Evaluation of the Isoconversional Approach to Estimating the Hoffman‐Lauritzen Parameters from the Overall Rates of Non‐Isothermal Crystallization of Polymers

Summary: The isoconversional approach proposed by Vyazovkin for evaluating the Hoffman‐Lauritzen parameters from overall rates of non‐isothermal crystallization was critically applied to two new and fast crystallizing polymers, poly(propylene terephthalate) and poly(butylene naphthalate), which are used for the production of fibers. Non‐isothermal crystallization data were corrected for the effect of the thermal lag and the effective activation energy as a function of temperature was calculated using the method of Friedman. The estimated Hoffman‐Lauritzen parameters, U* and K_g, were consistent with corresponding values from isothermal crystallization experiments obtained either from DSC measurements or using polarized optical microscopy (POM). It was found that the proposed method could simulate the experimental data very well, and the temperature interval under consideration did not allow the detection of any critical breakpoints denoting regime transitions.

Dependence of the effective activation energy on average temperature for PPT.     

Targeting vascular risk in patients with metabolic syndrome but without diabetes

There are no prospective data on the effect of a multitargeted treatment approach on cardiovascular disease (CVD) risk reduction in nondiabetic patients with metabolic syndrome (MetS). Furthermore, the optimal hypolipidemic drug treatment in these patients remains controversial. In this prospective, randomized, open-label, intention-to-treat, and parallel study, 300 nondiabetic patients with MetS, free of CVD at baseline, were studied for a period of 12 months. Age- and sex-matched subjects without MetS (n = 100) acted as controls. All patients received lifestyle advice and a stepwise-implemented drug treatment of hypertension, impaired fasting glucose, and obesity. For hypolipidemic treatment, the patients were randomly allocated to 3 treatment groups: atorvastatin (n = 100, 20 mg/d), micronized fenofibrate (n = 100, 200 mg/d), and both drugs (n = 100). Clinical and laboratory parameters, including the lipid profile and C-reactive protein (CRP), were assessed at the baseline and at the end of the study. The primary end point was the proportion of patients not having MetS or its component features at the end of the 12-month treatment period. The secondary end points were the difference in 10-year CVD risk (Prospective Cardiovascular Munster risk calculator) and the degree of CRP reduction. By the end of the study, 76% of the patients no longer had MetS, and 46% had only one diagnostic MetS factor. The estimated 10-year (Prospective Cardiovascular Munster) risk of all patients with MetS at baseline was 14.6%. This was reduced in the atorvastatin group to 6.4%, in the fenofibrate group to 9.2%, and in the combination group to 5.5% (P < .0001 for all vs baseline). The 10-year risks of the atorvastatin and combination groups were not different from that of the control group (5.0%). C-reactive protein was significantly reduced in all treatment groups, with the atorvastatin and combination groups having the greatest reduction (65% and 68%, respectively, P < .01 vs the fenofibrate group, 44%). Lipid values were significantly improved in all 3 treatment groups, with those on the combined treatment attaining lipid targets to a greater extent than those in the other 2 groups. A target-driven and intensified intervention aimed at multiple risk factors in nondiabetic patients with MetS substantially offsets its component factors and significantly reduces the estimated CVD risk. The atorvastatin-fenofibrate combination had the most beneficial effect on all lipid parameters and significantly improved their CVD risk status. Atorvastatin and combination treatment were more effective than fenofibrate alone in reducing CRP levels.     

Laparoscopic restaging of early stage invasive adnexal tumors: a 10-year experience

