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Leukemia. 2003 Aug;17(8):1482-98.
Therapeutic efficacy of prenylation inhibitors in the treatment of myeloid leukemia.

Morgan MA, Ganser A, Reuter CW.

Department of Hematology and Oncology, Hannover Medical School, Hannover, Germany.

Farnesyltransferase inhibitors (FTIs) represent a new class of anticancer agents that specifically target post-translational farnesylation of various proteins that mediate several cellular processes such as signal transduction, growth, differentiation, angiogenesis and apoptosis. These compounds were originally designed to block oncogenic RAS-induced tumor growth by impeding RAS localization to the membrane, but it is now evident that FTIs also affect processing of several other proteins. The need for novel therapies in myeloid leukemia is underscored by the high rate of treatment failure due to high incidences of relapse- and treatment-related toxicities. As RAS deregulation is important in the pathogenesis of myeloid leukemias, targeting of RAS signaling may provide a new therapeutic strategy. Several FTIs (eg BMS-214662, L-778,123, R-115777 and SCH66336) have entered phase I and phase II clinical trials in myeloid leukemias. This review discusses recent clinical results, potential combination therapies, mechanisms of resistance and the clinical challenges of toxicities associated with prenylation inhibitors.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12886235&dopt=Abstract [PubMed - in process]

Leukemia. 2003 Aug;17(8):1508-20.
Synergistic cytotoxic effects in myeloid leukemia cells upon cotreatment with farnesyltransferase and geranylgeranyl transferase-I inhibitors.

Morgan MA, Wegner J, Aydilek E, Ganser A, Reuter CW.

Department of Hematology and Oncology, Hannover Medical School, Hannover, Germany.

As deregulation of RAS signaling is important in the pathogenesis of myeloid leukemias, molecular targeting of RAS signaling may be a promising therapeutic strategy. Farnesyl transferase inhibitors (FTIs) are the most promising class of these new cancer therapeutics. Several FTIs have entered phase II clinical trials in acute myeloid leukemia (AML). Since geranylgeranylation of K-RAS and N-RAS in the presence of FTIs may represent an important mechanism of FTI resistance, 6 geranylgeranyl transferase-I inhibitors (GGTIs) were screened alone and in combination with FTI for growth inhibition of myeloid leukemia cells. Significant growth inhibition (>70%) in myeloid cell lines was observed for GGTI-286 (9/19), GGTI-298 (14/19), GGTI-2147 (16/19) and FTI L-744,832 (17/17). GGTI treatment of NB-4 cells resulted in an accumulation of cells in G(0)/G(1), whereas FTI L-744,832 primarily caused an increase in G(2)/M. FTI and GGTIs both induced apoptosis. In all cases, FTI/GGTI cotreatment led to synergistic cytotoxic effects in both myeloid cell lines (5/5) and primary AML cells (6/6). This synergy coincided with increased apoptosis. FTI/GGTI cotreatment caused an accumulation of unprocessed N-RAS and inactive N-RAS-RAF complexes. Our results suggest that alternative geranylgeranylation of N-RAS may represent an important mechanism of resistance to FTI monotherapy in myeloid leukemia cells.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12886237&dopt=Abstract [PubMed - in process]

Heredity. 2003 Aug;91(2):112-6.
Family and population effects on disease resistance in a reptile.

Uller T, Olsson M, Madsen T.

1Department of Zoology, University of Gothenburg, Medicinaregatan 18, S-405 30 Gothenburg, Sweden. tobias.ulleool.gu.se

Despite its importance in evolutionary biology, studies of the pattern of disease resistance in natural populations are rare. In this paper, we report patterns of infection of a viral eye disease in juvenile Swedish common lizards (Lacerta vivipara). Females were sampled at random from natural populations immediately prior to parturition with equal exposure of pathogens for all lizards once in captivity. No causative agents could be found that linked risk of disease to maternal/interfollicular transfer of pathogens. The results show that a major factor influencing offspring susceptibility is family identity, suggesting heritable variation in pathogen resistance. Our interpopulation comparison provides additional support for a link between genetics and disease resistance. Lizards in northern Sweden were not only more susceptible to the disease but were also more health compromised once infected, with relatively more reduced growth rate and increased mortality than lizards from the south. This scenario suggests that southern lizards have been under selection for resistance to this pathogen, whereas northern lizards have not, or at least not to the same degree. Thus, this study confirms the importance of genetic (family) effects on pathogen resistance with variation in this trait among natural populations.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12886277&dopt=Abstract [PubMed - in process]

