Methanolic extracts from Achyrocline satureioides (Dc.) Lam, Aristolochia macroura Gomez, Lithraea molleoides (Vell.) Engl., Schinus molle L., unlike those from Celtis spinosa Spreng, Chenopodium ambrosioides L., Petiveria alliacea L., and Plantago major L. showed cytotoxic activity against a human hepatocellular carcinoma cell line, Hep G2. Schinus molle L. was the most active (IC50=50+/-7 microg/ml). These results call for further studies of these extracts.

Anacardiaceae↗

PubMed2002

Antiviral activity of Petiveria alliacea against the bovine viral diarrhea virus.

BACKGROUND: Natural products are a relevant source of antiviral drugs. Five medicinal plants used in Argentina have been assayed to detect inhibition of viral growth. METHODS: Antiviral activity of the infusions and methanolic extracts of Aristolochia macroura, Celtis spinosa, Plantago major, Schinus areira, Petiveria alliacea and four extracts obtained from the leaves and stems of the last plant were evaluated by the plaque assay. RESULTS: P. alliacea, unlike A. macroura, C. spinosa, P. major and S. areira, inhibited bovine viral diarrhea virus (BVDV) replication. Neither P. alliacea nor the assays of the other plants were active against herpes simplex virus type 1, poliovirus type 1, adenovirus serotype 7 and vesicular stomatitis virus type 1. Four extracts of P. alliacea were assayed to detect anti-BVDV activity. Ethyl acetate (EC(50) of 25 microg/ml) and dichloromethane (EC(50) of 43 microg/ml) extracts were active; moreover, promising SI (IC(50)/EC(50)) values were obtained. CONCLUSION: BVDV is highly prevalent in the cattle population, there are no antiviral compounds available; additionally, it is a viral model of the hepatitis C virus. For these reasons and in view of the results obtained, the isolation and characterization of the antiviral components present in the P. alliacea extracts is worth carrying out in the future.

Animals↗

PubMed2001

Reconstituted syntaxin1a/SNAP25 interacts with negatively charged lipids as measured by lateral diffusion in planar supported bilayers.

According to the soluble N-ethylmaleimide-sensitive factor (NSF)-attachment protein (SNAP) receptor hypothesis (SNARE hypothesis), interactions between target SNAREs and vesicle SNAREs (t- and v-SNAREs) are required for membrane fusion in intracellular vesicle transport and exocytosis. The precise role of the SNAREs in tethering, docking, and fusion is still disputed. Biophysical measurements of SNARE interactions in planar supported membranes could potentially resolve some of the key questions regarding the mechanism of SNARE-mediated membrane fusion. As a first step toward this goal, recombinant syntaxin1A/SNAP25 (t-SNARE) was reconstituted into polymer-supported planar lipid bilayers. Reconstituted t-SNAREs in supported bilayers bound soluble green fluorescent protein/vesicle-associated membrane protein (v-SNARE), and the SNARE complexes could be specifically dissociated by NSF/alpha-SNAP in the presence of ATP. The physiological activities of SNARE complex formation were thus well reproduced in this reconstituted planar model membrane system. A large fraction (~75%) of the reconstituted t-SNARE was laterally mobile with a lateral diffusion coefficient of 7.5 x 10(-9) cm(2)/s in a phosphatidylcholine lipid background. Negatively charged lipids reduced the mobile fraction of the t-SNARE and the lipids themselves. Phosphatidylinositol-4,5-bisphosphate was more effective than phosphatidylserine in reducing the lateral mobility of the complexes. A model of how acidic lipid-SNARE interactions might alter lipid fluidity is discussed.

Anions↗

PubMed2001

Comparison of Internet and community pharmacies.

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Community Pharmacy Services↗

PubMed2000

Tethered polymer-supported planar lipid bilayers for reconstitution of integral membrane proteins: silane-polyethyleneglycol-lipid as a cushion and covalent linker.