Surgical staging of apparent early stage adnexal carcinoma provides indispensable information. A significant number of patients are referred to tertiary centers with inadequate staging information. We report on our experience with late results of laparoscopic restaging procedure in uncompletely managed early adnexal carcinomas. MATERIALS AND METHODS: From 1991 to 2001, 53 laparoscopic restaging operations were performed: 42 patients were restaged early after initial surgery for an ovarian carcinoma (OC) in 35 of them, and for fallopian tube carcinomas (FTCs) in 7 others. Eleven patients were assessed as a second-look procedure, after six courses of platinum-based chemotherapy indicated for a high-risk tumor. The procedure systematically followed the guidelines of laparotomy. RESULTS: All except one (adhesions) procedures were successfully completed. Operative room time averaged 238 min and hospital stay 3.1 days. Only one major complication required laparotomy (1.8%). In the primary restaging group, eight patients were upstaged (19%) and were given chemotherapy. After a 54-month median follow-up, 3 out of the 34 remaining patients diagnosed as stage IA grades 1-2 (6.4%) recurred and died. In the group of 11 second-look operations, 4 were found positive after chemotherapy. One of the positive patient recurred and died. CONCLUSIONS: Laparoscopy seems to be an acceptable technical option to perform restaging of apparently early adnexal carcinomas. It spares the patients the discomfort of repeat laparotomy. Long-term outcome results suggest that laparoscopic staging, provided it meets the standards, accurately detects the patients who need chemotherapy and safely select the patients who can be proposed surgery only.     

Role of tumor necrosis factor-related apoptosis-inducing ligand in interferon-induced apoptosis in human bladder cancer cells

Immunomodulators such as Bacillus Calmette-Guerin and interferon are clinically active in transitional cell carcinoma of the bladder, but their mechanisms of action remain unclear. Here we investigated the effects of IFNalpha on tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) expression and apoptosis in a panel of 20 human bladder cancer cell lines. Six (30%) displayed significant DNA fragmentation in response to increasing concentrations of IFNalpha (10-100,000 units/mL). In these lines IFNalpha induced early activation of caspase-8, and DNA fragmentation was blocked by a caspase-8-selective inhibitor (IETDfmk), consistent with the involvement of death receptor(s) in cell death. IFNalpha stimulated marked increases in TRAIL mRNA and protein in the majority of IFN-sensitive and IFN-resistant cell lines. A blocking anti-TRAIL antibody significantly inhibited IFN-induced DNA fragmentation in four of six IFN-sensitive cell lines, confirming that TRAIL played a direct role in cell death. Bortezomib (PS-341, Velcade), a potent TRAIL-sensitizing agent, increased sensitivity to IFNalpha in two of the IFN-resistant cell lines that produced large amounts of TRAIL in response to IFN treatment. Our data show that IFN-induced apoptosis in bladder cancer cells frequently involves autocrine TRAIL production. Combination therapy strategies aimed at overcoming TRAIL resistance may be very effective in restoring IFN sensitivity in a subset of human bladder tumors.     

Long-term abstinence syndrome in heroin addicts: indices of P300 alterations associated with a short memory task

Attentional deficits have been implicated in the pathophysiology of opioid addicts. The P300 component of event-related potentials (ERPs) is considered as a manifestation of attentional operations. The authors' goal was the comparison of P300 elicited during a short memory test between subjects with prolonged heroin abstinence and current heroin users as well as healthy controls. The P300 component was evaluated during the anticipatory period of a short memory task in 20 patients characterized by a past history of opioid dependence (6 months abstinence), in 18 current heroin users and in 20 healthy comparison subjects, matched for age, sex and educational level. Abstinent heroin addicts exhibited significant reduction of P300 amplitude at central frontal region, relative to the other two groups. The findings are discussed in connection to the aim of identifying psychophysiological indices, addressing issues in opioid use disorders, and suggest that knowledge about cognitive operations, such as those reflected by P300 component, could provide further insight into psychophysiological mechanisms underlying the long-term abstinence state of heroin addicts.     

