The effect of "Zusanli" (ST. 36) acupuncture on the bio-availability of sodium pertechnetate in Wistar rats

The effect of acupuncture stimulation at Zusanli point (ST.36) on the bioavailability of radio-pharmaceutical 99mTc-sodium pertechnetate (Na99mTcO4) in Wistar rats was investigated. Ten healthy rats were allocated into two groups of five. Group 1 (n=5) was treated by acupuncture by inserting stainless steel needles bilaterally at ST.36; Group 2 was the untreated control. Ocular plexus administration of 0.3ml of Na99mTcO4 (3.7MBq) was carried out 10 minutes after every needle insertion. The rats were killed 25 minutes later. The organs were isolated, the radioactivity determined in a well gamma counter, and the percentage of injected radio-pharmaceutical dose per gram of tissue (%ID/g) was assessed for each organ. The %ID/g varied significantly (p<0.05) between Group 1 and Group 2 in pancreas (0.91 +/- 0.17 vs 0.15 +/- 0.03), stomach (7.97 +/- 0.68 vs 3.51 +/- 0.22), spleen (0.97 +/- 0.11 vs 0.41 +/- 0.14), brain (0.19 +/- 0.09 vs 0.09 +/- 0.04), kidneys (0.91 +/- 0.17 vs 0.15 +/- 0.03), heart (0.81 +/- 0.17 vs 0.31 +/- 0.02) and testis (0.46 +/- 0.04 vs 0.14 +/- 0.03). These findings suggest that the effect of acupuncture at ST.36 modulated organs and tissues responses in rats. Using Chinese theories of Zang-Fu and Five Phases, we suggest that the relationship between acupoints and organs may be related to neuromodulation mechanisms such as somatovisceral reflex responses, which play an important role in the autonomic nervous system. These results also suggest that the effect of acupuncture on the bio-availability of radio-pharmaceuticals may help our understanding of the action of acupuncture points on various organs and tissues.     

High-throughput techniques in breast cancer: a clinical perspective

High-throughput technologies such as DNA-microarrays, RT-PCR and proteomics can improve the prognostic and predictive information acquired from classical parameters. Unlike information gathered by classical methods, high-throughput technologies can accurately inform clinicians on patient response to adjuvant therapy or those who will resist the effect of that therapy. Studies performed in breast cancer with high-throughput techniques have focused on tumour biology, prognosis, prediction of response to a few agents and, more recently, early diagnosis. However, further refinement is needed before these techniques become part of clinical routine. In the meantime, they will be used in clinical investigation, particularly in the areas of hormonal therapy and adjuvant chemotherapy, where modest improvements in the capacity of prediction can benefit many women. Close cooperation among clinicians, pathologists and basic investigators is essential to take high-throughput techniques to daily practice. New diagnostic tools will be complex but they will provide valuable patient information.     

Potential tuberculostatic agent: micelle-forming pyrazinamide prodrug

Pyrazinamide was condensed with the poly(ethylene glycol)-poly(aspartic acid) copolymer (PEG-PASP), a micelle-forming derivative was obtained that was characterized in terms of its critical micelle concentration (CMC) and micelle diameter. The CMC was found by observing the solubility of Sudan III in Poly(ethylene glycol)-poly(pyrazinamidomethyl aspartate) copolymer (PEG-PASP-PZA) solutions. The mean diameter of PEG-PASP-PZA micelles, obtained by analyzing the dynamic light-scattering data, was 78.2 nm. The PEG-PASP-PZA derivative, when assayed for anti-Mycobacterium activity, exhibited stronger activity than the simple drug.     

Embryonic even skipped-dependent muscle and heart cell fates are required for normal adult activity, heart function, and lifespan

The Drosophila pair-rule gene even skipped (eve) is required for embryonic segmentation and later in specific cell lineages in both the nervous system and the mesoderm. We previously generated eve mesoderm-specific mutants by combining an eve null mutant with a rescuing transgene that includes the entire locus, but with the mesodermal enhancer removed. This allowed us to analyze in detail the defects that result from a precisely targeted elimination of mesodermal eve expression in the context of an otherwise normal embryo. Absence of mesodermal eve causes a highly selective loss of the entire eve-expressing lineage in this germ layer, including those progeny that do not continue to express eve, suggesting that mesodermal eve precursor specification is not implemented. Despite the resulting absence of a subset of muscles and pericardial cells, mesoderm-specific eve mutants survive to fertile adulthood, providing an opportunity to examine the effects of these developmental abnormalities on adult fitness and heart function. We find that in these mutants, flying ability, myocardial performance under normal and stressed conditions, and lifespan are severely reduced. These data imply a nonautonomous role of the affected pericardial cells and body wall muscles in developing and/or maintaining cardiac performance and possibly other functions contributing to normal lifespan. Given the similarities of molecular-genetic control between Drosophila and vertebrates, these findings suggest that peri/epicardial influences may well be important for proper myocardial function.     

