. Summary This commentary discusses the current state of HIV-prevention interventions for IDUs including, VCT, NSP, OST, ART and PrEP, and discusses ways to work towards true combination HIV-prevention for IDU populations. Communities need to overcome tacit assumptions that IDUs can navigate through systems that are maintained as separate silos, and take a rights-based approach to HIV-prevention to ensure that IDUs have equitable access to life-saving prevention and treatments. PMID:22498479

Strathdee, Steffanie A.; Shoptaw, Steven; Dyer, Typhanye Penniman; Quan, Vu Minh; Aramrattana, Apinun

2013-01-01

345

Therapeutics in Huntington's Disease.  

PubMed

OPINION STATEMENT: There is no specific treatment for Huntington's disease (HD). Its many symptoms of motor, psychiatric, and cognitive deterioration are managed with symptomatic relief, rehabilitation, and support. The only drug approved by the US Food and Drug Administration (FDA) for the treatment of HD is an antichoreic agent, tetrabenazine, but this drug is used sparingly because of uneasiness regarding its propensity to cause depression and suicidality in this population, which is already at risk for these complications. Neuroleptics are still first-line treatments for chorea accompanied by comorbid depression and/or behavioral or psychotic symptoms, as is often the case. Psychiatric features, which have a significant impact on a patient's professional and personal life, often become the major focus of management. In addition to neuroleptics, commonly used medications include antidepressants, mood stabilizers, anxiolytics, and psychostimulants. In contrast, few treatment options are available for cognitive impairment in HD; this remains an important and largely unmet therapeutic need. HD patients typically lack insight into their disease manifestations, failing to recognize their need for treatment, and possibly even arguing against it. Multipurpose medications are employed advantageously to simplify the medication regimen, so as to facilitate compliance and not overwhelm the patient. For example, haloperidol can be prescribed for a patient with chorea, agitation, and anorexia, rather than targeting each symptom with a different drug. This approach also limits the potential for adverse effects, which can be difficult to distinguish from the features of the disease itself. With HD's complexity, it is best managed with a multidisciplinary approach that includes a movement disorders specialist, a genetic counselor, a mental health professional, a physical therapist, and a social worker for support and coordination of services. As the disease progresses, there may be need for other specialists, such as a speech and occupational therapist, a nutritionist for weight loss, and ultimately, a palliative care specialist. PMID:22314929

Killoran, Annie; Biglan, Kevin M

2012-02-01

346

TALEN Knockout of the PSIP1 Gene in Human Cells: Analyses of HIV-1 Replication and Allosteric Integrase Inhibitor Mechanism  

PubMed Central

ABSTRACT HIV-1 utilizes the cellular protein LEDGF/p75 as a chromosome docking and integration cofactor. The LEDGF/p75 gene, PSIP1, is a potential therapeutic target because, like CCR5, depletion of LEDGF/p75 is tolerated well by human CD4+ T cells, and knockout mice have normal immune systems. RNA interference (RNAi) has been useful for studying LEDGF/p75, but the potent cofactor activity of small protein residua can be confounding. Here, in human cells with utility for HIV research (293T and Jurkat), we used transcription activator-like effector nucleases (TALENs) to completely eradicate all LEDGF/p75 expression. We performed two kinds of PSIP1 knockouts: whole-gene deletion and deletion of the integrase binding domain (IBD)-encoding exons. HIV-1 integration was inhibited, and spreading viral replication was severely impaired in PSIP1?/? Jurkat cells infected at high multiplicity. Furthermore, frameshifting the gene in the first coding exon with a single TALEN pair yielded trace LEDGF/p75 levels that were virologically active, affirming the cofactor's potency and the value of definitive gene or IBD exon segment deletion. Some recent studies have suggested that LEDGF/p75 may participate in HIV-1 assembly. However, we determined that assembly of infectious viral particles is normal in PSIP1?/? cells. The potency of an allosteric integrase inhibitor, ALLINI-2, for rendering produced virions noninfectious was also unaffected by total eradication of cellular LEDGF/p75. We conclude that HIV-1 particle assembly and the main ALLINI mechanism are LEDGF/p75 independent. The block to HIV-1 propagation in PSIP1?/? human CD4+ T cells raises the possibility of gene targeting PSIP1 combinatorially with CCR5 for HIV-1 cure. IMPORTANCE LEDGF/p75 dependence is universally conserved in the retroviral genus Lentivirus. Once inside the nucleus, lentiviral preintegration complexes are thought to attach to the chromosome when integrase binds to LEDGF/p75. This tethering process is largely responsible for the 2-fold preference for integration into active genes, but the cofactor's full role in the lentiviral life cycle is not yet clear. Effective knockdowns are difficult because even trace residua of this tightly chromatin-bound protein can support integration cofactor function. Here, in experimentally useful human cell lines, we used TALENs to definitively eradicate LEDGF/p75 by deleting either all of PSIP1 or the exons that code for the integrase binding domain. HIV-1 replication was severely impaired in these PSIP1 knockout cells. Experiments in these cells also excluded a role for LEDGF/p75 in HIV-1 assembly and showed that the main ALLINI mechanism is LEDGF/p75 independent. Site-specific gene targeting of PSIP1 may have therapeutic potential for HIV-1 disease. PMID:24942577

Morrison, James H.; Saenz, Dyana T.; Fuchs, James R.; Kvaratskhelia, Mamuka; Ekker, Stephen C.

2014-01-01

347

HIV-Specific Criminal Laws  

MedlinePLUS

... A-Z Topics Share Compartir HIV-Specific Criminal Laws During the early years of the HIV epidemic, ... number of states implemented HIV-specific criminal exposure laws. These laws impose criminal penalties on people living ...

348

Research Report: HIV/AIDS  

MedlinePLUS

... Home » HIV/AIDS » Letter from the Director HIV/AIDS Email Facebook Twitter Letter from the Director Human immunodeficiency virus (HIV) — the virus that causes acquired immune deficiency syndrome (AIDS) — has been with us for three decades now. ...

349

HIV, AIDS, and the Future  

MedlinePLUS

... Navigation Bar Home Current Issue Past Issues HIV / AIDS HIV, AIDS, and the Future Past Issues / Summer 2009 Table ... and your loved ones from HIV/AIDS. The AIDS Memorial Quilt In 1987, a total of 1, ...

350

HIV/AIDS and Alcohol  

MedlinePLUS

... Psychiatric Disorders Other Substance Abuse HIV/AIDS HIV/AIDS Human immunodeficiency virus (HIV) targets the body’s immune ... and often leads to acquired immune deficiency syndrome (AIDS). Each year in the United States, between 55, ...

351

Legal Disclosure of HIV Status  

MedlinePLUS

... Legal Disclosure Translate Text Size Print Legal Disclosure HIV Disclosure Policies and Procedures If your HIV test ... aids.gov • facing.aids.gov • providertools.aids.gov • HIV/AIDS Service Locator Locator Widgets • Instructions • API Find ...

352

Depression and HIV/AIDS  

MedlinePLUS

... see the NIMH booklet on Depression . What is HIV/AIDS? Human immunodeficiency virus (HIV) is the virus ... they can function normally. How are depression and HIV/AIDS linked? Studies show that people who are ...

353

Medicare and HIV/AIDS  

MedlinePLUS

... research and analysis on health issues. February 2009 Medicare and HIV/AIDS Medicare, the federal health insurance ... it began to pay for prescription drugs. 3 Medicare Beneficiaries with HIV Most people with HIV on ...

354

Pathogenesis and Treatment of HIV Lipohypertrophy  

PubMed Central

Purpose of Review This review addresses our current understanding of the pathogenesis of HIV associated lipohypertrophy, and describes an evidence-based approach to treatment. Recent Findings Although the pathogenesis of HIV associated lipohypertrophy remains elusive, recent clinical and laboratory investigations in fatty acid metabolism and growth hormone dynamics have furthered our understanding of the condition. These findings have also paved the way for new therapeutic interventions, of which tesamorelin, an analogue of growth hormone-releasing hormone, has gained recognition as a promising treatment strategy against visceral fat accumulation. Recent randomized placebo-controlled trials of tesamorelin demonstrated significant reductions in visceral adipose tissue, improvement in lipid parameters, and no adverse effects on glucose tolerance. Optimal therapeutic dosing and treatment duration, though, are not yet known. Whether treatment with GHRH-analogues will translate into improved long-term metabolic and cardiovascular outcomes also remains to be seen. Summary Although the pathogenesis of HIV lipohypertrophy remains unclear, several theories and observations have led to the development of treatment strategies to counter fat accumulation and its accompanying metabolic complications. Based on clinical trials, analogues of the GH/GHRH axis appear to be most effective in reducing visceral adipose tissue. PMID:21124215

Leung, Vivien L.; Glesby, Marshall J.

2013-01-01

355

Towards Therapeutic Arteriogenesis  

Cancer.gov

Arteriogenesis or the formation of arterial conduits is a promising therapeutic approach to the treatment of a number of ischemic vascular diseases. However, the molecular basis of this process remains poorly understood.

356

Therapeutics for Bowel Disorders  

Cancer.gov

The National Cancer Institute''s Laboratory of Metabolism is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize therapeutics that ameliorate bowel disorders.

357

Therapeutic development in psoriasis.  

