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Pathogen research abs 1 || Pathogen research abs 2 || Pathogen research abs 3 || Pathogen research abs 4 || Pathogen research abs 5 || Hormone and endocrine research abs 1 || Hormone and endocrine research abs 2 || Hormone and endocrine research abs 3 || Hormone and endocrine research abs 4 || Hormone and endocrine research abs 5 || Follicle and follicular cells research abs 1 || Interferon research abs 1 || Hemoglobin research abs || Stem cell research abs || Nucleic acid research abs || Herpes research abs

J Antimicrob Chemother. 2002 Sep;50(3):365-74.
Pharmacokinetic and antiretroviral activity in mice of oral [P(1),P(2)-bis[2-(adenin-9-yl)ethoxymethyl]phosphonate], a prodrug of 9-(2-phosphonylmethoxyethyl)adenine.

Rossi L, Dominici S, Serafini S, Casabianca A, Cerasi A, Chiarantini L, Celeste AG, Cappellacci L, Franchetti P, Grifantini M, Magnani M.

Institute of Biochemistry G. Fornaini and Institute of Hygiene, University of Urbino, 61029 Urbino, Italy.

9-(2-Phosphonylmethoxyethyl)adenine (PMEA) is an antiviral drug with activity against herpes viruses, Epstein-Barr virus and retroviruses, including the human immunodeficiency virus. Unfortunately, oral PMEA administration, as required for long-term therapy, is hindered by its low bioavailability. In the present study, the synthesis, oral bioavailability and antiretroviral activity of a new prodrug of PMEA, consisting of two molecules of PMEA bound together by a P-O-P bond (Bis-PMEA), are reported. Pharmacokinetic experiments in mice showed that the oral bioavailabilities of PMEA following oral gavage of Bis-PMEA or PMEA (at a dose equivalent to 28 mg of PMEA/kg) were 50.8 and 13.5%, respectively. These results correlate with the antiviral efficacy of Bis-PMEA administered orally at a dose equivalent to 50 mg/kg of PMEA in C57 BL/6 mice infected with the retroviral complex LP-BM5. Oral treatment with Bis-PMEA proved to be more effective than oral treatment with PMEA given at equimolar doses. Moreover, oral Bis-PMEA was more effective than intraperitoneal PMEA (50 mg/kg) in reducing lymphoadenopathy, hypergammaglobulinaemia and lymph node proviral DNA content, overall in the first weeks post virus inoculation. Bis-PMEA thus appears to be an efficient oral prodrug of PMEA without significant toxicity, at least in this mouse model.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12205061&dopt=Abstract

Life Sci Space Res. 1971;9:1-9.
Immune states in long-term space flights.

Ginsberg HS.

Department of Microbiology, School of Medicine, University of Pennsylvania, Philadelphia, Penn., USA.

Maintenance of health, as contrasted to illness induced by infectious agents, reflects a tenuous balance between the host's resistance and the number and genetic characteristics of the infectious organisms present. Nature has evolved both nonspecific defense mechanisms and specific immune systems to protect the body against invasion by exogenous organisms or the numerous agents which may reside dormant within the host. Long-term space flights with their accompanying prolonged weightlessness, unaccustomed environmental factors, emotional disturbances, and unforeseen influences may alter the host's natural or specific immune states. The non-specific and specific host defenses will be discussed, and the particular effects which their alteration might have on provocation of latent viral infections will be considered. Viruses which classically may be induced to cause recurrent infections such as herpes simplex and herpes zoster will be described, but in addition the effect that altered host defenses might have on slow virus infections such as kuru and virus-induced malignancies will be emphasized.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12206176&dopt=Abstract

Antiviral Res. 2002 Sep;55(3):447-55.
Antiherpes simplex virus type 2 activity of casuarinin from the bark of Terminalia arjuna Linn.

Cheng HY, Lin CC, Lin TC.

Graduate Institute of Pharmaceutical Science, College of Pharmacy, Kaohsiung Medical University, 100 Shih Chuan 1st Road, Taiwan, ROC.