Stevens-Johnson syndrome/toxic epidermal necrolysis treated with intravenous immunoglobulins

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are part of the same disease spectrum, but are differentiated by the degree of skin detachment. In TEN, more than 30 % of the body's surface area is affected; thus, it is a serious process, whose frequency is estimated at 1.2-6 cases per million population/year. We describe the case of a 75-year-old male who suffered from SJS which evolved into TEN, probably because of the ingestion of ginkgo biloba extract. He was treated with intravenous immunoglobulins (Ig IV) at a dose of 0.5 g/kg/day for five consecutive days, with favorable progress and no significant side effects. It is evident that isolated cases do not justify the systematic use of this treatment, but they may help build up experience.     

Sequencing of the Chlamydophila psittaci ompA gene reveals a new genotype, E/B, and the need for a rapid discriminatory genotyping method

Twenty-one avian Chlamydophila psittaci isolates from different European countries were characterized using ompA restriction fragment length polymorphism, ompA sequencing, and major outer membrane protein serotyping. Results reveal the presence of a new genotype, E/B, in several European countries and stress the need for a discriminatory rapid genotyping method.     

Activation of p53 by MDM2 antagonists can protect proliferating cells from mitotic inhibitors

Recent studies have shown that activation of cell cycle checkpoints can protect normal proliferating cells from mitotic inhibitors by preventing their entry into mitosis. These studies have used genotoxic agents that act, at least in part, by activation of the p53 pathway. However, genotoxic drugs are known also to have p53-independent activities and could affect the sensitivity of tumor cells to antimitotic agents. Recently, we have developed the first potent and selective small-molecule inhibitors of the p53-MDM2 interaction, the nutlins, which activate the p53 pathway only in cells with wild-type but not mutant p53. Using these compounds, we show that p53 activation leads to G1 and G2 phase arrest and can protect cells from mitotic block and apoptosis caused by paclitaxel. Pretreatment of HCT116 and RKO colon cancer cells (wild-type p53) or primary human fibroblasts (1043SK) with nutlins for 24 hours followed by incubation with paclitaxel for additional 48 hours did not increase significantly their mitotic index and protected the cells from the cytotoxicity of paclitaxel. Cancer cells with mutant p53 (MDA-MB-435) responded to the same treatment with mitotic arrest and massive apoptosis. These results have two major implications for cancer therapy. First, p53-activating therapies may have antagonistic effect when combined with mitotic poisons. Second, pretreatment with MDM2 antagonists before chemotherapy of tumors with mutant p53 may offer a partial protection to proliferating normal tissues.     

Tumor cell plasticity in Ewing sarcoma, an alternative circulatory system stimulated by hypoxia

A striking feature of Ewing sarcoma is the presence of blood lakes lined by tumor cells. The significance of these structures, if any, is unknown. Here, we report that the extent of blood lakes correlates with poor clinical outcomes, whereas variables of angiogenesis do not. We also show that Ewing sarcoma cells form vessel-like tubes in vitro and express genes associated with vasculogenic mimicry. In tumor models, we show that there is blood flow through the blood lakes, suggesting that these structures in Ewing sarcoma contribute to the circulation. Furthermore, we present evidence that reduced oxygen tension may be instrumental in tube formation by plastic tumor cells. The abundant presence of these vasculogenic structures, in contrast to other tumor types, makes Ewing sarcoma the ideal model system to study these phenomena. The results suggest that optimal tumor treatment may require targeting of these structures in combination with prevention of angiogenesis.     

HLA genes in Arabic-speaking Moroccans: close relatedness to Berbers and Iberians

The gene profile of Arabic-speaking Moroccans has been compared with those of other Mediterranean populations in order to provide additional information about the history of their origins. Our HLA data suggest that most Moroccans are of a Berber (Imazighen) origin and that Arabs who invaded North Africa and Spain in the 7th century A.D. did not substantially contributed to the gene pool; however, they imposed their advanced culture and their religion. Present-day Egyptians are also related to Moroccan Berbers and this supports an ancient Saharan origin for part of the present-day Mediterraneans, particularly for the Arabic-speaking ones (also Algerians) and also for the older substratum of Mediterranean people.