PubMed

Advances in molecular biology have provided the basis for development of new therapeutic approaches to psoriasis. New, more effective therapies target specific molecules in the inflammatory cascade involved in the pathogenesis of psoriasis.The biologic era of psoriasis therapy began with inhibitors of T-cell activation, tumor necrosis factor-?, and interleukin (IL)-12/23. Continued investigation has led to therapies and therapeutic candidates that target IL-17, IL-23, phosphodiesterase-4, and isomers of Janus kinase. PMID:25268599

Sobell, Jeffrey M; Leonardi, Craig L

2014-06-01

358

Therapeutic Endoscopic Ultrasound  

PubMed Central

Endoscopic ultrasound (EUS) is a viable and often preferred alternative to interventional and radiologic procedures, and the therapeutic applications of EUS continue to evolve. This evolution was catalyzed by the introduction of linear echoendoscopes that provide continuous imaging and observation of needles and by therapeutic devices that pass through large-caliber working channels. In this paper, we will discuss the spectrum of EUS-guided interventions that are currently available and in development. PMID:23293554

Abu Dayyeh, Barham K.

2012-01-01

359

Barriers and Facilitators of HIV Disclosure: Perspectives from HIV-Infected Men Who Have Sex with Men.  

PubMed

HIV disclosure among sexually active HIV-infected men who have sex with men (MSM) is a complex phenomenon. To better understand factors that impact the decision-making process regarding HIV disclosure among HIV-infected MSM, the present study analyzed content from previously conducted counseling sessions where HIV disclosure was selected as the primary focus of the session. The counselor/participant dialogue was audio-recorded, transcribed, and analyzed qualitatively using content analysis. Factors identified as barriers that deter HIV-infected MSM from disclosing include rejection, issues of confidentiality, possible missed sexual opportunities, partner's HIV status, deferred responsibility, sexual partner type, and public sex environments. Participants identified ethical obligation, the potential for a dating relationship, timing of disclosure, and bidirectional communication as facilitators of disclosure. Findings can be used for policy development as well as to guide social workers and other healthcare providers' assessment and development of clinical interventions addressing sexual health among HIV-infected MSM as it relates to HIV disclosure. PMID:23671405

Driskell, Jeffrey R; Salomon, Elizabeth; Mayer, Kenneth; Capistrant, Benjamin; Safren, Steven

2008-01-01

360

Barriers and Facilitators of HIV Disclosure: Perspectives from HIV-Infected Men Who Have Sex with Men  

PubMed Central

HIV disclosure among sexually active HIV-infected men who have sex with men (MSM) is a complex phenomenon. To better understand factors that impact the decision-making process regarding HIV disclosure among HIV-infected MSM, the present study analyzed content from previously conducted counseling sessions where HIV disclosure was selected as the primary focus of the session. The counselor/participant dialogue was audio-recorded, transcribed, and analyzed qualitatively using content analysis. Factors identified as barriers that deter HIV-infected MSM from disclosing include rejection, issues of confidentiality, possible missed sexual opportunities, partner’s HIV status, deferred responsibility, sexual partner type, and public sex environments. Participants identified ethical obligation, the potential for a dating relationship, timing of disclosure, and bidirectional communication as facilitators of disclosure. Findings can be used for policy development as well as to guide social workers and other healthcare providers’ assessment and development of clinical interventions addressing sexual health among HIV-infected MSM as it relates to HIV disclosure. PMID:23671405

Driskell, Jeffrey R.; Salomon, Elizabeth; Mayer, Kenneth; Capistrant, Benjamin; Safren, Steven

2013-01-01

361

The Warburg effect: molecular aspects and therapeutic possibilities.  

PubMed

It has been about nine decades since the proposal of Otto Warburg on the metabolism of cancer cells. Unlike normal cells which undergo glycolysis and oxidative phosphorylation in the presence of oxygen, proliferating and cancer cells exhibit an increased uptake of glucose and increased rate of glycolysis and predominantly undergo lactic acid fermentation. Whether this phenomenon is the consequence of genetic dysregulation in cancer or is the cause of cancer still remains unknown. However, there is certainly a strong link between the genetic factors, epigenetic modulation, cancer immunosurveillance and the Warburg effect, which will be discussed in this review. Dichloroacetate and 3-bromopyruvate are among the substances that have been studied as potential cancer therapies. With our expanding knowledge of cellular metabolism, therapies targeting the Warburg effect appear very promising. This review discusses different aspects of these emerging therapies. PMID:25253100

Ngo, Hanh; Tortorella, Stephanie M; Ververis, Katherine; Karagiannis, Tom C

2015-04-01

362

Human endogenous retroviruses and cancer: Causality and therapeutic possibilities  

PubMed Central

A substantial part of the human genome is derived from transposable elements; remnants of ancient retroviral infections. Conservative estimates set the percentage of human endogenous retroviruses (HERVs) in the genome at 8%. For the most part, the interplay between mutations, epigenetic mechanisms and posttranscriptional regulations silence HERVs in somatic cells. We first highlight mechanisms by which activation of members of several HERV families may be associated with tumor development before discussing the arising chances for both diagnosis and therapy. It has been shown that at least in some cases, tumor cells expressing HERV open reading frames (ORFs) thus gain tumor-promoting functions. However, since these proteins are not expressed in healthy tissues, they become prime target structures. Of potential pharmacological interest are the prevention of HERV transposition, the inhibition of HERV-encoded protein expression and the interference with these proteins’ activities. Evidence from recent studies unequivocally proves that HERV ORFs represent a very interesting source of novel tumor-specific antigens with even the potential to surpass entity boundaries. The development of new tumor (immune-) therapies is a very active field and true tumor-specific targets are of outstanding interest since they minimize the risk of autoimmunity and could reduce side effects. Finally, we postulate on main future research streams in order to stimulate discussion on this hot topic. PMID:23155332

Mullins, Christina S; Linnebacher, Michael

2012-01-01

363

USING ART IN NARRATIVE THERAPY: ENHANCING THERAPEUTIC POSSIBILITIES  

Microsoft Academic Search

Narrative therapy attempts to help families “reauthor” their lives through a process of externalization, unique outcomes, and performance before an audience. The interventions in this model are accomplished mostly through language. This may make narrative therapy a complicated process for many therapists and clients. The purpose of this article is to show how applying art therapy techniques to the basic

Thomas D. Carlson

1997-01-01

364

Using Art in Narrative Therapy: Enhancing Therapeutic Possibilities.  

ERIC Educational Resources Information Center

Shows how applying art-therapy techniques to the basic principles of narrative therapy enhances the potential for therapists and families to open the door to externalizing conversations that lead to a new life. (Author/MKA)

Carlson, Thomas D.

1997-01-01

365

Therapeutic Actions of Melatonin in Cancer: Possible Mechanisms  

Microsoft Academic Search

Melatonin is a phylogenetically well-preserved molecule with diverse physiological functions. In addition to its well-known regulatory control of the sleep\\/wake cycle, as well as circadian rhythms generally, melatonin is involved in immunomodulation, hematopoiesis, and antioxidative processes. Recent human and animal studies have now shown that melatonin also has important oncostatic properties. Both at physiological and pharmacological doses melatonin exerts growth

Venkataramanujan Srinivasan; D Warren Spence; Seithikurippu R. Pandi-Perumal; Ilya Trakht; Daniel P. Cardinali

2008-01-01

366

Nelfinavir, an HIV-1 Protease Inhibitor, Induces Oxidative Stress–Mediated, Caspase-Independent Apoptosis in Leishmania Amastigotes  

PubMed Central

Background Visceral leishmaniasis has now emerged as an important opportunistic disease in patients coinfected with human immunodeficiency virus type-1 (HIV-1). Although the effectiveness of HIV-1 protease inhibitors, such as nelfinavir, in antiretroviral therapies is well documented, little is known of the impact of these drugs on Leishmania in coinfected individuals. Methodology and Principal Findings Here, we show that nelfinavir generates oxidative stress in the parasite, leading to altered physiological parameters such as an increase in the sub-G1 DNA content, nuclear DNA fragmentation and loss of mitochondrial potential, which are all characteristics of apoptosis. Pretreatment of axenic amastigotes with the caspase inhibitor z-VAD-fmk did not inhibit the increase in sub-G1 DNA content in nelfinavir-treated parasites, suggesting therefore that this antiviral agent does not kill Leishmania amastigotes in a caspase-dependent manner. Furthermore, we observed that the mitochondrial resident protein endonuclease G is involved. We also demonstrate that parasites overexpressing GSH1 (the rate limiting enzyme of glutathione biosynthesis) were more resistant to nelfinavir when compared to untransfected controls. Conclusions and Significance These data suggest that nelfinavir induces oxidative stress in Leishmania amastigotes, culminating in caspase-independent apoptosis, in which DNA is degraded by endonuclease G. This study provides a rationale for future, long-term design of new therapeutic strategies to test nelfinavir as a potential antileishmanial agent as well as for possible future use in Leishmania/HIV-1 coinfections. PMID:20361030

Kumar, Pranav; Lodge, Robert; Trudel, Nathalie; Ouellet, Michel; Ouellette, Marc; Tremblay, Michel J.

2010-01-01

367

HIV-1 transcription and latency: an update  

PubMed Central

Combination antiretroviral therapy, despite being potent and life-prolonging, is not curative and does not eradicate HIV-1 infection since interruption of treatment inevitably results in a rapid rebound of viremia. Reactivation of latently infected cells harboring transcriptionally silent but replication-competent proviruses is a potential source of persistent residual viremia in cART-treated patients. Although multiple reservoirs may exist, the persistence of resting CD4+ T cells carrying a latent infection represents a major barrier to eradication. In this review, we will discuss the latest reports on the molecular mechanisms that may regulate HIV-1 latency at the transcriptional level, including transcriptional interference, the role of cellular factors, chromatin organization and epigenetic modifications, the viral Tat trans-activator and its cellular cofactors. Since latency mechanisms may also operate at the post-transcriptional level, we will consider inhibition of nuclear RNA export and inhibition of translation by microRNAs as potential barriers to HIV-1 gene expression. Finally, we will review the therapeutic approaches and clinical studies aimed at achieving either a sterilizing cure or a functional cure of HIV-1 infection, with a special emphasis on the most recent pharmacological strategies to reactivate the latent viruses and decrease the pool of viral reservoirs. PMID:23803414

2013-01-01

368

Intestinal parasitic infections in human immunodeficiency virus (HIV)-positive and HIV-negative individuals in San Pedro Sula, Honduras.  