There is increasing interest in supported membranes as models of biological membranes and as a physiological matrix for studying the structure and function of membrane proteins and receptors. A common problem of protein-lipid bilayers that are directly supported on a hydrophilic substrate is nonphysiological interactions of integral membrane proteins with the solid support to the extent that they will not diffuse in the plane of the membrane. To alleviate some of these problems we have developed a new tethered polymer-supported planar lipid bilayer system, which permitted us to reconstitute integral membrane proteins in a laterally mobile form. We have supported lipid bilayers on a newly designed polyethyleneglycol cushion, which provided a soft support and, for increased stability, covalent linkage of the membranes to the supporting quartz or glass substrates. The formation and morphology of the bilayers were followed by total internal reflection and epifluorescence microscopy, and the lateral diffusion of the lipids and proteins in the bilayer was monitored by fluorescence recovery after photobleaching. Uniform bilayers with high lateral lipid diffusion coefficients (0.8-1.2 x 10(-8) cm(2)/s) were observed when the polymer concentration was kept slightly below the mushroom-to-brush transition. Cytochrome b(5) and annexin V were used as first test proteins in this system. When reconstituted in supported bilayers that were directly supported on quartz, both proteins were largely immobile with mobile fractions < 25%. However, two populations of laterally mobile proteins were observed in the polymer-supported bilayers. Approximately 25% of cytochrome b(5) diffused with a diffusion coefficient of approximately 1 x 10(-8) cm(2)/s, and 50-60% diffused with a diffusion coefficient of approximately 2 x 10(-10) cm(2)/s. Similarly, one-third of annexin V diffused with a diffusion coefficient of approximately 3 x 10(-9) cm(2)/s, and two-thirds diffused with a diffusion coefficient of approximately 4 x 10(-10) cm(2)/s. A model for the interaction of these proteins with the underlying polymer is discussed.

Annexin A5↗

PubMed1999

Hepatosplenic cat-scratch disease in children: selected clinical features and treatment.

We reviewed 19 cases of hepatosplenic cat-scratch disease at Texas Children's Hospital (Houston). The range of the patients' ages was 2 years 4 months to 11 years 8 months. The chief complaint was fever for all patients. The duration of fever before diagnosis was 7 to 56 days (mean, 22 days). Abdominal pain was present in 13 patients (68%). Thirteen children were treated with rifampin alone, and three received rifampin therapy plus gentamicin or trimethoprim-sulfamethoxazole. Once rifampin therapy was initiated alone or in combination, improvement was noted within 1 to 5 days (mean, 2.6 days) for patients who had had prolonged fever the duration of which before rifampin therapy averaged 3 weeks. The most common dosage and duration for our patients were 20 mg/[kg x d] every 12 hours and 14 days, respectively. Rifampin should be considered in the initial antimicrobial treatment of hepatosplenic cat-scratch disease.

Animals↗

PubMed1999

Coadministration of phenytoin and felbamate: evidence of additional phenytoin dose-reduction requirements based on pharmacokinetics and tolerability with increasing doses of felbamate.

PURPOSE: This open-label study investigated the pharmacokinetic interaction of phenytoin (PHT) and felbamate (FBM). METHODS: Ten subjects with epilepsy receiving PHT monotherapy were administered increasing doses of FBM (1,200, 1,800, 2,400-3,600 mg/day) at 2-week intervals. PHT doses were reduced by 20% on an individual basis when evidence of clinically significant intolerance was present. With intolerance, the PHT dose was reduced before the next incremental FBM dose. Blood samples were analyzed for FBM, PHT, and PHT metabolite 5-(4-hydroxyphenyl)-5-phenylhydantoin (HPPH). RESULTS: Total PHT plasma concentrations increased with coadministered FBM. PHT Cmax increased from 15.9 microg/ml at baseline to 20.9 microg/ml after 1,200 mg/day FBM and to 26.8 microg/ml after 1,800 mg/day FBM. Four subjects required a 20% PHT dose reduction after 1,800 mg/day FBM and six after the administration of 2,400 mg/day FBM. All subjects required further 20% PHT reductions before 3,600 mg/day FBM. FBM Cmax and AUCT were reduced, and apparent clearance increased compared with data from FBM monotherapy. CONCLUSIONS: With the initiation of FBM therapy in subjects receiving PHT, the PHT dosage should be reduced by 20%. Further PHT dose reductions are likely to be necessary if the FBM dose is increased. The requirements for reductions in dose might be predicted by clinical signs of PHT intolerance.

