Sustainable mechanochemical synthesis of β-cyclodextrin polymers by twin screw extrusion

Cyclodextrin nanosponges (CD-NS) are cross-linked cyclodextrin polymers characterized by a nanostructured three-dimensional network. CD-NSs in the last years found many different applications in the pharmaceutical field for the controlled release of drugs and for the absorption of undesired substances from physiological media, food, and wastewater. Most of CD-NS syntheses involve the solubilization of the chosen CD in closed batch, using a suitable organic polar aprotic liquid, which may affect potential environmental or biomedical applications. Since the research is now moving towards more sustainable approaches, new and greener syntheses of CD-NS are now being developed. Here, it is reported a new eco-friendly and efficient synthesis of nanosponges through mechanochemistry. Mechanochemistry involves the application of mechanical forces to drive and control chemical reactions by transferring energy to chemical bonds. The mechanochemical approach involves the use of a twin-screw extruder (TSE) as a chemical reactor: TSE are capable of fine temperature control and, furthermore, TS Extrusion is a continuous process and not a batch process. Among the many available CD-NS syntheses, we tested our solvent-free approach on a β-CD/citric acid (CA) system. Moreover, using TSE, the same polymer was obtained in a considerably shorter time. The so obtained NSs were used for the adsorption and removal of probe molecules, in comparison with NSs prepared by cross-linking β-CD with CA in batch. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11356-021-15187-5

Intermittent Pringle Maneuver and Hepatic Function: Perioperative Monitoring by Noninvasive ICG-Clearance

BACKGROUND: Intermittent Pringle maneuver or selective portal clamping often are used to control inflow during parenchymal liver transection. This study was designed to determinate whether these maneuvers are associated with adverse hepatic function. METHODS: Resection was performed without portal clamping in 17 patients (group 1). Selective continuous portal clamping was performed in 11 patients (group 2) and the remaining 33 patients (group 3) had intermittent nonselective portal clamping (occlusion of the main portal trunk). The centers' protocol for total portal occlusion is 15-min occlusion alternated with 5-min reperfusion in patients with normal liver parenchyma or 10 min alternated with 5 min in patients with abnormal parenchyma. ICG elimination tests were conducted concurrently using a noninvasive monitor that tracks the plasma disappearance rate (PDR-ICG-%/min) and 15-min retention rate after administration (ICG-R15-%). RESULTS: There was no statistically difference between the three studied groups in terms of sequential changes of ICG-PDR (p < 0.625) or ICG-R15 (p < 0.398). CONCLUSIONS: Our study indicates that 15 min of intermittent Pringle maneuver or selective hemihepatic continuous portal clamping are safe methods of vascular control during liver resection, with no adverse effects on hepatocellular function

Hepatectomy and liver regeneration: from experimental research to clinical application

BACKGROUND: The mechanisms and kinetics of hepatic growth have continuously been investigated. This study concerns liver regeneration in animal and patients who underwent partial hepatectomy evaluated by the hepatic extraction fraction (HEF) calculated through radioisotopic methods. METHODS: Thirty normal Wistar rats were submitted to an 85% hepatectomy, and 95 patients with primary and secondary liver tumours were included. In animal study, the liver regeneration kinetics was assessed by HEF using 99mTc-mebrofenin, the ratio liver/bodyweight and by using bromodeoxyuridine deoxyribonucleic acid incorporation. In patient study, the liver regeneration was evaluated by calculation of HEF before surgery, 5 and 30 days after hepatectomy. RESULTS: In animal, we verified a positive correlation between HEF kinetics and liver/bodyweight ratio or hepatocyte proliferation evaluated by bromodeoxyuridine deoxyribonucleic acid staining after 85% hepatectomy. In the clinical arm, no statistical differences of the HEF before hepatectomy, 5 and 30 days after hepatectomy, were observed. CONCLUSIONS: Our results support the view that human liver regeneration commences early, is fast, non-anatomical and functionally complete 5 days after hepatectomy. The fast functional liver regeneration may have a high clinical impact particularly concerning the post-operative oncological therapeutic approaches.info:eu-repo/semantics/publishedVersio

Avoiding Treatment Interruptions: What Role Do Australian Community Pharmacists Play?

OBJECTIVE: To explore the reported practice of Australian community pharmacists when dealing with medication supply requests in absence of a valid prescription. METHODS: Self-administered questionnaire was posted to 1490 randomly selected community pharmacies across all Australian states and territories. This sample was estimated to be a 20% of all Australian community pharmacies. RESULTS: Three hundred eighty five pharmacists participated in the study (response rate achieved was 27.9% (there were 111 undelivered questionnaires). Respondents indicated that they were more likely to provide medications to regular customers without a valid prescription compared to non-regular customers (p&lt;0.0001). However, supply was also influenced by the type of prescription and the medication requested. In the case of type of prescription (Standard, Authority or Private) this relates to the complexity/probability of obtaining a valid prescription from the prescriber at a later date (i.e. supply with an anticipated prescription). Decisions to supply and/or not supply related to medication type were more complex. For some cases, including medication with potential for abuse, the practice and/or the method of supply varied significantly according to age and gender of the pharmacist, and pharmacy location (p&lt;0.05). CONCLUSIONS: Although being a regular customer does not guarantee a supply, results of this study reinforce the importance for patients having a regular pharmacy, where pharmacists were more likely to continue medication supply in cases of patients presenting without a valid prescription. We would suggest, more flexible legislation should be implemented to allow pharmacists to continue supplying of medication when obtaining a prescription is not practical