PubMed

Honduras has at least five-times more human immunodeficiency virus (HIV)-infected individuals than any other country in Central America. The relationship between HIV status and the presence of intestinal parasites in this part of the world is unknown. This study presents the results from a prospective, comparative study for the presence of parasites in 52 HIV-positive and 48 HIV-negative persons in San Pedro Sula, Honduras. Infection with HIV was determined by microagglutination and confirmed by Western blot analysis. Parasites were detected in stools using formalin-ether concentration, and Kinyoun and trichrome staining. Age, sex, and clinical state of HIV infection were recorded for each study participant. Our results indicate that Cryptosporidium parvum and Strongyloides stercoralis, which are intracellular or live in the mucosa, were found exclusively in persons infected with HIV. In comparison, the prevalence of the extracellular parasites Giardia lamblia, Ascaris lumbricoides, and Trichuris trichiura was significantly higher (P < 0.05) in persons who were HIV-negative. Trichuris worms are in contact with the gut epithelium and less so with the mucosa, whereas Strongyloides lives within the gut mucosa. It is possible that changes in the gut epithelium due to HIV infection do not affect the mucosa and therefore would not affect Strongyloides. We conclude that infection with HIV may selectively deter the establishment of certain intestinal parasites. This may be due to the fact that HIV-induced enteropathy does not favor the establishment of extracellular parasites. Intracellular and mucosal dwelling organisms, however, may benefit from pathologic changes and reduced local immune responses induced by the virus, which, in turn, may lead to higher prevalence among HIV-infected individuals. PMID:9574787

Lindo, J F; Dubon, J M; Ager, A L; de Gourville, E M; Solo-Gabriele, H; Klaskala, W I; Baum, M K; Palmer, C J

1998-04-01

369

Purinergic Receptors are Required for HIV-1 Infection of Primary Human Macrophages  

PubMed Central

Macrophages play a significant role in HIV infection, viral rebound, and in the development of AIDS. However, the function of host proteins in viral replication is incompletely characterized in macrophages. Purinergic receptors, P2X and P2Y, are major components of the macrophage immune response to pathogens, inflammation and cellular damage. We demonstrate that these receptors are necessary for HIV infection of primary human macrophages. Inhibition of purinergic receptors results in a significant reduction in HIV replication in macrophages. This inhibition is independent of viral strain and is dose dependent. We also identify that P2X1, P2X7 and P2Y1 receptors are involved in viral replication. We show that P2X1, but not P2X7 or P2Y1, is necessary for HIV entry into macrophages. We demonstrate that interaction of the HIV surface protein gp120 with macrophages stimulates an increase in ATP release. Thus, we propose that HIV’s binding to macrophages triggers a local release of ATP that stimulates purinergic receptors and facilitates HIV entry and subsequent stages of viral replication. Our data implicate a novel role for a family of host proteins in HIV replication in macrophages and suggest new therapeutic targets to reduce the devastating consequences of HIV infection and AIDS. PMID:22450808

Hazleton, Joy E.; Berman, Joan W.; Eugenin, Eliseo A.

2012-01-01

370

Genetic determinants of pediatric HIV-1 infection: vertical transmission and disease progression among children.  

PubMed

It is very likely that perinatal human immunodeficiency virus type 1 (HIV-1) infection is influenced by a combination of virologic and host factors. A greater understanding of the role played by various risk factors for HIV-1 infection is crucial for the design of new preventive and therapeutic strategies. In recent years, a number of studies have suggested that host genetic factors are important determinants of both the susceptibility to perinatal HIV-1 infection and the subsequent pathogenesis of acquired immunodeficiency syndrome (AIDS). Control of HIV-1 infection involves the processing of specific viral peptides and their presentation to cells of the immune system by highly polymorphic human leukocyte antigen (HLA) alleles. The contribution of multiple HLA class I and II alleles in modulating pediatric HIV/AIDS outcomes has now been confirmed by several independent groups. Penetration of HIV-1 into cells is mediated by interaction between CD4 and chemokine receptors that serve as entry coreceptors. Genetic polymorphisms in chemokine ligand and chemokine receptor genes have recently been associated both with mother-to-child HIV-1 transmission and disease progression in children. These observations suggest a key role for genetic factors in pediatric HIV-1 infection. This article describes the current state of knowledge regarding host genetic influences on pediatric HIV-1 infection and discusses the role of these genes in HIV/AIDS pathogenesis. PMID:11778647

Matt, C; Roger, M

2001-09-01

371

Macrophage Resistance to HIV-1 Infection Is Enhanced by the Neuropeptides VIP and PACAP.  

PubMed

It is well established that host factors can modulate HIV-1 replication in macrophages, critical cells in the pathogenesis of HIV-1 infection due to their ability to continuously produce virus. The neuropeptides VIP and PACAP induce well-characterized effects on macrophages through binding to the G protein-coupled receptors VPAC1, VPAC2 and PAC1, but their influence on HIV-1 production by these cells has not been established. Here, we describe that VIP and PACAP reduce macrophage production of HIV-1, acting in a synergistic or additive manner to decrease viral growth. Using receptor antagonists, we detected that the HIV-1 inhibition promoted by VIP is dependent on its ligation to VPAC1/2, whereas PACAP decreases HIV-1 growth via activation of the VPAC1/2 and PAC1 receptors. Specific agonists of VPAC2 or PAC1 decrease macrophage production of HIV-1, whereas sole activation of VPAC1 enhances viral growth. However, the combination of specific agonists mimicking the receptor preference of the natural neuropeptides reproduces the ability of VIP and PACAP to increase macrophage resistance to HIV-1 replication. VIP and PACAP up-regulated macrophage secretion of the ?-chemokines CCL3 and CCL5 and the cytokine IL-10, whose neutralization reversed the neuropeptide-induced inhibition of HIV-1 replication. Our results suggest that VIP and PACAP and the receptors VPAC2 and PAC1 could be used as targets for developing alternative therapeutic strategies for HIV-1 infection. PMID:23818986

Temerozo, Jairo R; Joaquim, Rafael; Regis, Eduardo G; Savino, Wilson; Bou-Habib, Dumith Chequer

2013-01-01

372

Genetic determinants of pediatric HIV-1 infection: vertical transmission and disease progression among children.  

PubMed Central

It is very likely that perinatal human immunodeficiency virus type 1 (HIV-1) infection is influenced by a combination of virologic and host factors. A greater understanding of the role played by various risk factors for HIV-1 infection is crucial for the design of new preventive and therapeutic strategies. In recent years, a number of studies have suggested that host genetic factors are important determinants of both the susceptibility to perinatal HIV-1 infection and the subsequent pathogenesis of acquired immunodeficiency syndrome (AIDS). Control of HIV-1 infection involves the processing of specific viral peptides and their presentation to cells of the immune system by highly polymorphic human leukocyte antigen (HLA) alleles. The contribution of multiple HLA class I and II alleles in modulating pediatric HIV/AIDS outcomes has now been confirmed by several independent groups. Penetration of HIV-1 into cells is mediated by interaction between CD4 and chemokine receptors that serve as entry coreceptors. Genetic polymorphisms in chemokine ligand and chemokine receptor genes have recently been associated both with mother-to-child HIV-1 transmission and disease progression in children. These observations suggest a key role for genetic factors in pediatric HIV-1 infection. This article describes the current state of knowledge regarding host genetic influences on pediatric HIV-1 infection and discusses the role of these genes in HIV/AIDS pathogenesis. PMID:11778647

Matt, C.; Roger, M.

2001-01-01

373

Multi-branched peptides based on the HIV-1 V3 loop consensus motif inhibit HIV-1 and HIV-2 infection in CD4+ and CD4- cells.  

PubMed

The V3 loop is an hypervariable region of the HIV-1 surface envelope glycoprotein gp120 that is able to generate neutralizing antibodies. These antibodies are generally type-specific. They inhibit the interaction between the V3 loop and the membrane molecules involved in virus-cell and cell-cell fusion. Synthetic peptides based on the V3 loop sequence have been tentatively used to block the fusion process, but the results were unsuccessful. In this report, we confirm that monomeric V3 peptides are devoid of any anti-HIV activity. However, we found that, when assembled in a synthetic polymeric construction (SPC), these peptides have been able to inhibit the infection of human CD4+ lymphocytes and macrophages as well as CD4- epithelial intestinal cells by distantly related isolates of HIV-1 and HIV-2. V3 SPCs, based on the consensus HIV-1 sequence, may therefore represent a new class of therapeutically useful anti-HIV agents able to neutralize a wide range of viral isolates in both CD4+ and CD4- susceptible cells. PMID:7916261

Fantini, J; Yahi, N; Mabrouk, K; Van Rietschoten, J; Rochat, H; Sabatier, J M

1993-11-01

374

Modeling an HIV Particle  

NSDL National Science Digital Library

This activity helps learners visualize the Human Immunodeficiency Virus (HIV) by constructing three-dimensional HIV particle models from paper. The model to be used is a 20-sided polyhedron (icosahedron) and represents a complete viral particle. Learners combine their finished models into one mass. This is a first step toward estimating how many HIV particles could be contained inside a white blood cell before being released into the blood stream to attack new cells.

Gregory L. Vogt, Ed.D.