Adult↗

PubMed1998

Challenges for pediatric radiology using computed radiography.

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Child↗

PubMed1998

Umbilical metastasis (Sister Mary Joseph's nodule) in a child.

Metastatic malignancy to the umbilicus, also known as Sister Mary Joseph's nodule, is a rare condition, which to our knowledge has not been reported in a child. We present a case of an umbilical metastasis from carcinoma of the colon in a boy who was also receiving chemotherapy for mediastinal lymphoblastic lymphoma.

Abdominal Neoplasms↗

PubMed1998

Study of an Argentine mistletoe, the hemiparasite Ligaria cuneifolia (R. et P.) Tiegh. (Loranthaceae).

Ligaria cuneifolia (R. et P.) Tiegh. is an hemiparasite species used in Argentine folk medicine as a substitute for the European mistletoe (Viscum album L.) based on its putative activity of decreasing high blood pressure. This paper analyzes flavonoid composition, protein constituents and the possible immunomodulatory and antitumoral effects of this species. Micromolecular study disclosed quercetin-free, quercetin-glycosylated and proanthocyanidins corresponding to cyanidin monomers, which implies a particular metabolic pathway. Proteins present in L. cuneifolia extracts analyzed by SDS-PAGE presented multiple bands with molecular weights ranging from 14 to 90 kD. These features contribute to the characterization of the native mistletoe. As V. album is being used in cancer treatment due to its immunomodulatory and antitumoral activity, the action of aqueous L. cuneifolia extracts on murine lymphocytes was investigated. Culture of murine spleen cells alone or stimulated with Concanavalin A or lipopolysaccharide in presence of L. cuneifolia extracts indicated a certain stimulation of splenocytes alone and an inhibition of splenocytes stimulated with Concanvalin A or lipopolysaccharide. An inhibitory effect was also observed on the proliferation of murine leukemia cells. In addition, aqueous extracts increased nitric oxide production by murine macrophages. These results suggest that L. cuneifolia extracts exert an immunomodulatory effect on the mouse immune system.

Animals↗

PubMed1998

Pharmacoeconomic analysis of using Sinemet CR over standard Sinemet in parkinsonian patients with motor fluctuations.

OBJECTIVE: To compare the costs of pharmacotherapy in patients with Parkinson's disease before and after converting from standard Sinemet to extended-release Sinemet CR. DESIGN: Investigators retrospectively reviewed records of patients converting from Sinemet to Sinemet CR for efficacy and total drug costs. Cost-effectiveness was evaluated retrospectively from data collected in prospective Sinemet CR efficacy trials. SETTING: Parkinson's disease clinic at a tertiary care university teaching hospital. PATIENTS: 100 patients with motor fluctuations who had undergone an initial 6-month course of Sinemet therapy, followed by a 6-month course of Sinemet CR. MAIN OUTCOME MEASURES: Total cost was measured as the cost of Sinemet formulations plus the costs of other antiparkinson medications. Differences in pre- and postconversion costs were compared by using the paired, two-tailed Student's t-test. A substudy of 39 patients on the cost-effectiveness of conversion measured the ratio of daily medication costs to the daily hours "on" without chorea. RESULTS: While total daily medication costs after conversion increased by 21%, patients experienced either a comparable or an improved degree of disease control with Sinemet CR. Patients who were also taking selegiline were able to decrease selegiline expense by 20%. The costs of other adjunctive medications did not differ significantly after conversion. The cost-effectiveness analysis revealed an increase in postconversion on time by 2.2 hours (p = 0.0001), accompanied by a $2.85 decrease in total cost per hour on without chorea (p = 0.11). CONCLUSIONS: Although Sinemet CR is more costly, it may be more cost-effective in patients with motor fluctuations. Some patients may be able to reduce adjunctive medications.

Adult↗

PubMed1998

Beyond benzodiazepines: alternative pharmacologic agents for the treatment of insomnia.

