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J Med Chem. 2000 Oct 5;43(20):3799-802.
6-Aminoquinolones as new potential anti-HIV agents.

Cecchetti V, Parolin C, Moro S, Pecere T, Filipponi E, Calistri A, Tabarrini O, Gatto B, Palumbo M, Fravolini A, Palu' G.

Dipartimento di Chimica e Tecnologia del Farmaco, University of Perugia, Via del Liceo 1, 06123 Perugia, Italy.

A series of 6-aminoquinolone compounds were evaluated for their in vitro activity against human immunodeficiency virus type 1 (HIV-1). Compound 12a, bearing a methyl substituent at the N-1 position and a 4-(2-pyridyl)-1-piperazine moiety at the C-7 position, was the most active in inhibiting HIV-1 replication on de novo infected C8166 human lymphoblastoid cell lines. The 12a EC(50) value was 0.1 microM, a 7-20-fold lower concentration relative to that for compounds 8a and 7a containing a cyclopropyl and tert-butyl substituent at the N-1 position, respectively. When the C-6 amino group was replaced with a fluorine atom, a decreased antiviral effect was observed. The observed effects are selective, since potency is substantially reduced when testing the compounds against the herpes simplex virus type 1 (HSV-1). Active quinolone derivatives very efficiently interact with TAR RNA, which suggests a nucleic acid-targeted mechanism of action.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11020296&dopt=Abstract

Fertil Steril. 2000 Oct;74(4):753-9.
Quantitative analysis of estrogen receptor alpha and beta messenger ribonucleic acid levels in normal endometrium and ovarian endometriotic cysts using a real-time reverse transcription-polymerase chain reaction assay.

Matsuzaki S, Uehara S, Murakami T, Fujiwara J, Funato T, Okamura K.

Department of Obstetrics and Gynecology, Tohoku University School of Medicine, Sendai, Japan. matsuzakb-gy.med.tohoku.ac.jp

OBJECTIVE: To quantify messenger RNA (mRNA) levels of the two estrogen receptor isoforms, estrogen receptor-alpha (ER-alpha) and estrogen receptor-beta (ER-beta) in the eutopic endometrium and ovarian endometriotic cysts. DESIGN: Prospective study. SETTING: University hospital. PATIENT(S): Patients with endometriosis and patients with uterine leiomyoma or carcinoma in situ. INTERVENTION(S): Gonadotropin-releasing hormone agonist (GnRH-a)-treated (n = 12) or untreated (n = 24) endometriotic cysts were obtained from 36 patients during laparoscopic cystectomy. Eutopic endometrium tissues were obtained from 24 patients during or immediately after surgery. MAIN OUTCOME MEASURE(S): ER-alpha and ER-beta mRNA levels, using a real-time reverse transcription (RT)-polymerase chain reaction (PCR) assay, TaqMan RT-PCR. RESULT(S): Eutopic endometrium and ovarian endometriotic cysts showed predominantly higher levels of ER-alpha mRNA than ER-beta mRNA. Although ER-alpha and ER-beta mRNA levels in the eutopic endometrium were affected by a cyclic change in ovarian hormones, ovarian endometriotic cysts were less affected. Moreover, a long-term hypoestrogenic state induced by GnRH-a especially decreased ER-alpha mRNA levels in endometriotic cysts. Consequently, the relative ratios of ER-alpha to ER-beta mRNA levels in both GnRH-a-treated and untreated endometriotic cysts were significantly lower than those in the eutopic endometrium. CONCLUSION(S): The results suggest that the principal and regulatory effects of estrogens may be mediated mainly via ER-alpha rather than ER-beta in both the eutopic endometrium and endometriotic cysts.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11020519&dopt=Abstract

Hepatogastroenterology. 2000 Jul-Aug;47(34):1072-6.
Interferon-alpha treatment of children with chronic hepatitis D virus infection: the Greek experience.

Dalekos GN, Galanakis E, Zervou E, Tzoufi M, Lapatsanis PD, Tsianos EV.

Department of Internal Medicine, Pediatrics Medical School, University of Ioannina, Greece.