2011-01-01

375

Neuromuscular complications in HIV  

Microsoft Academic Search

HIV affects many organs of the body, including the nervous system. As a result, a series of neurologic complications have\\u000a created challenges for scientists and clinicians alike. Among these, HIV-associated neuropathy and myopathy may occur at all\\u000a stages of the disease process. Of the neuropathies, distal symmetrical polyneuropathy is the most common form. The pathogenesis\\u000a of primary HIV neuropathy is

Susama Verma; Elena Micsa; Lydia Estanislao; David Simpson

2004-01-01

376

Maternal HIV disclosure to HIV-uninfected children in rural South Africa: a pilot study of a family-based intervention  

PubMed Central

Background As access to treatment increases, large numbers of HIV-positive parents are raising HIV-negative children. Maternal HIV disclosure has been shown to have benefits for mothers and children, however, disclosure rates remain low with between 30-45% of mothers reporting HIV disclosure to their children in both observational and intervention studies. Disclosure of HIV status by parent to an HIV-uninfected child is a complex and challenging psychological and social process. No intervention studies have been designed and tested in Southern Africa to support HIV-positive parents to disclose their status, despite this region being one of the most heavily affected by the HIV epidemic. Method This paper describes the development of a family-centred, structured intervention to support mothers to disclose their HIV status to their HIV-negative school-aged children in rural South Africa, an area with high HIV prevalence. The intervention package includes printed materials, therapeutic tools and child-friendly activities and games to support age-appropriate maternal HIV disclosure, and has three main aims: (1) to benefit family relationships by increasing maternal HIV disclosure; (2) to increase children’s knowledge about HIV and health; (3) to improve the quality of custody planning for children with HIV-positive mothers. We provide the theoretical framework for the intervention design and report the results of a small pilot study undertaken to test its acceptability in the local context. Results The intervention was piloted with 24 Zulu families, all mothers were HIV-positive and had an HIV-negative child aged 6–9 years. Lay counsellors delivered the six session intervention over a six to eight week period. Qualitative data were collected on the acceptability, feasibility and the effectiveness of the intervention in increasing disclosure, health promotion and custody planning. All mothers disclosed something to their children: 11/24 disclosed fully using the words "HIV" while 13/24 disclosed partially using the word "virus". Conclusion The pilot study found the intervention was feasible and acceptable to mothers and counsellors, and provides preliminary evidence that participation in the intervention encouraged disclosure and health promotion. The pilot methodology and small sample size has limitations and further research is required to test the potential of this intervention. A larger demonstration project with 300 families is currently underway. PMID:23418933

2013-01-01

377

Possible sensations  

E-print Network

This thesis explores the sensory human experience through the study of facial expression and non-verbal vocal articulation in hopes of better understanding the range of modes of communications possible both interpersonally ...

Shin, Yae Jin

2013-01-01

378

Chemoenzymatic Syntheses and Anti-HIV-1 Activity of Glucose-Nucleoside Conjugates as Prodrugs  

PubMed Central

Phosphodiester linked conjugates of various nucleosides such as d4U, d4T, IdUrd, ddI, ddA, virazole, ara-A and ara-C containing a glucosyl moiety have been described. These compounds were designed to act as prodrugs, where the corresponding 5?-monophosphates may be generated intracellularly. The synthesis of the glycoconjugates was achieved in good yields by condensation of a glucosyl phosphoramidite 7 with nucleosides in the presence of an activating agent. It was demonstrated that the glucose-conjugates improve water solubility of the nucleoside analogues, for example up to 31-fold for ara-A conjugate compared to ara-A alone. The new conjugates were tested for their anti-HIV-1 activity in human lymphocytes. These derivatives offer a convenient design for potential prodrug candidates with the possibility to improve the physicochemical properties and therapeutic activity of nucleoside analogues. PMID:21077659

Rodríguez-Pérez, Tatiana; Fernández, Susana; Sanghvi, Yogesh S.; Detorio, Mervi; Schinazi, Raymond F.; Gotor, Vicente; Ferrero, Miguel

2010-01-01

379

Primary HIV infection (image)  

MedlinePLUS

HIV (human immunodeficiency virus) is more frequently transmitted through unprotected sex or sharing contaminated needles. Transmission from mother to fetus or through blood products has significantly declined in ...

380

Heme Oxygenase-1 Dysregulation in the Brain: Implications for HIV-Associated Neurocognitive Disorders  

PubMed Central

Heme oxygenase-1 (HO-1) is a highly inducible and ubiquitous cellular enzyme that subserves cytoprotective responses to toxic insults, including inflammation and oxidative stress. In neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease and multiple sclerosis, HO-1 expression is increased, presumably reflecting an endogenous neuroprotective response against ongoing cellular injury. In contrast, we have found that in human immunodeficiency virus (HIV) infection of the brain, which is also associated with inflammation, oxidative stress and neurodegeneration, HO-1 expression is decreased, likely reflecting a unique role for HO-1 deficiency in neurodegeneration pathways activated by HIV infection. We have also shown that HO-1 expression is significantly suppressed by HIV replication in cultured macrophages which represent the primary cellular reservoir for HIV in the brain. HO-1 deficiency is associated with release of neurotoxic levels of glutamate from both HIV-infected and immune-activated macrophages; this glutamate-mediated neurotoxicity is suppressed by pharmacological induction of HO-1 expression in the macrophages. Thus, HO-1 induction could be a therapeutic strategy for neuroprotection against HIV infection and other neuroinflammatory brain diseases. Here, we review various stimuli and signaling pathways regulating HO-1 expression in macrophages, which could promote neuronal survival through HO-1-modulation of endogenous antioxidant and immune modulatory pathways, thus limiting the oxidative stress that can promote HIV disease progression in the CNS. The use of pharmacological inducers of endogenous HO-1 expression as potential adjunctive neuroprotective therapeutics in HIV infection is also discussed. PMID:24862327

Ambegaokar, Surendra S; Kolson, Dennis L

2014-01-01

381

Drug-induced reactivation of apoptosis abrogates HIV-1 infection.  

PubMed

HIV-1 blocks apoptosis, programmed cell death, an innate defense of cells against viral invasion. However, apoptosis can be selectively reactivated in HIV-infected cells by chemical agents that interfere with HIV-1 gene expression. We studied two globally used medicines, the topical antifungal ciclopirox and the iron chelator deferiprone, for their effect on apoptosis in HIV-infected H9 cells and in peripheral blood mononuclear cells infected with clinical HIV-1 isolates. Both medicines activated apoptosis preferentially in HIV-infected cells, suggesting that the drugs mediate escape from the viral suppression of defensive apoptosis. In infected H9 cells, ciclopirox and deferiprone enhanced mitochondrial membrane depolarization, initiating the intrinsic pathway of apoptosis to execution, as evidenced by caspase-3 activation, poly(ADP-ribose) polymerase proteolysis, DNA degradation, and apoptotic cell morphology. In isolate-infected peripheral blood mononuclear cells, ciclopirox collapsed HIV-1 production to the limit of viral protein and RNA detection. Despite prolonged monotherapy, ciclopirox did not elicit breakthrough. No viral re-emergence was observed even 12 weeks after drug cessation, suggesting elimination of the proviral reservoir. Tests in mice predictive for cytotoxicity to human epithelia did not detect tissue damage or activation of apoptosis at a ciclopirox concentration that exceeded by orders of magnitude the concentration causing death of infected cells. We infer that ciclopirox and deferiprone act via therapeutic reclamation of apoptotic proficiency (TRAP) in HIV-infected cells and trigger their preferential elimination. Perturbations in viral protein expression suggest that the antiretroviral activity of both drugs stems from their ability to inhibit hydroxylation of cellular proteins essential for apoptosis and for viral infection, exemplified by eIF5A. Our findings identify ciclopirox and deferiprone as prototypes of selectively cytocidal antivirals that eliminate viral infection by destroying infected cells. A drug-based drug discovery program, based on these compounds, is warranted to determine the potential of such agents in clinical trials of HIV-infected patients. PMID:24086341

Hanauske-Abel, Hartmut M; Saxena, Deepti; Palumbo, Paul E; Hanauske, Axel-Rainer; Luchessi, Augusto D; Cambiaghi, Tavane D; Hoque, Mainul; Spino, Michael; D'Alliessi Gandolfi, Darlene; Heller, Debra S; Singh, Sukhwinder; Park, Myung Hee; Cracchiolo, Bernadette M; Tricta, Fernando; Connelly, John; Popowicz, Anthony M; Cone, Richard A; Holland, Bart; Pe'ery, Tsafi; Mathews, Michael B

2013-01-01

382

Drug-Induced Reactivation of Apoptosis Abrogates HIV-1 Infection  

PubMed Central

HIV-1 blocks apoptosis, programmed cell death, an innate defense of cells against viral invasion. However, apoptosis can be selectively reactivated in HIV-infected cells by chemical agents that interfere with HIV-1 gene expression. We studied two globally used medicines, the topical antifungal ciclopirox and the iron chelator deferiprone, for their effect on apoptosis in HIV-infected H9 cells and in peripheral blood mononuclear cells infected with clinical HIV-1 isolates. Both medicines activated apoptosis preferentially in HIV-infected cells, suggesting that the drugs mediate escape from the viral suppression of defensive apoptosis. In infected H9 cells, ciclopirox and deferiprone enhanced mitochondrial membrane depolarization, initiating the intrinsic pathway of apoptosis to execution, as evidenced by caspase-3 activation, poly(ADP-ribose) polymerase proteolysis, DNA degradation, and apoptotic cell morphology. In isolate-infected peripheral blood mononuclear cells, ciclopirox collapsed HIV-1 production to the limit of viral protein and RNA detection. Despite prolonged monotherapy, ciclopirox did not elicit breakthrough. No viral re-emergence was observed even 12 weeks after drug cessation, suggesting elimination of the proviral reservoir. Tests in mice predictive for cytotoxicity to human epithelia did not detect tissue damage or activation of apoptosis at a ciclopirox concentration that exceeded by orders of magnitude the concentration causing death of infected cells. We infer that ciclopirox and deferiprone act via therapeutic reclamation of apoptotic proficiency (TRAP) in HIV-infected cells and trigger their preferential elimination. Perturbations in viral protein expression suggest that the antiretroviral activity of both drugs stems from their ability to inhibit hydroxylation of cellular proteins essential for apoptosis and for viral infection, exemplified by eIF5A. Our findings identify ciclopirox and deferiprone as prototypes of selectively cytocidal antivirals that eliminate viral infection by destroying infected cells. A drug-based drug discovery program, based on these compounds, is warranted to determine the potential of such agents in clinical trials of HIV-infected patients. PMID:24086341

Hanauske-Abel, Hartmut M.; Saxena, Deepti; Palumbo, Paul E.; Hanauske, Axel-Rainer; Luchessi, Augusto D.; Cambiaghi, Tavane D.; Hoque, Mainul; Spino, Michael; Gandolfi, Darlene D'Alliessi; Heller, Debra S.; Singh, Sukhwinder; Park, Myung Hee; Cracchiolo, Bernadette M.; Tricta, Fernando; Connelly, John; Popowicz, Anthony M.; Cone, Richard A.; Holland, Bart; Pe’ery, Tsafi; Mathews, Michael B.