OBJECTIVE: To review the epidemiology, etiology, and classification of insomnia and provide an overview of the pharmacologic therapy of insomnia. Novel nonbenzodiazepine hypnotics including zolpidem, zopiclone, and zaleplon, as well as nonprescription products such as valerian and melatonin, are reviewed in detail. DATA SOURCES: A MEDLINE search was performed to identify relevant clinical studies, case reports, abstracts, and review articles published between April 1992 and December 1997. Key search terms included insomnia, benzodiazepines, zolpidem, zopiclone, zaleplon, Cl 284,846, melatonin, and valerian. Additional references were obtained from the lists of review articles and textbooks. DATA EXTRACTION AND SYNTHESIS: Data concerning the safety and efficacy of the hypnotic agents were extracted from all available clinical trials and abstracts. Background information regarding insomnia, benzodiazepines, and other hypnotics was extracted from the most current literature, including review articles and textbooks. CONCLUSIONS: New developments in benzodiazepine receptor pharmacology have introduced novel nonbenzodiazepine hypnotics that provide comparable efficacy to benzodiazepines. Although they may possess theoretical advantages over benzodiazepines based on their unique pharmacologic profiles, they offer few, if any, significant advantages in terms of adverse effects. Over-the-counter agents such as valerian and melatonin may be useful in alleviating mild, short-term insomnia, but further clinical trials are required to fully evaluate their safety and efficacy.

Acetamides↗

PubMed1997

Manganese(II) active site mutants of 3,4-dihydroxyphenylacetate 2,3-dioxygenase from Arthrobacter globiformis strain CM-2.

Whereas all other members of the extradiol-cleaving catechol dioxygenase family are iron-dependent, the 3,4-dihydroxyphenylacetate 2,3-dioxygenase (MndD) from Arthrobacter globiformis CM-2 is dependent on manganese for catalytic activity. Recently, the endogenous iron ligands of one family member, the 2,3-dihydroxybiphenyl 1,2-dioxygenase (BphC), were identified crystallographically as two histidines and a glutamic acid [Sugiyama, K., et al. (1995) Proc. Jpn. Acad., Ser. B 71, 32-35; Han, et al. (1995) Science 270, 976-980; Senda, T., et al. (1996) J. Mol. Biol. 255, 735-752]. Though BphC and MndD have low overall sequence identity (23%), the three BphC metal ligands are all conserved in MndD (H155, H214, and E266). In order to determine whether these residues also act as ligands to manganese in MndD, site-directed mutants of each were constructed, purified, and analyzed for activity and metal content. Mutations H155A, H214A, and E266Q yielded purified enzymes with specific activities of <0.1% of that of the wild-type dioxygenase and bound 0.4, 1.8, and 33% of the wild-type level of manganese, respectively. The relatively high level of manganese [with a Mn(II) EPR signal distinctly different from that of the wild-type enzyme] observed for E266Q suggests that the glutamine may act as a weak ligand to the metal. Mutant E266D, which retains the potential metal binding capability of a carboxylate group, exhibited 12% of the wild-type activity in crude extracts, suggesting that Mn remains bound; however, this mutant protein was too unstable to be purified and analyzed for metal content. On the basis of the low activity and metal content of mutant proteins, we propose that the conserved residues H155, H214, and E266 ligate manganese in MndD. As is the case with the superoxide dismutases, the extradiol-cleaving catechol dioxygenases appear to utilize identical coordinating residues for their iron- and manganese-dependent enzymes.

Amino Acid Sequence↗

PubMed1997

The relationship of tinnitus to craniocervical mandibular disorders.

Patients with craniocervical mandibular (TMD) disorders can present with tinnitus as a primary or secondary complaint. The embryology and functional anatomy of the middle ear, temporomandibular joint, muscles of mastication and associated tendons, ligaments, blood vessels, nerves and lymphatics was found to be helpful in establishing etiologic concepts which relate tinnitus to these temporomandibular disorders. In addition to etiologic concepts, treatment modalities are described. The authors relate their experiences as well as those of others with different patient populations.

Female↗