BACKGROUND/AIMS: The therapeutic experience of interferon-alpha therapy against hepatitis D virus infection in affected children is rather limited. For this reason, we conducted a retrospective study (duration: 1991-1995) in order to evaluate the efficacy and the safety of interferon-alpha in children suffering from chronic hepatitis D in Northwestern Greece. METHODOLOGY: Seven children who were found to be infected with HDV in a total of 324 children seropositive for hepatitis B virus infection during the 5-year period of the study were treated with interferon-alpha, 3 x 10(6) U/m2 body surface area, intramuscularly or subcutaneously, 3 times weekly for 1 year (after an informed consent obtained from their parents). Patients were assessed monthly by hematological serological and biochemical tests. Clinical progress, levels of serum alanine aminotransferase, hepatitis D ribonucleic acid (HDV-RNA) and hepatitis B deoxyribonucleic acid (HBV-DNA), seroconversion of hepatitis B surface antigen (HBsAg) and Hepatitis Be Antigen (HBeAg) and liver histology were used as response criteria. RESULTS: Posttreatment alanine transferase levels were significantly reduced (P < 0.05) but Immunoglobulin M and total anti-hepatitis D virus (anti-HDV) antibodies remained positive in all, while hepatitis D ribonucleic acid persisted positive in 4 cases. In addition, no seroconversion of HBsAg or HBeAg was noted and the liver histology progress was disappointing. Side effects including mild fever, arthralgias and malaise and reversible neutropenia and thrombocytopenia were common, but not particularly disturbing. Nevertheless, the children remained fully active on treatment, felt well and attended school. Initially 4 children had been below the 10th percentile for weight and height. All thrived during treatment and two crossed above the 10th percentile indicating height velocity and body mass index increase. CONCLUSIONS: The administration of regular interferon-alpha doses for treating children with chronic hepatitis D was safe as attested by the mild side effects and the objective clinical criteria regarding their growth, but relatively ineffective. Although the prevalence of hepatitis D virus infection is now generally decreased, this study indirectly indicates that more effective agents and new approaches at the molecular level of the hepatitis D virus genome are urgently warranted for its control in individuals already infected with the virus. Finally, the poor therapeutic results in the present study further enhance the necessity of the expanded vaccination against Hepatitis B virus according to the World Health Organization's recommendations.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11020882&dopt=Abstract

Neurol Med Chir (Tokyo). 2000 Sep;40(9):463-6.
Fatal severe vasospasm due to rewarming following hypothermia--case report.

Jimbo H, Dohi K, Nakamura Y, Izumiyama H, Ikeda Y, Matsumoto K, Kushima M, Takaki A.

Department of Neurosurgery, Showa University School of Medicine, Tokyo.

A 37-year-old female died of cerebral vasospasm as a complication of rewarming following hypothermia therapy for severe head injury. She presented with severe consciousness disturbance and anisocoria after falling down a flight of stairs. Computed tomography (CT) revealed a right acute subdural hematoma and temporal contusion. Following surgery, mild hypothermia was started and rewarming was completed by the 11th day. Neurological examination showed no abnormalities, but intracranial pressure (ICP) suddenly increased and she manifested anisocoria on the 13th day. Repeat CT revealed a low density area in the right middle cerebral artery region and cerebral angiography showed diffuse narrowing of the main arterial trunks. A cerebrospinal fluid (CSF) sample was collected using an intraventricular ICP monitoring catheter. The CSF level of 8-hydroxy-2'-deoxyguanosine was elevated during the rewarming period, indicating substantial deoxyribonucleic acid (DNA) oxidation. She died on the 15th day due to uncontrollable ICP. Histological examination at autopsy of the narrowed artery found the waving phenomenon in the internal elastic lamina and invasion of inflammatory cells into the adventitia. These findings constitute the possible evidence that free-radical-mediated oxidative DNA damage may be important in the genesis of severe vasospasm due to rewarming following hypothermia.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11021078&dopt=Abstract

Biopolymers. 2002 Dec 15;65(6):424-35.
Molecular dynamics simulation studies of induced fit and conformational capture in U1A-RNA binding: do molecular substates code for specificity?