2013-01-01

383

HIV-associated neurocognitive disorders (HAND).  

PubMed

Neurocognitive impairment still occurs in the era of HAART, though its onset appears to be delayed and its severity reduced, while HIV-infected individuals live longer with the infection. HAND defines three categories of disorders according to standardized measures of dysfunction: asymptomatic neurocognitive impairment (ANI), mild neurocognitive disorder (MND), and HIV-associated dementia (HAD). The pathogenic mechanisms underlying HAND involve host and virus characterizations and interactions and seem to depend heavily on the overall condition of the immune system. Since there are insufficient data at this point to determine the best therapeutic approach, and since HAART apparently is not sufficient to prevent or reverse HAND, therapy with a combination of drugs with high CPE should be considered while adjunctive and alternative therapies are being explored. PMID:25739180

Elbirt, Daniel; Mahlab-Guri, Keren; Bezalel-Rosenberg, Shira; Gill, Harpreet; Attali, Malka; Asher, Ilan

2015-01-01

384

How Do You Get HIV or AIDS?  

MedlinePLUS

... Translate Text Size Print How Do You Get HIV or AIDS? How Do You Get HIV? Certain body fluids from an HIV-infected person ... CDCâ??s HIV Basics: HIV Transmission . HOW is hiv spread? Approximately 50,000 new HIV infections occur ...

385

Visceral leishmaniasis with HIV co-infection and cervical lymphadenopathy  

PubMed Central

Visceral leishmaniasis (VL) is prevalent worldwide. In the past there has been steep rise in the incidence of VL in southern Europe and Africa. Factors attributed for this are economic development, a shift of the reservoir of Leishmania, immunodeficiency due to HIV infection and intravenous drug abuse. The co-infection of VL and HIV is common in southern European—African countries and is proposed that it should be included as an AIDS-defining illness. VL is not only considered to be an opportunistic infection in HIV-infected individuals but it may also reactivate latent infection. This case is worth reporting as it highlights increasing incidence of VL-HIV co-infection and its sparse literature from India, changing ecology and possible evolving epidemic in the Indian subcontinent. Additionally an atypical presentation such as lymphadenopathy in VL should arouse suspicion of HIV co-infection and vice versa. PMID:23576652

Mishra, Sanjay; Shukla, Ayush; Tripathi, Anil Kumar; Kumar, Ashutosh

2013-01-01

386

Development of parallel scales to measure HIV-related stigma.  

PubMed

HIV-related stigma is a multidimensional concept which has pervasive effects on the lives of HIV-infected people as well as serious consequences for the management of HIV/AIDS. In this research three parallel stigma scales were developed to assess personal views of stigma, stigma attributed to others, and internalised stigma experienced by HIV-infected individuals. The stigma scales were administered in two samples: a community sample of 1,077 respondents and 317 HIV-infected pregnant women recruited at clinics from the same community in Tshwane (South Africa). A two-factor structure referring to moral judgment and interpersonal distancing was confirmed across scales and sample groups. The internal consistency of the scales was acceptable and evidence of validity is reported. Parallel scales to assess and compare different perspectives of stigma provide opportunities for research aimed at understanding stigma, assessing the consequences or evaluating possible interventions aimed at reducing stigma. PMID:18266101

Visser, Maretha J; Kershaw, Trace; Makin, Jennifer D; Forsyth, Brian W C

2008-09-01

387

HERV-K-specific T cells eliminate diverse HIV-1/2 and SIV primary isolates.  

PubMed

The genetic diversity of HIV-1 represents a major challenge in vaccine development. In this study, we establish a rationale for eliminating HIV-1-infected cells by targeting cellular immune responses against stable human endogenous retroviral (HERV) antigens. HERV DNA sequences in the human genome represent the remnants of ancient infectious retroviruses. We show that the infection of CD4+ T cells with HIV-1 resulted in transcription of the HML-2 lineage of HERV type K [HERV-K(HML-2)] and the expression of Gag and Env proteins. HERV-K(HML-2)-specific CD8+ T cells obtained from HIV-1-infected human subjects responded to HIV-1-infected cells in a Vif-dependent manner in vitro. Consistent with the proposed mode of action, a HERV-K(HML-2)-specific CD8+ T cell clone exhibited comprehensive elimination of cells infected with a panel of globally diverse HIV-1, HIV-2, and SIV isolates in vitro. We identified a second T cell response that exhibited cross-reactivity between homologous HIV-1-Pol and HERV-K(HML-2)-Pol determinants, raising the possibility that homology between HIV-1 and HERVs plays a role in shaping, and perhaps enhancing, the T cell response to HIV-1. This justifies the consideration of HERV-K(HML-2)-specific and cross-reactive T cell responses in the natural control of HIV-1 infection and for exploring HERV-K(HML-2)-targeted HIV-1 vaccines and immunotherapeutics. PMID:23143309

Jones, R Brad; Garrison, Keith E; Mujib, Shariq; Mihajlovic, Vesna; Aidarus, Nasra; Hunter, Diana V; Martin, Eric; John, Vivek M; Zhan, Wei; Faruk, Nabil F; Gyenes, Gabor; Sheppard, Neil C; Priumboom-Brees, Ingrid M; Goodwin, David A; Chen, Lianchun; Rieger, Melanie; Muscat-King, Sophie; Loudon, Peter T; Stanley, Cole; Holditch, Sara J; Wong, Jessica C; Clayton, Kiera; Duan, Erick; Song, Haihan; Xu, Yang; SenGupta, Devi; Tandon, Ravi; Sacha, Jonah B; Brockman, Mark A; Benko, Erika; Kovacs, Colin; Nixon, Douglas F; Ostrowski, Mario A

2012-12-01

388

Mismatched double-stranded RNA (polyI-polyC 12U) is synergistic with multiple anti-HIV drugs and is active against drug-sensitive and drug-resistant HIV1 in vitro  

Microsoft Academic Search

Although highly active anti-retroviral therapy (HAART) is successful in the treatment of HIV infection, problems with toxicity, drug-resistant variants, and therapeutic failures have compromised the long-term utility of existing combination regimens. Mismatched double-stranded RNA (polyI-polyC12U) is an immune modulator with inherent anti-HIV activity. Cell toxicities and anti-HIV activities of fourteen anti-HIV agents were determined alone and in combination with polyI-polyC12U.

Robert J Essey; Brenda R McDougall; W. Edward Robinson

2001-01-01

389

HIV-1 Diversity, Drug-Resistant Mutations, and Viral Evolution among High-Risk Individuals in Phase II HIV Vaccine Trial Sites in Southern China  

PubMed Central

HIV-1 prevalence in Guangxi, China, has been growing since 1996, when the first case was reported. Over half of HIV-1 positive patients in Guangxi Province were injecting drug users (IDUs), possibly because of the province’s location near drug-trafficking routes. Since a phase II HIV vaccine trial is ongoing there, a current characterization of the subtypes of HIV-1 among IDUs in Guangxi would provide critical information for future HIV vaccine trials, as well as further control and prevention of HIV-1 transmission. Thus, we conducted a molecular epidemiological investigation of HIV-1 samples from 2008–2010 among IDUs in multiple cities in Guangxi Province. Our results, based on the gag/pol fragment, indicated a very high proportion (78.47%) of HIV-1 CRF08_BC recombinants, some CRF01_AE (15.38%) recombinants, and a low proportion of CRF07_BC (6.15%) recombinants among the IDUs. The high proportion of CRF08 HIV-1 strains among recent IDUs matches the vaccine candidate constructs. However, future vaccine development should also incorporate CRF01-targeted vaccine candidates. Distinct Env sequence evolution patterns were observed for CRF08_BC and CRF01_AE, indicating that different local selection pressures have been exerted on these two HIV-1 subtypes. Unique drug-resistant mutations were also detected, and our data indicate that HIV treatment programs should consider pre-existing drug-resistant mutations. PMID:23869225

Qi, Haiyan; Zhao, Ke; Xu, Fei; Zhang, Xuzhao; Zhang, Zhiyong; Yang, Li; Li, Chunling; Liang, Xu; Guo, Weigui; Chen, Shihai; Liu, Zhihao; Zhang, Wenyan; Yu, Xiao-Fang

2013-01-01

390

[Bad breath: causes, diagnostic and therapeutic practice].  

PubMed

Bad breath (BB) can be noted in various diseases of oral cavity, nasopharynx, upper gastrointestinal tract divisions (foetor ex ore) or be felt in expired air (halitosis) in various bronchopulmonary diseases, renal or hepatic failure, and diabetic ketoacidosis. BB requires interaction between different specialists making it possible to find the cause of this clinical symptom and the optimal therapeutic approach. PMID:17419361

Sheptulin, A A

2007-01-01

391

Genetic analyses of HIV-1 pol sequences from Zimbabwean patients.  

