The binding of blood-borne estrogens in normal vegetarian and omnivorous women and the risk of breast cancer

Serial blood samples were taken at two-hour intervals over a 24-hour period from 25 premenopausal vegetarians (12 vegans and 13 ovolactovegetarians) and from 21 omnivorous controls. All members of the former group had been on a vegetarian diet for a minimum of three years. The mean proportion of estradiol unbound to blood proteins was similar in both vegetarians (1.26%) and meat eaters (1.16%). However, the amount bound to albumin was significantly raised in vegetarians (50.1% vs. 43.1%, p less than 0.009), whereas that bound to sex hormone-binding globulin (SHBG) was correspondingly lower (48.7% vs. 55.8%, p = 0.01). Mean levels of SHBG were similar in vegetarians (59.9 nmole/l) and omnivores (62.0 nmole/l), as was the total amount of free fatty acid (0.42 mmole/l for both). Within the vegetarian group, no differences were detected between vegans and ovolactovegetarians.     

A proposed autacoid mechanism controlling mastocyte behaviour

Evidence is provided here supporting the existence of a novel autacoid mechanism negatively modulating mast cell behaviour in response to noxious stimuliin vivo; hence, the denomination “autacoid local inflammation antagonism” (ALIA). In particular, as lipid amides of theN-acylethanolamine type have been reported to accumulate in tissues in degenerative inflammatory conditions, we examined whether theseN-acylated lipids could exert regulatory effects on mast cell activationin vivo. The results reported show that both long- and short-chainN-acylethanolamines, when systemically administered, are effective in reducing mast cell degranulation induced by local injection of substance P in the earpinna of developing rats. These and other data suggest that the endogenous production ofN-acylethanolamines may constitute a local autocrine/paracrine response for the negative feedback control of mast cell responses to various activating signals. Such a process may be of physio-pathological relevance in the regulation of functional neuroimmune-mast cell interactions.

     

Patients' and family members' perspectives on the benefits and working mechanisms of family nursing conversations in Dutch home healthcare

The aim of this study is to propose a model of the benefits and working mechanisms of family nursing conversations in home healthcare from the perspective of participating patients and their family members. Family nursing conversations in this study are intended to optimise family functioning, improve collaboration between family and professional caregivers and ultimately prevent or reduce overburden of family caregivers. In a qualitative grounded theory design, data were collected in 2017 using intensive interviewing with participants of family nursing conversations in home healthcare. A total of 26 participants (9 patients and 17 family members) from 11 families participated in a family nursing conversation and the study. Seven nurses who received extensive education in family nursing conversations conducted them as part of their daily practice. Interviews occurred 4–6 weeks after the family nursing conversation. The model that was constructed in close collaboration with the families consists of three parts. The first part outlines working mechanisms of the conversation itself according to participants, i.e. structured and open communication about the care situation and the presence of all of the people who are involved. The second part consists of the benefits that participants experienced during and immediately after the conversation – an increased sense of overview and improved contact among the people involved – and the related working mechanisms. The last part consists of benefits that emerged in the weeks after the conversation – reduced caregiver burden and improved quality of care – and the related working mechanisms. Insight into the benefits and working mechanisms of family nursing conversations may assist healthcare professionals in their application of the intervention and provides directions for outcomes and processes to include in future studies.     

Dual Action of NAMI-A in inhibition of solid tumor metastasis: selective targeting of metastatic cells and binding to collagen.

NAMI-A is a ruthenium complex endowed with a selective effect on lung metastases of solid metastasizing tumors. The aim of this study is to provide evidence that NAMI-A's effect is based on the selective sensitivity of the metastasis cell, as compared with other tumor cells, and to show that lungs represent a privileged site for the antimetastatic effects. The transplantation of Lewis lung carcinoma cells, harvested from the primary tumor of mice treated with 35 mg/kg/day NAMI-A for six consecutive days, a dose active on metastases, shows no change in primary tumor take and growth but a significant reduction in formation of spontaneous lung metastases. Transmission electron microscopy examination of lungs and kidney shows NAMI-A to selectively bind collagen of the lung extracellular matrix and also type IV collagen of the basement membrane of kidney glomeruli. The half lifetime of NAMI-A elimination from the lungs is longer than for liver, kidney, and primary tumor. NAMI-A bound to collagen is active on tumor cells as shown in vitro by an invasion test, using a modified Boyden chamber and Matrigel, and it inhibits the matrix metallo-proteinases MMP-2 and MMP-9 at micromolar concentrations, as shown in vitro by a zimography test. These data show NAMI-A to significantly affect tumor cells with metastatic ability. Binding to collagen allows NAMI-A to exert its selective activity on metastatic cells during dissemination and particularly in the lungs. These data also stress the wide spectrum of daily doses and treatment schedules at which NAMI-A is active against metastases.     

Association of CYP2C8, CYP3A4, CYP3A5, and ABCB1 polymorphisms with the pharmacokinetics of paclitaxel.

