Drug development from natural products: Exploiting synergistic effects.

Drug development in phytomedicine has been focused in the past on the discovery and analysis of new structures from natural products. The search aimed at the determination of the single “active principle” in plants, based on the assumption that a plant has one or a few ingredients which determine its therapeutic effects. But traditional systems of medicines like Ayurveda, traditional Chinese medicine or the European phytotherapy generally assume that a synergy of all ingredients of the plants will bring about the maximum of therapeutic efficacy. This approach has for long been impossible to investigate since adequate methods to standardize complex plant mixtures as well as to rationalize complex mode of actions were lacking. The introduction of high throughput technologies provides the opportunity to determine profiles of plants and to systematically explore the mode of action of combinatory drug regimes. The present review highlights the concept of synergy and gives examples of synergistic effects of plant constituents. It elaborates on how the high throughput technologies can be used in drug development from natural products with the aim of creating evidence-based plant medications in prevention and treatment of different diseases in the form of new single treatments or new combinatory drug regimes while exploiting synergy-effects.

Reducción anatómica percutánea en luxofractura de Lisfranc de baja energía / Percutaneous anatomical reduction in low energy Lysfranc fracture

Report the quality of reduction and results of percultaneously operated Lisfranc fracture patients: Methods: We retrospectively evaluated 10 patients with low energy Lisfranc fractures operated between July 2007 and March 2009. There were 6 men and 4 women with an average age of 32,3 years and an average follow up 11,6 months. We evaluated reduction quality in digital x rays, functional results and subjective satisfaction. Results: Quality of reduction was anatomic in 100 percent of cases. Time to return to work was at an average of 7,2 weeks, sports 7,6 weeks, daily life activities at 7,2 weeks. Overall subjective satisfaction was 100 percent. No patient reported persistent edema or pain. 5 patients had mild pain after strenuous physical activities. Conclusion: In these selected low energy Lisfranc fracture patients the result after a reproducible technique are excellent with minimal persistent symptoms. We strongly believe that adequate reduction can be obtained through a percutaneous approach in almost every Lisfranc fracture case.

Objetivo: Mostrar la calidad de la reducción y resultados funcionales a corto y mediano plazo de pacientes operados de luxofractura de Lisfranc vía percutánea. Métodos: Estudio retrospectivo de una serie consecutiva de 10 pacientes operados de luxofractura de Lisfranc vía percutánea entre Julio de 2007 y Marzo de 2009. Seis hombres y 4 mujeres, promedio de edad de 32,3 años. El tiempo de seguimiento promedio fue de 11,6 meses. Se revisaron protocolos quirúrgicos, fichas clínicas y se contactaron vía telefónica. Se evalúo los resultados funcionales, grado de satisfacción con la cirugía y calidad de la reducción mediante radiografías digitales. Resultados: La reducción fue anatómica en los 10 pacientes. El tiempo promedio de retorno laboral fue de 7,2 semanas. Ningún paciente refirió edema o dolor con las actividades de la vida diaria y 5 pacientes dolor leve tras realizar actividad física. Ningún paciente refirió uso actual de ortesis. El grado de satisfacción con la cirugía fue favorable en los 10 pacientes. Conclusión: En este grupo seleccionado de pacientes, con el diagnostico de luxofractura de Lisfranc tras un tratamiento de baja energía, es factible de una reducción anatómica mediante técnica percutánea. Creemos que la técnica percutánea no sacrifica la calidad de la reducción.

Anastomosis ileorrectal en el tratamiento quirúrgico de la colitis ulcerosa: resultados a largo plazo / Ileorectal anastomosis in the surgical treatment of ulcerative colitis: long-term results

Background: Total colectomy with ileorectal anastomosis (IRA) is an alternative to the ileoanal pouch for the surgical treatment of ulcerative colitis in a selected group of patients. This technique leaves rectal mucosa Hable to develop persistent proctitis, dysplasia and cancer Aim: To describe short and long-term results of IRA and to assess the presence of dysplasia. Material and methods: Descriptive study of patients treated with IRA. The data were obtained from the clinical records, and the present status was evaluated with an interview. A proctoscopy and biopsy was offered free of cost to the contacted patients. Results: Between 1978 and 2005, 26 patients were operated. One patient presented an anastomotic leakage that was treated with a loop ileostomy There was no operative mortality. Twenty-three patients were followed for a períod of 1 to 23 years. Three patients evolved as Crohn 's disease and two of them needed a proctectomy. Three patients died of non-related diseases. In the remaining 17, the average evacuation rate was 3.7/24 h and all were continent. None developed a rectal cancer Only two patients had their planned annual endoscopic surveillance. In 2 of the 11 patients who accepted endoscopy and biopsy, a low-grade dysplasia was found. Conclusions: IRA has low morbidity and acceptable functional results in this selected group of patients. No patient present high-grade dysplasia or cancer; however, the adherence to the endoscopic follow-up ispoor.