PubMed

This study analysed the sequence of HIV-1 pol gene derived from Zimbabwean infected patients. Sequence analysis, performed on 8 samples, revealed that sequences were classified as subtype C (n=5), subtype B (n=2) and CRF01_AE (n=1). Two patients, treated with a therapeutic regimen containing NRTI/NNRTI, harboured drug resistance mutations in HIV-1 DNA. Phylogenetic analysis performed on subtype C sequences showed that our strains were aggregated in different clusters depending on the country of origin. PMID:25180853

Falasca, Francesca; Temperoni, Chiara; Mazzuti, Laura; Lo Presti, Alessandra; Ciccozzi, Massimo; Di Filippo, Elisa; Iaiani, Giancarlo; Taliani, Gloria; Turriziani, Ombretta

2014-07-01

392

HCV versus HIV drug discovery: Déjŕ vu all over again?  

PubMed

Efforts to address HIV infection have been highly successful, enabling chronic suppression of viral replication with once-daily regimens. More recent research into HCV therapeutics have also resulted in very promising clinical candidates. This Digest explores similarities and differences in the two fields and compares the chronology of drug discovery relative to the availability of enabling tools, and concludes that safe and convenient, once-daily regimens are likely to reach approval much more rapidly for HCV than was the case for HIV. PMID:23489621

Watkins, William J; Desai, Manoj C

2013-04-15

393

Inhibitory effect of aqueous dandelion extract on HIV-1 replication and reverse transcriptase activity  

PubMed Central

Background Acquired immunodeficiency syndrome (AIDS), which is caused by the human immunodeficiency virus (HIV), is an immunosuppressive disease that results in life-threatening opportunistic infections. The general problems in current therapy include the constant emergence of drug-resistant HIV strains, adverse side effects and the unavailability of treatments in developing countries. Natural products from herbs with the abilities to inhibit HIV-1 life cycle at different stages, have served as excellent sources of new anti-HIV-1 drugs. In this study, we aimed to investigate the anti-HIV-1 activity of aqueous dandelion extract. Methods The pseudotyped HIV-1 virus has been utilized to explore the anti-HIV-1 activity of dandelion, the level of HIV-1 replication was assessed by the percentage of GFP-positive cells. The inhibitory effect of the dandelion extract on reverse transcriptase activity was assessed by the reverse transcriptase assay kit. Results Compared to control values obtained from cells infected without treatment, the level of HIV-1 replication and reverse transcriptase activity were decreased in a dose-dependent manner. The data suggest that dandelion extract has a potent inhibitory activity against HIV-1 replication and reverse transcriptase activity. The identification of HIV-1 antiviral compounds from Taraxacum officinale should be pursued. Conclusions The dandelion extract showed strong activity against HIV-1 RT and inhibited both the HIV-1 vector and the hybrid-MoMuLV/MoMuSV retrovirus replication. These findings provide additional support for the potential therapeutic efficacy of Taraxacum officinale. Extracts from this plant may be regarded as another starting point for the development of an antiretroviral therapy with fewer side effects. PMID:22078030

2011-01-01

394

Pancreatic Pseudocyst: Therapeutic Dilemma  

PubMed Central

Pancreatic pseudocyst develops in both acute and chronic pancreatitis. It is an entity likely to either remain asymptomatic or develop devastating complications. Despite being diagnosed easily, treatment exercise is still at crossroads whether in the form of internal or external drainage or endoscopic, laparoscopic, or open intervention with a good radiological guidance. The therapeutic dilemma whether to treat a patient with a pancreatic pseudocyst, as well as when and with what technique, is a difficult one. This paper is intended to get information about diagnostic and therapeutic exercises most appropriate for acute and chronic pancreatic pseudocyst. PMID:22577595

Khanna, A. K.; Tiwary, Satyendra K.; Kumar, Puneet

2012-01-01

395

Therapeutic Antioxidant Medical Gas  

PubMed Central

Medical gases are pharmaceutical gaseous molecules which offer solutions to medical needs and include traditional gases, such as oxygen and nitrous oxide, as well as gases with recently discovered roles as biological messenger molecules, such as carbon monoxide, nitric oxide and hydrogen sulphide. Medical gas therapy is a relatively unexplored field of medicine; however, a recent increasing in the number of publications on medical gas therapies clearly indicate that there are significant opportunities for use of gases as therapeutic tools for a variety of disease conditions. In this article, we review the recent advances in research on medical gases with antioxidant properties and discuss their clinical applications and therapeutic properties. PMID:19177183

Nakao, Atsunori; Sugimoto, Ryujiro; Billiar, Timothy R; McCurry, Kenneth R

2009-01-01

396

DELIVERY OF THERAPEUTIC PROTEINS  

PubMed Central

The safety and efficacy of protein therapeutics are limited by three interrelated pharmaceutical issues, in vitro and in vivo instability, immunogenicity and shorter half-lives. Novel drug modifications for overcoming these issues are under investigation and include covalent attachment of poly(ethylene glycol) (PEG), polysialic acid, or glycolic acid, as well as developing new formulations containing nanoparticulate or colloidal systems (e.g. liposomes, polymeric microspheres, polymeric nanoparticles). Such strategies have the potential to develop as next generation protein therapeutics. This review includes a general discussion on these delivery approaches. PMID:20049941

Pisal, Dipak S.; Kosloski, Matthew P.; Balu-Iyer, Sathy V.

2009-01-01

397

Cardiac effects in perinatally HIV-infected and HIV-exposed but uninfected children and adolescents: a view from the United States of America  

PubMed Central

Introduction Human immunodeficiency virus (HIV) infection is a primary cause of acquired heart disease, particularly of accelerated atherosclerosis, symptomatic heart failure, and pulmonary arterial hypertension. Cardiac complications often occur in late-stage HIV infections as prolonged viral infection is becoming more relevant as longevity improves. Thus, multi-agent HIV therapies that help sustain life may also increase the risk of cardiovascular events and accelerated atherosclerosis. Discussion Before highly active antiretroviral therapy (HAART), the two-to-five-year incidence of symptomatic heart failure ranged from 4 to 28% in HIV patients. Patients both before and after HAART also frequently have asymptomatic abnormalities in cardiovascular structure. Echocardiographic measurements indicate left ventricular (LV) systolic dysfunction in 18%, LV hypertrophy in 6.5%, and left atrial dilation in 40% of patients followed on HAART therapy. Diastolic dysfunction is also common in long-term survivors of HIV infection. Accelerated atherosclerosis has been found in HIV-infected young adults and children without traditional coronary risk factors. Infective endocarditis, although rare in children, has high mortality in late-stage AIDS patients with poor nutritional status and severely compromised immune systems. Although lymphomas have been found in HIV-infected children, the incidence is low and cardiac malignancy is rare. Rates of congenital cardiovascular malformations range from 5.6 to 8.9% in cohorts of HIV-uninfected and HIV-infected children with HIV-infected mothers. In non-HIV-infected infants born to HIV-infected mothers, foetal exposure to ART is associated with reduced LV dimension, LV mass, and septal wall thickness and with higher LV fractional shortening and contractility during the first two years of life. Conclusions Routine, systematic, and comprehensive cardiac evaluation, including a thorough history and directed laboratory assays, is essential for the care of HIV-infected adults and children as cardiovascular illness has become a part of care for long-term survivors of HIV infection. The history should include traditional risk factors for atherosclerosis, prior opportunistic infections, environmental exposures, and therapeutic and illicit drug use. Laboratory tests should include a lipid profile, fasting glucose, and HIV viral load. Asymptomatic cardiac disease related to HIV can be fatal, and secondary effects of HIV infection often disguise cardiac symptoms, so systematic echocardiographic monitoring is warranted. PMID:23782480

Lipshultz, Steven E; Miller, Tracie L; Wilkinson, James D; Scott, Gwendolyn B; Somarriba, Gabriel; Cochran, Thomas R; Fisher, Stacy D

2013-01-01

398

Safe Thinking and Affect Regulation (STAR): Human Immunodeficiency Virus Prevention in Alternative/Therapeutic Schools  

ERIC Educational Resources Information Center

Objective: To evaluate the effectiveness of Safe Thinking and Affect Regulation (STAR), a 14-session HIV-prevention program for adolescents at alternative/therapeutic schools. Because these youth frequently have difficulties with emotions and cognitions, it was designed to improve sexuality-specific affect management and cognitive monitoring, as…

Brown, Larry K.; Nugent, Nicole R.; Houck, Christopher D.; Lescano, Celia M.; Whiteley, Laura B.; Barker, David; Viau, Lisa; Zlotnick, Caron

2011-01-01

399

HIV and malnutrition: effects on immune system.  

PubMed

HIV or human immunodeficiency virus infection has assumed worldwide proportions and importance in just a span of 25 years. Continuous research is being done in many parts of the world regarding its treatment and vaccine development, and a lot of money has flown into this. However, fully understanding the mechanisms of immune depletion has still not been possible. The focus has also been on improving the quality of life of people living with HIV/AIDS through education, counselling, and nutritional support. Malnutrition further reduces the capacity of the body to fight this infection by compromising various immune parameters. Knowledge of essential components of nutrition and incorporating them in the management goes a long way in improving quality of life and better survival in HIV-infected patients. PMID:22242039

Duggal, Shalini; Chugh, Tulsi Das; Duggal, Ashish Kumar

2012-01-01

400

[New therapeutic trends in AIDS].  