Perioperative tumor cell dissemination in patients with primary or metastatic colorectal cancer

INTRODUCTION: Although there is general correlation between the TNM stage of colorectal cancer (CRC) and its prognosis, there is often significant variability of tumor behaviour and individual patient outcome, which is unaccounted for by pathologic factors alone. Our aim was to estimate perioperative tumor cell dissemination in patients with primary or CRC liver metastases as a possible factor influencing the outcome. METHODS: Forty patients were prospectively enrolled in the study from the year 2007 to 2008. Eighteen patients had histologically proven CRC (50% rectal, 44% colonic, 6% colonic and rectal). Sixteen patients (47%) had CRC liver metastases only. The remaining six patients who underwent colon or liver resection for benign conditions, acted as the control group. All patients with malignant pathologies had R0 resections. Blood samples were taken before the surgical incision (T0), immediately after tumor resection (T1) and at the end of the surgical intervention (T2). Data acquisition was performed using a dual-laser FACSCalibur flow cytometer. Circulating malignant cells were identified as being CD45-/cytokeratin+. RESULTS: The analysis of patients overall (CRC resection subgroup and hepatectomy subgroup) revealed that there was no statistically significant difference of the tumoral cell count in the blood per million of hematopoietic cells at T0, T1 and T2. CONCLUSIONS: This study demonstrates no differences in the detected circulating numbers of tumor cells at different stages of surgical intervention

Medication supply to residential aged care facilities in Western Australia using a centralized medication chart to replace prescriptions

<p>Abstract</p> <p>Background</p> <p>Current model of medication supply to R(RACFs) in Australia is dependent on paper-based prescriptions. This study is aimed at assessing the use of a centralized medication chart as a prescription-less model for supplying medications to RACFs.</p> <p>Methods</p> <p>Two separate focus groups were conducted with general practitioners (GPs) and pharmacists, and another three with registered nurses (RNs) and carers combined. All focus group participants were working with RACFs. Audio-recorded data were compared with field notes, transcribed and imported into NVivo® where it was thematically analyzed.</p> <p>Results</p> <p>A prescription-less medication chart model was supported and it appeared to potentially improve medication supply to RACF residents. Centralization of medication supply, clarification of medication orders and responding in real-time to therapy changes made by GPs were reasons for supporting the medication chart model. Pharmacists preferred an electronic version of this model. All health professionals cautioned against the need for GPs regularly reviewing the medication chart and proposed a time interval of four to six months for this review to occur. Therapy changes during weekends appeared a potential difficulty for RNs and carers whereas pharmacists cautioned about legible writing and claiming of medications dispensed according to a paper-based model. GPs cautioned on the need to monitor the amount of medications dispensed by the pharmacy.</p> <p>Conclusion</p> <p>The current use of paper prescriptions in nursing homes was identified as burdensome. A prescription-less medication chart model was suggested to potentially improve medication supply to RACF residents. An electronic version of this model could address main potential difficulties raised.</p

Use of postmenopausal hormone therapy and risk of Alzheimer's disease in Finland: nationwide case-control study

OBJECTIVESTo compare the use of hormone therapy between Finnish postmenopausal women with and without a diagnosis for Alzheimer's disease.DESIGNNationwide case-control study.SETTINGFinnish national population and drug register, between 1999 and 2013.PARTICIPANTSAll postmenopausal women (n= 84 739) in Finland who, between 1999 and 2013, received a diagnosis of Alzheimer's disease from a neurologist or geriatrician, and who were identified from a national drug register. Control women without a diagnosis (n= 84 739), matched by age and hospital district, were traced from the Finnish national population register.INTERVENTIONSData on hormone therapy use were obtained from the Finnish national drug reimbursement register.MAIN OUTCOME MEASURESOdds ratios and 95% confidence intervals for Alzheimer's disease, calculated with conditional logistic regression analysis.RESULTSIn 83 688 (98.8%) women, a diagnosis for Alzheimer's disease was made at the age of 60 years or older, and 47 239 (55.7%) women had been over 80 years of age at diagnosis. Use of systemic hormone therapy was associated with a 9-17% increased risk of Alzheimer's disease. The risk of the disease did not differ significantly between users of estradiol only (odds ratio 1.09, 95% confidence interval 1.05 to 1.14) and those of oestrogen-progestogen (1.17, 1.13 to 1.21). The risk increases in users of oestrogen-progestogen therapy were not related to different progestogens (noreth isterone acetate, medroxyprogesterone acetate, or other progestogens); but in women younger than 60 at hormone therapy initiation, these risk increases were associated with hormone therapy exposure over 10 years. Furthermore, the age at initiation of systemic hormone therapy was not a decisive determinant for the increase in risk of Alzheimer's disease. The exclusive use of vaginal estradiol did not affect the risk of the disease (0.99, 0.96 to 1.01).CONCLUSIONSLong term use of systemic hormone therapy might be accompanied with an overall increased risk of Alzheimer's disease, which is not related to the type of progestogen or the age at initiation of systemic hormone therapy. By contrast, use of vaginal estradiol shows no such risk. Even though the absolute risk increase for Alzheimer's disease is small, our data should be implemented into information for present and future users of hormone therapy