Israel Medical Association Journal

Background: Stem cell-based therapy is a promising approach for the treatment of neurodegenerative disease. In our laboratory, a novel protocol has been developed to induce bone marrow-derived mesenchymal stem cells into neurotrophic factor-secreting cells. These cells produce and secrete factors such as BDNF (brain-derived neurotrophic factor) and GDNF (glial-derived neurotrophic factor).

Objectives: To evaluate the migratory capacity and efficacy of NTF-SC[1] in animal models of Parkinson's disease and Huntington's disease.

Methods: MSCs[2] underwent two-phase medium-based induction. An efficacy study was conducted on the 6-hydroxydopamine-induced lesion, a rat model for Parkinson's disease. Cells were transplanted on the day of 6-OHDA[3] administration, and amphetamine-induced rotations were measured as a primary behavioral index. In a second experiment, migratory behavior was examined by transplanting cells a distance from a quinolinic acid-induced striatal lesion, a rat model for Huntington's disease. Migration, in vivo, was monitored using longitudinal magnetic resonance imaging scans followed by histology.

Results: NTF-SCs attenuated amphetamine-induced rotations by 45%. HPLC analysis demonstrated a marked decrease in dopamine depletion, post-cellular treatment. Moreover, histological assessments revealed that the engrafted cells migrated and acted to regenerate the damaged striatal dopaminergic nerve terminal network. In a preliminary work on an animal model for Huntington's disease, we demonstrated by high resolution MR images and correlating histology that induced cells migrated along the internal capsule towards the QA[4]-induced lesion.

Conclusions: The induced MSCs are a potential therapy for neurodegenerative diseases, due both to their NTF secretion and their ability to migrate towards the diseased tissue.

Stem cell research offers great hope to patients suffering from neuronal damage. Stem cell-based regenerative medicine holds huge potential to provide a true cure for patients affected by a neurodegenerative disease or who have suffered a stroke.

Progressive neurodegenerative disorders share common mechanisms of cell death, and in all likelihood multiple factors are involved in every disease. Therefore, several neuroprotective agents are being investigated with the purpose of slowing or preventing further deterioration of cell loss. These include experimental animal and clinical studies on the neuroprotective effects of caspase inhibitors, antioxitands, glutamate antagonists, anti-inflammatory agents and trophic factors in several neurodegenerative diseases. At present there is limited clinical evidence for direct neuroprotective effects against these diseases, but much effort is being invested in research on novel technologies and compounds.

Background: The degree to which serum total cholesterol predicts cariovascular disease is uncertain. While most authors have placed TC among the most powerful risk indicators of CVD, some have claimed that it predicted CVD in women only, or even not at all.

Objective: To determine the predictive value of serum total cholesterol relative to diabetes, smoking, systolic blood pressure and body mass index (kg/m2), for cardiovascular disease mortality in 3,461 occupationally active Israeli males.

Methods: A prospective follow-up was carried out for the years 1987-1998 to determine the effect of age, smoking habits, a history of diabetes, SBP, BMI and TC, at entry, on CVD mortality.

Results: There were 84 CVD deaths during a total of 37,174 person-years follow up. The hazard ratios (95% confidence intervals) for CVD mortality with respect to variables at entry were: diabetes 5.2 (2.1-13.2), age 2.2 (1.7-2.9), smoking 1.3 (1.0-1.8), SBP 1.4 (1.1-2.0), TC 1.5 (1.0-2.1) and BMI 1.2 (0.7-2.2). Among non-obese, non-diabetic, normotensive subjects the hazard ratio of TC adjusted for age and smoking was 1.16 (1.09-1.22) per 10 mg/dl. In the remaining subjects it was 1.04 (0.98-1.12) only. There was a significant interaction between TC and diabetes, hypertension or obesity (P=0.003).

Conclusions: In this population of Israeli males we found an interaction between TC and other risk indicators for CVD. Confirmation is required for the unexpected finding that the predictive value of TC for CVD mortality among non-diabetic, non-obese and normotensive subjects exceeded that among subjects with either of these risk factors.
 

Objectives: To assess the structure and the positive and negative job components of family physicians in Israel, as well as the effect of these components on their satisfaction with their work.

Methods: A questionnaire was sent to a random selection of members of the Israel Society of Family Physicians (n=225).

Results: Altogether 183 questionnaires were returned. Specialist family doctors, practice medical directors and salaried doctors were involved in more activities than non-specialist doctors, trainees and self-employed doctors. Overall satisfaction was highest for specialists and lowest for non-specialists. Work overload, insufficient resources and abundant paperwork were most frequently cited as negative work components. The opportunity to utilize medical knowledge, challenging work and work variety scored highest as positive components.

Conclusions: The more professionally active physicians were also the more satisfied. Clinical work and teaching provided the most satisfaction, while administrative work and lack of time were the main causes of dissatisfaction.

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* This article is dedicated to the memory of our dear friend, Dr. michael Herz, who contributed to the writing of it.