PubMed

In this paper we describe the current status of the chemotherapy of HIV-related disease, and the newly emerging approaches to this problem. Azidothymidine, the first anti-HIV drug, is now used by thousands of patients with AIDS, and is able to induce a substantial improvement of their clinical status. However, due to its toxicity and its very limited activity against HIV replication in chronically infected cells (the natural reservoir of the virus in the body), it is crucial that new drugs be developed. A number of compounds belonging to the dideoxynucleoside family (the same of AZT) have been synthesized and used in HIV-infected patients, with promising results. Nevertheless, new compounds with different mechanisms of action, and with excellent anti-HIV efficacy need to be developed, particularly those that can inhibit the late stages of HIV replication. This will permit a polychemotherapeutic approach against HIV infection that, as in the case of anticancer chemotherapy, has conceivably better chances to be effective in patients with HIV-related disease. PMID:1314726

Perno, C F; Caliň, R

1992-02-01

401

HIV and Communication  

ERIC Educational Resources Information Center

The human immunodeficiency virus (HIV) continues to plague many countries across the globe, including the United States, Africa, China and India. Children and adults have been infected with HIV, and both populations can present with communication disorders that coexist with the presence of the virus. The purpose of this paper is to present an…

McNeilly, L.G.

2005-01-01

402

HIV and fertility revisited  

Microsoft Academic Search

Young (2005) argues that HIV related population declines reinforced by the fertility response to the epidemic will lead to higher capital–labor ratios and to higher per capita incomes in the affected countries of Africa. Using household level data on fertility from South Africa and relying on between cohort variations in country level HIV infection, he estimates a large negative effect

Sebnem Kalemli-Ozcan; Belgi Turan

2011-01-01

403

HIV and Fertility Revisited  

Microsoft Academic Search

Young (2005) argues that HIV related population declines reinforced by the fertility response to the epidemic will lead to higher capital-labor ratios and to higher per capita incomes in the affected countries of Africa. Using household level data on fertility from South Africa and relying on between cohort variation in country level HIV infection, he estimates a large negative effect

Sebnem Kalemli-Ozcan; Belgi Turan

2010-01-01

404

Positive: HIV Affirmative Counseling.  

ERIC Educational Resources Information Center

At the end of the 1980s, counselors largely lacked an integrated approach to counseling people living with HIV disease. This book describes the experience of counseling this group of persons. The major premise here is that counselors who counsel HIV-positive clients must come to understand and affirm their clients' experiences. The text defines a…

Kain, Craig D.

405

Pregnancy and HIV  

MedlinePLUS

... 611 Pregnancy and HIV HOW DO BABIES GET AIDS? HOW CAN WE PREVENT INFECTION OF NEWBORNS? BREAST FEEDING HOW DO WE KNOW IF A ... BABIES GET AIDS? HIV, the virus that causes AIDS, can be transmitted from an infected mother to her newborn child. According to the World Health Organization, without ...

406

Living with HIV/AIDS  

MedlinePLUS

Infection with HIV is serious. But the outlook for people with HIV/AIDS is improving. If you are infected with HIV, there are many things you can do to ... health care provider who knows how to treat HIV. You may want to join a support group. ...

407

HIV Discrimination and the Health of Women Living with HIV  

Microsoft Academic Search

Women living with HIV are especially vulnerable to discrimination because of the stigma associated with the disease, as well as their race, gender and class status. To investigate the association between self-reported HIV discrimination and health outcomes among African-American and white women living with HIV, 366 women living with HIV were recruited from HIV\\/AIDS clinics in Georgia and Alabama. In

Gina M. Wingood; Ralph J. DiClemente; Isis Mikhail; Donna Hubbard McCree; Susan L. Davies; James W. Hardin; Shani Harris Peterson; Edward W. Hook; Mike Saag

2007-01-01

408

HIV preferentially infects HIV-specific CD4+ T cells  

Microsoft Academic Search

HIV infection is associated with the progressive loss of CD4+ T cells through their destruction or decreased production. A central, yet unresolved issue of HIV disease is the mechanism for this loss, and in particular whether HIV-specific CD4+ T cells are preferentially affected. Here we show that HIV-specific memory CD4+ T cells in infected individuals contain more HIV viral DNA

Daniel C. Douek; Jason M. Brenchley; Michael R. Betts; David R. Ambrozak; Brenna J. Hill; Yukari Okamoto; Joseph P. Casazza; Janaki Kuruppu; Kevin Kunstman; Steven Wolinsky; Zvi Grossman; Mark Dybul; Annette Oxenius; David A. Price; Mark Connors; Richard A. Koup

2002-01-01

409

Inhibition of HIV by an anti-HIV protease synthetic peptide blocks an early step of viral replication.  

PubMed

The processing of the human immunodeficiency virus (HIV) gag and gag-pol precursor proteins by the virus-encoded protease is an essential step in maturation of infectious virus particles. Like most retroviral proteases, the HIV protease belongs to the aspartyl-protease family and can be inhibited by specific inhibitors. Twenty-four synthetic peptides known to be inhibitors of human renin were tested for inhibition of HIV replication in tissue cultures. One of them, a synthetic peptide analogue, SR41476, which has been shown to be a specific inhibitor of purified recombinant HIV1 protease in vitro, totally blocked infection with different isolates including the HIV1 LAV prototype, the highly cytopathic Zairian isolate HIV1 NDK, and HIV2 ROD, both in primary blood lymphocytes (PBL) and in the lymphoid cell lines MT4 and CEM, for at least 3 weeks. It also significantly reduced virus replication in chronically infected CEM cells, without any effect on cell proliferation. Radioimmunoprecipitation assay revealed that the inhibitor blocked processing of polyprotein precursors p55 gag and p40 gag into a mature form of gag proteins, p25 and p18. Synthetic peptide analogue SR 41476, when added before infection, efficiently inhibited formation of HIV DNA provirus and successfully suppressed synthesis of HIV-specific proteins. These results imply that the HIV protease inhibitor not only inhibited virus maturation in the late phase of the HIV replication cycle, but also interfered in the early phase, before the provirus was formed. This mechanism of antiviral activity provides new possibilities and strategies for AIDS chemotherapy. PMID:1480823

Venaud, S; Yahi, N; Fehrentz, J L; Guettari, N; Nisato, D; Hirsch, I; Chermann, J C

1992-01-01

410

HIV-1 diversity versus HLA class I polymorphism.  

PubMed

HIV-1 is rapidly diversifying in African, Asian and Caucasoid populations, which in parallel display extensive polymorphism of genes encoding class I human leukocyte antigens (HLA). Immune responses mediated by HLA class I molecules are imprinting mutations in HIV-1, which in turn affects HIV-1 diversity. Intra- and inter-ethnic studies have shown reproducible HLA class I allele, haplotype and supertype associations with HIV-1 infection and the development of AIDS (HIV/AIDS). In Caucasoids and Africans, HLA-B57 and related alleles of the B58 supertype associate with low viraemia, delayed onset of AIDS and, possibly, cytotoxic T lymphocyte (CTL)-driven attenuation of HIV-1. In HIV-1-exposed but uninfected Southeast Asians, HLA-A11 has been associated with CTL responses directed against HIV-1 Nef. HLA-A11 displays unique peptide-binding properties and is recognized by natural killer cells utilizing the inhibitory killer Ig-like receptor 3DL2 in a peptide-dependent manner. PMID:15629408

Stephens, Henry A F

2005-01-01

411

Transverse myelitis and acute HIV infection: a case report  

PubMed Central

Background Most HIV infected patients will develop some sort of neurologic involvement of the disease throughout their lives, usually in advanced stages. Neurologic symptoms may occur in acute HIV infection but myelopathy in this setting is rare. Up until this date, only two cases of transverse myelitis as a manifestation of acute HIV infection have been reported in the literature. Therapeutic approach in these patients is not well defined. Case presentation A 35 year-old male Caucasian recently returned from the tropics presented to our hospital with urinary retention and acute paraparesis. After extensive diagnostic workup he was diagnosed with acute HIV infection presenting as transverse myelitis. Full neurologic recovery was observed without the use of anti-retroviral therapy. Conclusion Acute spinal cord disorders are challenging, as they present a wide array of differential diagnosis and may lead to devastating sequelae. Timely and rigorous diagnostic workup is of the utmost importance when managing these cases. Clinicians should be aware of the protean manifestations of acute HIV infection, including central nervous system involvement, and have a low threshold for HIV screening. PMID:24646059

2014-01-01

412

HIV-1, human interaction database: current status and new features.  

PubMed

The 'Human Immunodeficiency Virus Type 1 (HIV-1), Human Interaction Database', available through the National Library of Medicine at http://www.ncbi.nlm.nih.gov/genome/viruses/retroviruses/hiv-1/interactions, serves the scientific community exploring the discovery of novel HIV vaccine candidates and therapeutic targets. Each HIV-1 human protein interaction can be retrieved without restriction by web-based downloads and ftp protocols and includes: Reference Sequence (RefSeq) protein accession numbers, National Center for Biotechnology Information Gene identification numbers, brief descriptions of the interactions, searchable keywords for interactions and PubMed identification numbers (PMIDs) of journal articles describing the interactions. In addition to specific HIV-1 protein-human protein interactions, included are interaction effects upon HIV-1 replication resulting when individual human gene expression is blocked using siRNA. A total of 3142 human genes are described participating in 12,786 protein-protein interactions, along with 1316 replication interactions described for each of 1250 human genes identified using small interfering RNA (siRNA). Together the data identifies 4006 human genes involved in 14,102 interactions. With the inclusion of siRNA interactions we introduce a redesigned web interface to enhance viewing, filtering and downloading of the combined data set. PMID:25378338

Ako-Adjei, Danso; Fu, William; Wallin, Craig; Katz, Kenneth S; Song, Guangfeng; Darji, Dakshesh; Brister, J Rodney; Ptak, Roger G; Pruitt, Kim D

2015-01-01

413

Antiviral Stratagems Against HIV-1 Using RNA Interference (RNAi) Technology  

PubMed Central

The versatility of human immunodeficiency virus (HIV)-1 and its evolutionary potential to elude antiretroviral agents by mutating may be its most invincible weapon. Viruses, including HIV, in order to adapt and survive in their environment evolve at extremely fast rates. Given that conventional approaches which have been applied against HIV have failed, novel and more promising approaches must be employed. Recent studies advocate RNA interference (RNAi) as a promising therapeutic tool against HIV. In this regard, targeting multiple HIV sites in the context of a combinatorial RNAi-based approach may efficiently stop viral propagation at an early stage. Moreover, large high-throughput RNAi screens are widely used in the fields of drug development and reverse genetics. Computer-based algorithms, bioinformatics, and biostatistical approaches have been employed in traditional medicinal chemistry discovery protocols for low molecular weight compounds. However, the diversity and complexity of RNAi screens cannot be efficiently addressed by these outdated approaches. Herein, a series of novel workflows for both wet- and dry-lab strategies are presented in an effort to provide an updated review of state-of-the-art RNAi technologies, which may enable adequate progress in the fight against the HIV-1 virus. PMID:23761954

Vlachakis, Dimitrios; Tsiliki, Georgia; Pavlopoulou, Athanasia; Roubelakis, Maria G.; Champeris Tsaniras, Spyridon; Kossida, Sophia

2013-01-01

414

Antiviral Stratagems Against HIV-1 Using RNA Interference (RNAi) Technology.  