PURPOSE: To retrospectively evaluate the effects of six known allelic variants in the CYP2C8, CYP3A4, CYP3A5, and ABCB1 genes on the pharmacokinetics of the anticancer agent paclitaxel (Taxol). EXPERIMENTAL DESIGN: A cohort of 97 Caucasian patients with cancer (median age, 57 years) received paclitaxel as an i.v. infusion (dose range, 80-225 mg/m(2)). Genomic DNA was analyzed using PCR RFLP or using Pyrosequencing. Pharmacokinetic variables for unbound paclitaxel were estimated using nonlinear mixed effect modeling. The effects of genotypes on typical value of clearance were evaluated with the likelihood ratio test within NONMEM. In addition, relations between genotype and individual pharmacokinetic variable estimates were evaluated with one-way ANOVA. RESULTS: The allele frequencies for the CYP2C8*2, CYP2C8*3, CYP2C8*4, CYP3A4*3, CYP3A5*3C, and ABCB1 3435C>T variants were 0.7%, 9.2%, 2.1%, 0.5%, 93.2%, and 47.1%, respectively, and all were in Hardy-Weinberg equilibrium. The population typical value of clearance of unbound paclitaxel was 301 L/h (individual clearance range, 83.7-1055 L/h). The CYP2C8 or CYP3A4/5 genotypes were not statistically significantly associated with unbound clearance of paclitaxel. Likewise, no statistically significant association was observed between the ABCB1 3435C>T variant and any of the studied pharmacokinetic variables. CONCLUSIONS: This study indicates that the presently evaluated variant alleles in the CYP2C8, CYP3A4, CYP3A5, and ABCB1 genes do not explain the substantial interindividual variability in paclitaxel pharmacokinetics.     

Addressing Challenges to Providing Peer-Based Recovery Support

As more systems of care deploy peer-based recovery support (P-BRS) programs, challenges to the effective use of P-BRS have emerged. These include external challenges, embedded in the organization and culture of traditionally organized services, and individual challenges, associated with the nonprofessional status of individual peer support staff members. The Living Centers, recovery resource centers providing P-BRS, have developed methods for addressing these challenges. These include organizing the P-BRS as stand-alone programs, having peer support staff and clients organize the P-BRS, emphasizing organizational values and culture as the basis for staff training, and implementing measures designed to encourage accountability among peer support staff. In the future, research into the types of barriers to P-BRS that may exist in traditionally organized behavioral health services and the types and content of training that contribute to the provision of P-BRS will facilitate the use of these services.     

Efficacy and safety of pegylated liposomal doxorubicin in primary cutaneous B‐cell lymphomas and comparison with the commonly used therapies

Objectives: The therapy of advanced, relapsed or refractory primary cutaneous lymphomas is often unsatisfactory. Recent data indicate a favourable pharmacokynetic, pharmacodynamic and toxicity profile of pegylated liposomal doxorubicin (Peg‐Doxo) in primary cutaneous T‐cell lymphomas, while in primary cutaneous B‐cell lymphomas (PCBCLs), the drug efficacy has never been assessed so far. Methods: We performed a prospective phase II pilot clinical trial of Peg‐Doxo monotherapy (20 mg/m²) in PCBCLs. One patient had a marginal zone B‐cell lymphoma and four were affected by diffuse large B‐cell lymphoma‐leg type, all with widespread nodular lesions. Results: All the patients achieved a complete response (CR = 100%) in a short period of time (median 3 months), even when pretreated with radio‐chemotherapy. Two experienced a relapse. At follow‐up, one patient died for progressive disease; four are in CR after 5, 52, 63 and 69 months. As concerning the toxicity profile, the treatment was well‐tolerated, no one decreased or delayed the dose. The haematological toxicity was mild with only one case of grade III neutropenia; a patient showed a grade I neurotoxicity. Dermatological toxicity, in particular the palmar–plantar erythrodysesthesia, did not occurred, probably because of both the low dosages of Peg‐Doxo monotherapy and the oral prophylaxis with pyridoxine. Conclusions: In spite of the small number of patients, it emerges that monochemotherapy with Peg‐Doxo has a significantly high clinical activity and a good safety profile in PCBCLs, even in aggressive forms, compared with other therapeutic regimens, which are completely reviewed. It suggests the need of further investigations in this field.     

Confocal Laser Scanning Microscopy of Liesegang Rings in Odontogenic Cysts: Analysis of Three-Dimensional Image Reconstruction

Liesegang rings are concentric noncellular lamellar structures, occasionally found in inflammatory tissues. They have been confused with various parasites, algas, calcification, and psammoma bodies. The authors examined Liesegang rings from oral inflammatory cysts by both optical and confocal laser scanning microscopy, and perfomed a three-dimensional reconstruction. These investigations indicate that Liesegang rings are composed of multiple birefringent concentric rings, resulting from a progressive deposition of organic substances, with an unclear pathogenesis.