Biological activity of the aqueous extract of Lychnophora pinaster Mart.

Lyophilized aqueous extract (LAE) from Lychnophora pinaster Mart (Asteraceae) aerial parts was evaluated in the search of possible biological activities. LAE exhibited trypanocidal activity (113.62 mg/mL), but could not inhibit 5-lipoxygenase in vitro (17 percent of inhibition). LAE chemical characterization by HPLC with UV-Diode Array Detector showed the presence of caffeic acid, isochlorogenic acid, vitexin, isovitexin and quercetin, in comparison with authentic samples.

Estudo quimico de Zeyheria montana M. (bolsa de pastor)

Do extrato hexânico das raízes de Zeyheria montana M., uma Bignoniácea conhecida como bolsa‑de‑pastor, empregada popularmente contra doenças de pele, foram isolados os seguintes compostos: lapachol, α‑lapachona, desidro‑α‑lapachona, 4‑hidróxi­-α‑lapachona, β‑sitosterol, ácido esteárico e uma mistura de ácidos graxos. Estas substancias foram identificadas por métodos espectrométricos usuais e/ou comparação com amostras autênticas. No cromatograma do extrato etanólico, obtido por CLAE, foram identificados os picos correspondentes às naftoquinonas isoladas e ao ácido esteárico. A ocorrência de naftoquinonas nas raizes de Z. montana e a atividade antimicrobiana comprovada para o lapachol e a α‑lapachona justificam o uso popular desta espécie.

Zeyheria montana M. (Bignoniaceae) is a widespread species in the Cerrado area of Minas Gerais, Brazil, and is popularly known as bolsa‑de‑pastor. In the Brazilian tradicional medicine its roots are used for the treatment of skin diseases. Several species of Bignoniaceae contain naphthoquinones, and lapachol was previously reported in the stem wood of Z. digitalis. This paper describes the isolation of three naphtoquinones from Z. montana stem barks, namely α‑lapachone, dehydro‑α‑lapachone and 4‑hydroxy‑α‑lapachone, besides lapachol, stearic acid and β‑sitosterol. Furthermore, we report the HPLC fingerprint for the species, which allowed the identification of the isolated compounds, except β‑sitosterol. Since the in vitro antimicrobial activity of lapachol and α‑lapachone has been previously described, the presence of these naphthoquinones in the roots of Z. montana corroborates its popular use for the treatment of skin diseases.

Artroplastía total de rodilla con prótesis de estabilización posterior: 10 años de experiencia / Total knee arthroplasty with posterior stabilized prosthesis: 10 years experience

Se presenta una serie de 66 pacientes operados en el Hospital Clínico de la Univerdidad Católica de Chile entre 1989 y 1999, con un total de 71 rodillas sometidas a artroplastía. El grupo estudiado consistió en 49 mujeres (edad promedio 67,4 años, rango 36-83) y 17 hombres (edad promedio 66.8 años, rango 21-82). Los diagnósticos fueron artrosis primaria (72 por ciento), artritis reumatoide (25 por ciento) y otros (3 por ciento). El puntaje promedio preoperatorio según el score del H.S.S.N.Y. fue 51 puntos (rango 27-66). En todos los pacientes se realizó una misma técnica quirúrgica y un programa postoperatorio uniforme. Los modelos protésicos utilizados fueron Insall Burstein (68 por ciento), Nex Gen (25 por ciento) y Osteonics (7 por ciento). El tiempo promedio de evolución postoperatoria es de 44 meses (rango 6-108). Se lograron resultados buenos a excelentes (85 a 100 puntos) en un 93 por ciento de las rodillas. Se presentan los resultados de la evaluación funcional y radiológica, así como las complicaciones. Se presentaron 2 infecciones precoces y dos tardías

Cell cycle control and cancer.

This review consists of two parts. In the first part normal mechanisms regulating the progression of cells through the cell cycle are briefly reviewed. Besides mitogenic stimulation, cyclin kinase inhibition, the G1 restriction point and the prb pathway, accuracy of DNA replication and DNA repair, the G2 to M transition, apoptosis and the p 53 pathway, proteolytic, in particular ubiquitin-dependent mechanisms involved in the initiation of DNA synthesis in the separation of sister chromatids and in the telophase to GO/G1 transition, are discussed. In the second part oncogene and tumor suppressor gene products are briefly characterized. Aberrations of cell cycle control mechanisms associated with cancer are grouped as follows: deregulation of protooncogenes by translocations juxtaposing protooncogenes to immunoglobulin--or T cell receptor genes; translocations producing chimeric proteins unique to cancer cells; inversions and amplifications resulting in over expression of regulator genes; and deletions and mutations of tumor suppressor genes. It is emphasized that cancer is the result of a multistep process and that uncontrolled cell production and other alterations are, as a rule, late phenomena.