Casuarinin, a hydrolyzable tannin isolated from the bark of Terminalia arjuna Linn. (Combretaceae), was investigated for its antiviral activity on herpes simplex type 2 (HSV-2) in vitro. Results showed that the IC(50) of casuarinin in XTT and plaque reduction assays were 3.6+/-0.9 and 1.5+/-0.2 microM, respectively. The 50% cytotoxic concentration for cell growth (CC(50)) was 89+/-1 microM. Thus, the selectivity index (SI) (ratio of CC(50) to IC(50)) of casuarinin was 25 and 59 for XTT and plaque reduction assays, respectively. Casuarinin continued to exhibit antiviral activity even added 12 h after infection. During the attachment assay, casuarinin was shown to prevent the attachment of HSV-2 to cells. Furthermore, casuarinin also exhibited an activity in inhibiting the viral penetration. Interestingly, casuarinin was virucidal at a concentration of 25 microM, reducing viral titers up to 100,000-fold. This study concludes that casuarinin possesses anti-herpesvirus activity in inhibiting viral attachment and penetration, and also disturbing the late event(s) of infection.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12206882&dopt=Abstract

Br J Dermatol. 2002 Sep;147(3):563-7.
Multiple Epstein-Barr virus-associated subcutaneous angioleiomyomas in a patient with acquired immunodeficiency syndrome.

Chang JY, Wang S, Hung CC, Tsai TF, Hsiao CH.

Department of Pathology, National Taiwan University Hospital, no. 7 Chung-Shan South Road, Taipei, Taiwan.

Tumours of smooth muscle origin, either solitary or multiple, are occasionally found in immunocompromised patients, particularly in children with acquired immunodeficiency syndrome (AIDS). Most of the reported AIDS-associated leiomyomatous neoplasms have been found in the visceral organs, and the tumour cells all possessed the Epstein-Barr virus (EBV) genome. Here we present a 32-year-old-man with AIDS who developed three skin nodules on his lower left extremity. No other tumorous lesions were found using computed tomography scans. Two of the three nodules were resected for pathological examination. Histologically, both tumours were well circumscribed and located in the subcutis. The tumours were composed of interlacing fascicles of spindle-shaped cells with prominent vasculature and lymphocytic infiltration. No pleomorphism, mitosis or necrosis was seen. Immunohistochemically, the tumour cells were reactive to smooth muscle actin and desmin. Angioleiomyoma was diagnosed. EBV-encoded small RNAs were also demonstrated in the nucleus of the tumour cells by in situ hybridization but no EBV receptor (CD21) or latent membrane protein (LMP)-1 was found in the tumour cells. No human herpesvirus (HHV)-8 genome was detected in the lesion using polymerase chain reaction analysis. The results of this study indicated that EBV containing subcutaneous angioleiomyoma was another neoplasm that must be considered in patients with human immunodeficiency virus infection who develop skin nodules. The role of EBV in the pathogenesis of this unique neoplasm is still unknown.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12207602&dopt=Abstract

J Biol Chem. 2003 Feb 28;278(9):7397-405. Epub 2002 Dec 16.
Latency-associated nuclear antigen of Kaposi's sarcoma-associated herpesvirus functionally interacts with heterochromatin protein 1.

Lim C, Lee D, Seo T, Choi C, Choe J.

Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Korea.

Latency-associated nuclear antigen (LANA) of Kaposi's sarcoma-associated herpesvirus plays an important role in maintenance of the viral genome during latent infection. LANA additionally participates in the transcriptional regulation of several viral and cellular promoters. When tethered to constitutively active promoters, the protein exhibits transcriptional repressor activity. In this report, we further characterized cell type-, promoter-, and domain-specific transcriptional repression by LANA. We additionally speculated on the mechanism underlying transcriptional repression by the C terminus of the protein. Subnuclear localization patterns and association with heterochromatin suggested a possible link between LANA and heterochromatin protein 1, a representative heterochromatin-associated protein. In vivo and in vitro binding and immunofluorescence assays revealed that LANA associates with heterochromatin protein 1 in an isotype-specific manner. Furthermore, biochemical fractionation and transient replication assays supported the possibility that this interaction contributes to transcriptional repression, targeting to subnuclear structures, and latent DNA replication activity of LANA.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12486118&dopt=Abstract

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