Use of Drug Kinetics in Dermis to Predict in VivoBlood Concentration After Topical Application

Purpose. To use the drug kinetics in dermis to predict the in vivo blood concentration after topical administration. Methods. A two-step pharmacokinetic model was established. The first step was to calculate the drug input rate or flux from the skin to the systemic circulation using the drug kinetic parameters in dermis. These parameters include (a) distance over which the drug concentration declines by 50%, (b) drug concentration at the epidermal-dermal junction, and (c) minimal plateauing drug concentration in the muscle layer. These parameters were experimentally determined from the drug concentration-tissue depth profiles in the dermis, after the application of a topical dose of ddI (200 mg/kg) to rats. The second step was to use the drug input rate together with the systemic disposition pharmacokinetics of ddI in rats to predict the plasma concentration-time profiles. The model-predicted plasma concentration-time profiles were compared with the observed profiles, to determine the validity of the proposed pharmacokinetic model. Results. The observed steady state concentration (C_ss) in individual animals (n = 6) deviated from the predicted values by 3 to 55% with 3 of 6 rats showing a <15% deviation. The mean observed C_ss of all animals deviated from the mean predicted values by less than 15%. Conclusions. The close agreement between the observed and the model-predicted drug concentrations indicates that the systemic drug input can be calculated from the drug kinetics in the dermis.     

Potentiation of stimulus-induced phosphoinositide breakdown by calmodulin antagonists in C6 glioma cells

To investigate the role of calmodulin (CaM)-dependent pathways in agonist-induced phosphoinositide (PI) turnover, the influence of several CaM antagonists on PI-phospholipase C (PLC) activation in intact and permeabilized C₆ glioma cells was examined. The extent of PI turnover was assessed by measuring the accumulation of inositol phosphates (IPs) in the presence of LiCl in C₆ glioma cells prelabelled with myo-[³H]inositol. Trifluoperazine, N-(6-aminohexyl)-5-chloro-l-naphthalenesulphonamide (W7), fendiline and calmidazolium themselves had no effect on basal IP formation, but concentration-dependently (1–30 M) potentiated ATP-, NaF- and A23187-stimulated IP formation. The maximal response to ATP (I mM) was increased by up to 50%, while the concentration for half-maximal effect (EC₅₀, 60 M) as unaffected by trifluoperazine. In digitonin-permeabilized C₆ glioma cells, the concentration-dependent increase of PI-PLC activation elicited by free Ca²⁺ was potentiated by the GTP analogue, guanosine 5-[-thio]triphosphate (GTPS), with an EC₅₀ of 6 M. Trifluoperazine (1–30 M) enhanced the Ca²⁺-stimulated IP formation concentration dependently and this potentiation was counteracted by the addition of CaM. In the combined presence of each CaM antagonist studied and GTPS, an additive increase in IP formation was observed. The results indicate that CaM antagonists enhance stimulus-induced IP formation in C₆ glioma cells primarily by increasing the Ca²⁺-dependent activation of PI-PLC.     

Interleukin-1Β, interleukin-6, and growth hormone levels in human follicular fluid

Purpose To investigate possible relationships of interleukin-1 (IL-1, interleukin-6 (IL-6), and growth hormone (GH) with biochemical variables in human follicular fluid (FF) and selected in vitro fertilization (IVF) parameters.Methods A total of 67 FF samples (n=67 patients undergoing oocyte retrieval for IVF) was evaluated. IL-1, IL-6, GH, hLH, FSH, PRL, hCG, testosterone, total protein, fibrinogen, sialic acid, ₁-antitrypsin, plasminogen levels, and spectrophotometric absorbance at 458 nm were analyzed for selected FF. IL-6 and GH levels of serum and FF samples were also compared (n=23).Results Immunoreactive levels of IL-1, IL-6, and GH were detected in all FF samples. A positive correlation existed for IL-6 (r=0.5069, P=0.0161 when serum-to-FF levels were compared (concentration ratio, 11.857). Smaller-volume follicles (<4 ml) were associated with high IL-1 levels (P=0.0229, and an additional tendency of IL-1 to decrease with increasing embryo cleavage and scoring was observed. With the exception of a weak positive correlation between follicular IL-1 and testosterone levels (r=0.3128, P=0.025, no other relationship with biochemical variables or IVF parameters (etiology, e.g., endometriosis) could be implicated.Conclusions Substantially higher IL-6 levels occurred in FF compared to serum, thus supporting intrafollicular production. Interleukin- 1,IL-6, and GH levels in FF are, however, unsuitable markers for in vitro fertilization outcome.     

上海市静安区(部分)儿童血铅水平状况调查

目的了解本地区儿童血铅水平现状。方法于１９９７年８月对静安区４３７例１４个月～５岁８个月的儿童进行血铅水平测定,并对每个入选儿童进行问卷调查,问卷涉及有关儿童个人情况及家庭、社会、环境等问题。结果４３７名儿童血铅水平从１５μｇ／Ｌ至６９７μｇ／Ｌ,血铅水平均数为９７．０４μｇ／Ｌ,其中血铅水平≥１００μｇ／Ｌ有１６７例,占３８．２％。本区儿童血铅水平低于工业区,高于远郊乡村,差异有显著性意义,小儿每日在马路上的时间长短为诸多影响因素中突出并存在显著性差异的因素。结论静安区虽为非工业区,但目前情况不容乐观,环境中的铅污染问题相当严重。对儿童和家长进行健康教育,规范家长和儿童的行为,是最有效、最廉价的降低儿童铅中毒患病率的方法。     

