The extracellular matrix of stratum corneum: role of lipids in normal and pathological function

The mammalian stratum corneum, formerly treated as a homogeneous film, is now more properly viewed as a two-compartment system. The cornified cell is protein-enriched and lipid-depleted, lying embedded in an expanded extracellular matrix of highly nonpolar lipids. Because of its strategic location between the cornified layer, this lipid matrix is responsible for many phenomena related to the permeability barrier, as well as cohesion and desquamation. Thus, manipulation of this compartment could lead to enhanced drug delivery and improved lubrication, as well.     

Decreased Cesarean Birth Rates and Improved Perinatal Outcome: A Seven-Year Study

ABSTRACT: This study examined the decrease in cesarean section rates in relation to perinatal mortality between 1987 and 1993 at the primary referral hospital in north Jordan. Most of the population is at high risk and of low socioeconomic status. The cesarean section rate decreased from 15.5 percent in 1987 to 8.7 percent in 1993, and has remained at this low rate. During the same period the perinatal mortality dropped from 52 to 20.9 deaths per 1000 live births. These results do not include perinatal morbidity. The successful reduction of the cesarean section rate is attributed to active management of labor, trial of labor for women with a previous cesarean birth, and vaginal breech delivery in selected women. We conclude that the rate of cesarean delivery can be safely reduced in a developing country without adverse effects on birth outcomes.     

Proteasome inhibitor model of Parkinson's disease in mice is confounded by neurotoxicity of the ethanol vehicle.

Defects in the ubiquitin-proteasome system have been implicated in Parkinson's Disease (PD). Recently, a rat model of PD was developed using a synthetic proteasome inhibitor (PSI), (Z-lle-Glu(OtBu)-Ala-Leu-al). We attempted to transfer this model to mouse studies, where genetics can be more readily investigated due to the availability of genetically modified mice. We treated C57BL/6 (B6) mice with six intraperitoneal injections of 6 mg/kg PSI in 50 mul of 70% ethanol over a 2-week-period. We found significant decreases in nigrostriatal dopamine in PSI-treated mice compared with saline-treated mice. However, we observed similar decreases in the ethanol-treated vehicle control group. Administration of ethanol alone led to significant long-term alterations in dopamine levels. Ethanol significantly eclipses the effects of PSI in the dopamine system, and therefore is a confounding vehicle for this model.     

Surgery called tumoral reduction: myth or reality?]

The cytoreductive surgery (CS) or surgical debulking of tumors is supported by the following experimental concept: the maximal but incomplete resection of huge tumoral masses (debulking) induces the passage of remaining cancerous cells in proliferative cycle. So, these remaining cells become sensitive to chemotherapy, or eventually to radiotherapy. In this way, the CS appears to be a neoadjuvant treatment to the chemotherapy, this last treatment being the powerful therapeutic. In this study, we have studied successively: the theoretical basis of the CS, the experimental positive and negative arguments of this concept, and then the positive and negative clinical applications. At least, it seems that CS is more a myth than a reality, and that we should only keep the classical concepts of curative surgery or palliative surgery.     

Continuous-infusion cisplatin, 5-fluorouracil, and bolus methotrexate in the treatment of advanced non-small cell lung cancer.

BACKGROUND. Cisplatin and 5-fluorouracil have noted synergy in preclinical systems. The authors combined methotrexate with infusional cisplatin and 5-fluorouracil in an attempt to produce a regimen with improved activity in advanced NSCLC. METHODS. Twenty-six ambulatory patients with previously untreated non-small cell lung cancer were treated with continuous-infusion cisplatin (25 mg/m2/day for 5 days), 5-fluorouracil (800 mg/m2/day for 5 days), and intermediate-dose methotrexate (200 mg/m2 on days 15, 22), followed by leucovorin rescue (PFM regimen). RESULTS. Patients received a median of four cycles of therapy. Two patients had a complete response, and 10 had a partial response (overall response rate, 46.2% or 12 of 26). The median time to treatment failure was 22.5 weeks; the median survival was 55 weeks from the start of chemotherapy. There were no toxic deaths attributed to chemotherapy. Thrombocytopenia was the only Grade 4 toxicity (27%). Grade 1/4 and 2/4 peripheral neuropathy occurred in 17 of 26 patients (66%) and was associated with a cumulative cisplatin dose of more than 300 mg/m2. CONCLUSIONS. PFM (using continuous-infusion cisplatin) produced a high response rate but resulted in an high incidence of low-grade peripheral neuropathy.