Pitici F, Beveridge DL, Baranger AM.

Chemistry Department and Molecular Biophysics Program, Wesleyan University, Middletown, CT 06459, USA.

Molecular dynamics (MD) simulations on stem loop 2 of U1 small nuclear RNA and a construct of the U1A protein were carried out to obtain predictions of the structures for the unbound forms in solution and to elucidate dynamical aspects of induced fit upon binding. A crystal structure of the complex between the U1A protein and stem loop 2 RNA and an NMR structure for the uncomplexed form of the U1A protein are available from Oubridge et al. (Nature, 1994, Vol. 372, pp. 432-438) and Avis et al. (Journal of Molecular Biology, 1996, Vol. 257, pp. 398-411), respectively. As a consequence, U1A-RNA binding is a particularly attractive case for investigations of induced fit in protein-nucleic acid complexation. When combined with the available structural data, the results from simulations indicate that structural adaptation of U1A protein and RNA define distinct mechanisms for induced fit. For the protein, the calculations indicate that induced fit upon binding involves a non-native thermodynamic substate in which the structure is preorganized for binding. In contrast, induced fit of the RNA involves a distortion of the native structure in solution to an unstable form. However, the RNA solution structures predicted from simulation show evidence that structures in which groups of bases are favorably oriented for binding the U1A protein are thermally accessible. These results, which quantify with computational modeling recent proposals on induced fit and conformational capture by Leuillot and Varani (Biochemistry, 2001, Vol. 40, pp. 7947-7956) and by Williamson (Nature Structural Biology, 2000, Vol. 7, pp. 834-837) suggest an important role for intrinsic molecular architecture and substates other than the native form in the specificity of protein-RNA interactions. 2002 Wiley Periodicals, Inc.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12434430&dopt=Abstract

The average human scalp is covered by approximatey 100,000 hair follicles. Each hair undergoes hair cycle and normally 50-100 hairs randomly fall out a day, which is unnoticeable because lost hair is replaced by as many new hairs springing up daily. Hair loss results from the fall out of hair from the hair follicle. Alopecia or excessive, premature hair loss is the condition caused by many factors. Loss of hair itself does not pose critical health problems because biological role of human hair is relatively marginal. Hair on our scalp protects the head from mechanical shock, heat loss, and exposure to UV-light. The eyelashes and eyebrowes protect the eyes, and hair in the ear canal or the nasal passages help filter out particles and pathogens, thus protecting our internal organs. However, hair does play important social role: it is one of the major determinants of our appearance and identity in daily life. Fullness of hair also implicates or manifests physical integrity and youthfulness of the person. Losing hair could have more than just emotional impacts on individuals. The hair is a unique organ that goes through a characteristic cycle consisting of an immature phase, a growing phase called anagen, a transitional phase between the growing phase and the resting phase called catagen, and finally a resting phase called telogen in which the hair stops growing, waiting to fall out. 85-90% of hairs on our body are in anagen phase or growing phase, which lasts anywhere from two to five years. This phase is followed by a short regression phase, or catagen, which lasts 2-3 weeks. Approximately 1% of hair follicles are in catagen. Approximately 10-15% of hair follicles are in the resting phase, the telogen, which lasts about 3-5 months. Hair follicles typically goes through 10-20 asynchronous cycles during the lifetime. Persistent loss of more than 150 hairs would consist a state of hair loss, or alopecia, albeit it could be temporary.

DHEA is a natural hormone, and it is produced in our body by the adrenal glands. DHEA has been suggested to provide numerous potential benefits. DHEA (or dehydroepiandrosterone) is converted into androgens (male hormones) or estrogens (female hormones) in the cells. Our bodies produce decreasing amount of DHEA as we get older. various health benefits: To deter aging, improve sexual function/erectile dysfunction, treat cognitive decline, enhance athletic performance, facilitate weight loss, improve strength, prevent osteoporosis, enhance immunomodulation for rheumatic conditions, and treat depression.

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