Prospective feasibility study of a mindfulness-based program for breast cancer patients in the southeastern US

BackgroundMindfulness interventions can improve psychological distress and quality of life (QoL) in cancer survivors. Few mindfulness programs for cancer recovery exist in Southeastern U.S. The primary objective of this study was to assess the feasibility of a modified mindfulness-based stress reduction (MBSR) program for breast cancer patients in Birmingham, Alabama. The secondary objective was to explore potential program effects on mindfulness skills and QoL.MethodsThis study was a prospective, quasi-experimental feasibility study conducted over 10 months at a university hospital. Feasibility was achieved if 80% of eligible patients screened enrolled in the study and 70% of enrolled patients attended all 8 program sessions. Effectiveness was estimated by changes in mindfulness and QoL indicators measured with validated scales administered at 3 time points and assessed with a non-parametric Friedman test. Sessions included meditation, yoga, and an attention practice called body scan. There were 3 groups of 2–5 patients.ResultsThe sample totaled 12 patients. Forty-four percent (12/27) of eligible patients enrolled in the study, and two out of 12 enrolled patients completed 8 program sessions, resulting in 16.7% (2/12) retention. However, more than half (66.7%) of participants completed at least 7 sessions. Between baseline and 8-week follow-up, patients demonstrated statistically significant improvements in distress, general wellbeing, and fatigue-related QoL.ConclusionsFeasibility objectives were not achieved. However, a majority of participants (66.7%) completed 7 of 8 program sessions. Program effects were promising for distress, fatigue, and wellbeing. Results warrant further research on MBSR-like programs for breast cancer patients in Alabama.     

Feasibility,acceptability and effects of dance therapy in stroke patients: A systematic review

IntroductionStroke is the leading cause of non-traumatic disability in adults, with balance and gait disturbances representing the main limitations of body functions. Dance therapy (DT) has shown positive effects in older adults and in patients with neurological pathologies. This systematic review aims to examine the feasibility, acceptability and effects of DT in stroke rehabilitation, specifically on functional gains of gait and balance.MethodsA systematic search was carried out for articles published in the MEDLINE, PEDro, Web of Science, Scopus and CINHAL in February 2021 and updated in April 2021. Results: Eight studies were included (2 clinical cases, 5 case series and 1 randomized controlled trial), 7 of them in patients with chronic stroke and only 1 in subacute stroke phase. The most widely used dance modality was tango and ballet, with sessions ranging from 30 to 110 min. DT seems to show positive effects on post-stroke body functions and activities such as gait and balance. Reported dropout rates are inconsistent, no adverse effects were reported, and participant satisfaction was high.ConclusionGiven the heterogeneity and uneven quality of the included studies, strong conclusions cannot be put forward on the effectiveness of DT in post-stroke body function and activities. Nevertheless, DT seems to be safe and acceptable therapy for patients, and no adverse effects have been reported. More studies with a high level of evidence and feasibility are needed to determine the patient profile, the characteristics of the intervention, the participation rate and the role of the rehabilitation professional most likely to generate optimal benefit.     

Pediatric intestinal transplantation

Advancements in donor management, organ preservation and operative techniques, as well as immunosuppressive therapies, have provided children with intestinal failure and its complications a chance not only for enteral autonomy but also long-term survival through intestinal transplantation (ITx). First described in the 1960’s, experience has grown in managing these complex patients both pre- and post-transplant. The goals of this review are to provide a brief history of intestinal transplantation and intestinal rehabilitation in pediatric patients, followed by focused discussions of the indications for ITx, induction and maintenance immunosuppression therapies, common post-operative complications, and outcomes/quality of life post-transplant.     

Paediatric intestinal transplantation: where are we now?

Intestinal transplantation (ITx) is the only curative treatment option for children with irreversible intestinal failure (IF) and complications of parenteral nutrition (PN). ITx is an immunologically difficult transplant due to the immune load of the donor gut; therefore, main causes of death and graft loss are immunological complications like sepsis or acute and chronic rejection. This article aims to help paediatricians in training understand when children should be referred for ITx, the different types of ITx, the complications these children might present with, and to learn about the journey a candidate for ITx must take with the support of the IF and ITx multidisciplinary teams (MDT).     

Infective endocarditis in paediatrics

Infective endocarditis is a result of infection of the endocardium, particularly of the heart valves (native or prosthetic valves). The most common causative organisms in the paediatric population are: Streptococci, Staphylococci and Enterococci. The classical signs of infective endocarditis like Roth spots, Janeway lesions, splinter haemorrhages and Osler's nodes are relatively rare in children. A high index of suspicion in a febrile child with a new murmur, detailed history, meticulous examination, repeated blood cultures, and echocardiography are essential in establishing the diagnosis. Management of infective endocarditis involves a prolonged course of antibiotics, at least for 4–6 weeks depending upon the causative organism and underlying heart condition. Complications of infective endocarditis include congestive heart failure resulting from valvular damage/regurgitation, infective emboli leading to abscesses in other organs and abnormal host immunological responses. Prophylactic antibiotics for dental and other medical procedures like genitourinary tract procedures are no longer recommended in the UK. The emphasis should be on educating children and their parents in early recognition of infective endocarditis. Children at high risk of developing endocarditis should be assessed urgently after clinical suspicion.