PubMed

The versatility of human immunodeficiency virus (HIV)-1 and its evolutionary potential to elude antiretroviral agents by mutating may be its most invincible weapon. Viruses, including HIV, in order to adapt and survive in their environment evolve at extremely fast rates. Given that conventional approaches which have been applied against HIV have failed, novel and more promising approaches must be employed. Recent studies advocate RNA interference (RNAi) as a promising therapeutic tool against HIV. In this regard, targeting multiple HIV sites in the context of a combinatorial RNAi-based approach may efficiently stop viral propagation at an early stage. Moreover, large high-throughput RNAi screens are widely used in the fields of drug development and reverse genetics. Computer-based algorithms, bioinformatics, and biostatistical approaches have been employed in traditional medicinal chemistry discovery protocols for low molecular weight compounds. However, the diversity and complexity of RNAi screens cannot be efficiently addressed by these outdated approaches. Herein, a series of novel workflows for both wet- and dry-lab strategies are presented in an effort to provide an updated review of state-of-the-art RNAi technologies, which may enable adequate progress in the fight against the HIV-1 virus. PMID:23761954

Vlachakis, Dimitrios; Tsiliki, Georgia; Pavlopoulou, Athanasia; Roubelakis, Maria G; Tsaniras, Spyridon Champeris; Kossida, Sophia

2013-01-01

415

HIV-1, human interaction database: current status and new features  

PubMed Central

The ‘Human Immunodeficiency Virus Type 1 (HIV-1), Human Interaction Database’, available through the National Library of Medicine at http://www.ncbi.nlm.nih.gov/genome/viruses/retroviruses/hiv-1/interactions, serves the scientific community exploring the discovery of novel HIV vaccine candidates and therapeutic targets. Each HIV-1 human protein interaction can be retrieved without restriction by web-based downloads and ftp protocols and includes: Reference Sequence (RefSeq) protein accession numbers, National Center for Biotechnology Information Gene identification numbers, brief descriptions of the interactions, searchable keywords for interactions and PubMed identification numbers (PMIDs) of journal articles describing the interactions. In addition to specific HIV-1 protein–human protein interactions, included are interaction effects upon HIV-1 replication resulting when individual human gene expression is blocked using siRNA. A total of 3142 human genes are described participating in 12 786 protein–protein interactions, along with 1316 replication interactions described for each of 1250 human genes identified using small interfering RNA (siRNA). Together the data identifies 4006 human genes involved in 14 102 interactions. With the inclusion of siRNA interactions we introduce a redesigned web interface to enhance viewing, filtering and downloading of the combined data set. PMID:25378338

Ako-Adjei, Danso; Fu, William; Wallin, Craig; Katz, Kenneth S.; Song, Guangfeng; Darji, Dakshesh; Brister, J. Rodney; Ptak, Roger G.; Pruitt, Kim D.

2015-01-01

416

Predictors of sustained therapeutic change  

Microsoft Academic Search

The authors integrate explorations by Blatt and colleagues of contributions of patient personality, therapeutic relationship, and change in mental representation to sustained therapeutic change. A pretreatment personality characteristic, self-critical perfectionism, a negative self-schema, significantly interfered with therapeutic progress in manual-directed, brief outpatient treatment for depression. The therapeutic relationship, however, facilitated changes in this negative self-representation, leading to sustained therapeutic change.

Sidney J. Blatt; David C. Zuroff; Lance L. Hawley; John S. Auerbach

2010-01-01

417

Clinical Management of HIV Drug Resistance  

PubMed Central

Combination antiretroviral therapy for HIV-1 infection has resulted in profound reductions in viremia and is associated with marked improvements in morbidity and mortality. Therapy is not curative, however, and prolonged therapy is complicated by drug toxicity and the emergence of drug resistance. Management of clinical drug resistance requires in depth evaluation, and includes extensive history, physical examination and laboratory studies. Appropriate use of resistance testing provides valuable information useful in constructing regimens for treatment-experienced individuals with viremia during therapy. This review outlines the emergence of drug resistance in vivo, and describes clinical evaluation and therapeutic options of the individual with rebound viremia during therapy. PMID:21994737

Cortez, Karoll J.; Maldarelli, Frank

2011-01-01

418

Infant feeding and HIV.  

PubMed

Mother-to-child HIV transmission is the main cause of HIV infection in children. About two thirds of children infected vertically are infected during pregnancy and around the time of delivery, while the remainder are infected during breast-feeding. Although breast-feeding tends to be the best way to feed infants, substituting breast-feeding can reduce the risk of mother-to-child HIV transmission when mothers are HIV-seropositive. However, when breast milk substitutes are used, infants are 5 times more likely to have bacterial infections than are breast-fed infants, even in the context of good hygiene. Where hygiene is poor, artificially fed infants may be 20 times more likely to die from diarrhea than are breast-fed infants. HIV-positive women need information on the risks and benefits of breast-feeding and of the various alternatives, and support in deciding which method is best. Infant feeding options are discussed. PMID:12294837

1998-01-01

419

New concepts in therapeutic photomedicine: photochemistry, optical targeting and the therapeutic window  

SciTech Connect

Advances in optics technology, synthetic photochemistry, and the science of photobiology make it possible to think beyond phototherapy and photochemotherapy which is dependent on direct photochemical alteration of metabolites or direct phototoxic insult to cells. This report discusses another gender of photomedicine therapy which includes in vivo photoactivation of medicines, photon-dependent drug delivery, and manipulation of host and exposure source to maximize therapeutic index. These therapeutic manipulations are made possible because the skin is highly overperfused and because non-ionizing electromagnetic radiation that enters skin and blood has adequate photon energy to cause electronic excitation. Radiation of 320-800 nm is not very directly phototoxic, is absorbed by a variety of relatively nontoxic photolabile molecules and has an internal dosimetric depth profile. This radiation can therefore be used to activate, deactivate, bind, release or biotransform medications in vivo in skin or other organs. The photochemist, synthetic chemist and photobiologist can collaborate to significantly increase therapeutic possibilities.

Parrish, J.A.

1981-07-01

420

Therapeutic Recombinant Monoclonal Antibodies  

ERIC Educational Resources Information Center

During the last two decades, the rapid growth of biotechnology-derived techniques has led to a myriad of therapeutic recombinant monoclonal antibodies with significant clinical benefits. Recombinant monoclonal antibodies can be obtained from a number of natural sources such as animal cell cultures using recombinant DNA engineering. In contrast to…

Bakhtiar, Ray

2012-01-01

421

AMUM LECTURE: Therapeutic ultrasound  

Microsoft Academic Search

The use of ultrasound in medicine is now quite commonplace, especially with the recent introduction of small, portable and relatively inexpensive, hand-held diagnostic imaging devices. Moreover, ultrasound has expanded beyond the imaging realm, with methods and applications extending to novel therapeutic and surgical uses. These applications broadly include: tissue ablation, acoustocautery, lipoplasty, site-specific and ultrasound mediated drug activity, extracorporeal lithotripsy,

Lawrence A. Crum

2004-01-01

422

Therapeutic Human Papillomavirus Vaccination  

Microsoft Academic Search

Despite impressive progress in prevention and therapy of premalignant and malignant dysplasia the worldwide burden of cancer is relatively unchanged. Supplementation of the therapeutic arsenal by immunotherapeutic methods would have the potential to make a significant impact. Dysplastic lesions and cancer of the cervix show strong association with human papillomaviruses (HPV), as do tumours of other mucosal epithelia like squamous

Andreas E. Albers; Andreas M. Kaufmann

2009-01-01

423

Controversies in therapeutic touch  

Microsoft Academic Search

One of the most puzzling areas covered under the umbrella of integrative medicine is the field of energy healing. Based on the notion of a subtle vital force which is presumed to be the source of health, many ancient healing techniques have been evolved within this paradigm, including the modern American variant called Therapeutic Touch (TT). This article reviews the

Eric Leskowitz

2003-01-01

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The epidemiology of HIV infection in Morocco: systematic review and data synthesis  

PubMed Central

Summary Morocco has made significant strides in building its HIV research capacity. Based on a wealth of empirical data, the objective of this study was to conduct a comprehensive and systematic literature review and analytical synthesis of HIV epidemiological evidence in this country. Data were retrieved using three major sources of literature and data. HIV transmission dynamics were found to be focused in high-risk populations, with female sex workers (FSWs) an