An Sist Sanit Navar. 2000 Sep;23(3):427-31.
[Aetiology and bacterial resistance in urinary infections of outpatiens]

[Article in Spanish]

Mazon A, Gil A, Sanchez J.

Ambulatorio General Solchaga, C/ San Fermin, 29, 31004 Pamplona, Spain. amazonrfnavarra.es

BACKGROUND. Knowledge of the etiological agents of infections of the urinary tract and of the map of the antimicrobian sensitivity of each geographic zone is a practice recommended for improving the use of antibiotics and for facilitating the choice of empirical treatment. The aim of this study is to provide up-to-date information on the pathogen flora of outpatients urinary infections in our health area and their sensitivity to antimicrobians, based on the urinary cultivations carried out in the Microbiology laboratory of the Solchaga Outpatient Surgery during the last four years. MATERIAL AND METHODS. Between 1996 and 1999, we carried out 92,816 urinary cultivations of outpatients. The urine specimens were sown on plaques with chocolate agar and MacKonkey agar with calibrated loop. The antibiogram was carried out using the Kirby-Bauer method. RESULTS. The percentage of positive urinary cultivations was 17%. Gram-negative bacilli represented 88.9% of the isolations, Gram-positive cocci 11% and yeasts 0.1%. Escherichia coli was the most frequently isolated germ (71%). The sensitivity studies show that amoxycillin-clavulanic acid, first generation cephalosprins and fosfomycin maintain a sensitivity above 80%. CONCLUSIONS. Up-to-date knowledge of the most common pathogen flora and their sensitivity to antimicrobians makes it possible for a more suitable selection to be made of the antibiotic treatment when the sensitivity pattern of the responsible germ is unavailable. In the light of the results we can conclude that amoxycillin-clavulanic acid, first generation cephalosprins and fosfomycin show a good activity in vitro, and should be considered as empirical treatments for infections of the urinary tract.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12886297&dopt=Abstract [PubMed - in process]

An Sist Sanit Navar. 2000 May;23(2):265-78.
[Trastornos de la conducta alimentaria. Revision y actualizacion]

[Article in Spanish]

Aguinaga M, Fernandez L, Varo J.

Centro de Salud Mental Ermitagana, C/ Ermitagana, 20, 31008 Pamplona, Spain.

At the present time, research into Eating Disorders is being carried out in very different areas: clinical and diagnostic, epidemiological, comorbidity, aetiopathogeny, treatment and forms of care. This paper reviews this type of pathology, and aims to update the most important data in the different fields. The epidemiological studies of recent decades would indicate a considerable increase in the rates of incidence and prevalence of both Nervous Anorexia and Nervous Bulimia. On the other hand, there is increasing confirmation of an early appearance of these disorders. Similarly, the discovery of certain physiopathological appetite markers and/or regulators opens a new path for understanding this phenomenon. Research into these problems has reached a certain consensus in aspects such as: a multidimensional consideration of the ethiopathogeny, increasingly purified diagnostic criteria, care and therapeutic procedures and resources to be used in treatment.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12886312&dopt=Abstract [PubMed - in process]

Like developmental biology of any part of our body, hair growth is a complicated process. Hence the homework for modern science to yet unravel the process and mechanism to a completion. There exist a number of traditional and alternative therapeutic methods that include drugs, surgery, suppelements, and even snake oils that have been developed and used for those who lose hair. No understanding, and there is no solution. Of course, none of these approaches are perfect for all hair loss problems, especially due to the heterogeneity of the causes underlying hair losses. Most of chemical drugs and hair transplantation surgeries are accompanied by undesirable side effects.

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