Preparation and release studies of alkannin-containing microcapsules

Microcapsules containing the pharmaceutical substance alkannin were prepared by the solvent evaporation method to enhance alkannin stability (reduce photo-oxidation, polymerization), to decrease its hydrophobicity and to control its release rate. The effect of various parameters, such as the type of polymeric matrix, the type of surfactant used for microcapsules preparation and the addition of Pistacia lentiscus resin in the core, on the characteristics of the produced microcapsules and the release rate of alkannin were investigated experimentally. Among the polymers tested for matrix, ethylcellulose of viscosity 46cp was the most successful, while ethylcellulose 10cp gave microcapsules with good morphological characteristics but high release rate. Beeswax resulted in flocculation and P. lentiscus resin with or without colophony as the matrix resulted in compact particles with no pores and much slower release, but did not allow alkannin to release easily from the matrix. Sodium dodecyl sulfate resulted in microcapsules with desirable morphological and physicochemical characteristics, while acacia and tragacanth gums were not indicated as surfactants in alkannin microencapsulation since they gave a high release rate and a great extent of particle size, respectively. The incorporation of Pistacia lentiscus resin in the capsule core increased loading and microencapsulation efficiency. Ethylcellulose of 46cp viscosity with sodium dodecyl sulfate as surfactant had the best characteristics studied for alkannin microencapsulation. Finally, the dissolution rate of alkannin from microcapsules was studied in a simulated intestinal and gastric environment and an external environment. Alkannin-containing microcapsules with improved properties can be used internally and externally as a new drug-delivery system.     

The allylic 7-ketone at the steroidal skeleton is crucial for the antileukemic potency of chlorambucil's active metabolite steroidal esters

We have investigated the role of the allylic 7-ketone in oxidized Delta5-steroids on antileukemic activity. We synthesized and studied a series of oxidized and non-oxidized steroidal esters of p-N,N-bis(2-chloroethyl)aminophenylacetic acid (PHE), chlorambucil's active metabolite. In a comparative study of these 7-keto derivatives, on a molecular basis, regarding their ability to induce sister chromatid exchanges (SCEs) and to inhibit cell proliferation in normal human lymphocytes in vitro, the results with these 7-keto derivatives, on a molecular basis, correlated well with their antileukemic potency against leukemia P388- and L1210-bearing mice, which proved to be significantly increased compared to that of the non-oxidized derivatives. Our results indicate that the role of the steroidal skeleton it is not only for the transportation of the alkylating agent into the cell, but also contributes directly to the mechanism of antileukemic action, by an as-yet unknown way. The main conclusion from this study is that the existence of the allylic 7-keto group in the skeleton of the Delta5-steroidal esters impressively enhances their antileukemic activity, while the toxicity remains at clinically acceptable levels, suggesting that this structural modification should be further investigated.     

Endometrial cancer: what's new?

OBJECTIVES: New and much debated data of the endometrial cancer concerning the preoperative assessment of myometrial invasion, the surgical staging, and the adjuvant treatment. PATIENTS AND METHODS: Medline (1998-2002): searching for "endometrial carcinoma". RESULTS: The pap smears are useful when it is difficult to have a transvaginal ultrasonography or an MRI. We can perform the pap smears and the endometrial biopsy in the clinic. If a patient has pap smears with malignant cells or elevated preoperative CA 125, it probably is a cancer with poor prognostic factors. Surgical staging with abdominal and node evaluation is necessary. The MRI seems to be the best preoperative imaging because we have information about adnexal and abdominal metastases, pelvic or aortic nodes and the invasion of the myometrium. So it gives us information on the surgical route, and provides indication for a lymphadenectomy. The surgical staging is a part of the treatment of the endometrial cancer: an exploration of the peritoneal cavity, a pelvic lymphadenectomy, a para-aortic lymphadenectomy if the pelvic nodes are positive or if there are factors of bad prognosis (deep stage IC, grade 3, adnexal or abdominal involvement, serous carcinoma of the endometrium). It can be performed if technical conditions are correct. The adjuvant teletherapy in the documented stage IpN0 (surgical staging with pelvic lymphadenectomy) does not seem to be necessary. But we can perform an adjuvant brachytherapy (high-dose rate if it is possible) in patients with a high local recurrence (stage IC, stage I with grade 3, stage IB grade 2). CONCLUSION: The preoperative MRI is useful choosing the surgical approach, and the depth of the myometrial invasion, which can be an indication for a pelvic lymphadenectomy. The surgical staging must be a part of the treatment of the endometrial cancer. So the adjuvant teletherapy in patients with stage IpN0 documented should not be used.