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Abstract Objective Women with type 2 diabetes experience higher cardiovascular and mortality risk than men possibly because of a sub-optimal cardio-protective treatment. We evaluated whether an intensive multifactorial therapy (MT) produces similar protective effect on development of adverse outcomes in women and men. Research design and methods Nephropathy in Diabetes type 2 study is an open-label cluster randomized trial comparing the effect of Usual Care (UC) or MT of main cardiovascular risk factors (blood pressure

Liposomes are spherical vesicles formed by a inner aqueous core and a double lipidic layer around it. Conventional techniques for the production of liposomes are characterized by several drawbacks, like the production of micrometric vesicles, a difficult control of the Particle Size Distribution (PSD) and low encapsulation efficiencies (EE) of hydrophilic compounds. Many supercritical semi-continuous techniques were proposed in literature. They are successful in the intent of producing liposomes of smaller diameter, but the EE of hydrophilic compounds and the reproducibility are still a challenge. For this reason, it was recently proposed a new supercritical process whose aim is to invert the steps of production of liposomes, by first creating water droplets and then to fast surround them by phospholipids. We discovered that the high diffusion coefficient of phospholipids in supercritical carbon dioxide allows a fast coverage of water droplets preserving the drug content into the liposome core. In this work, hydrophilic compounds were encapsulated in the vesicles produced using SuperLip, such as Fluorescein, Bovine Serum Albumin (BSA) and Ampicillin, obtaining monodispersed spherical vesicles with a mean size from 100 to 300 nm. Operative parameters like water flow rate and lipid to water mass ratio were optimized. The EEs were evaluated with UV-Vis spectroscopy according to methods reported in literature, and obtaining high values up to 99 % for the three investigated compounds.

The placenta, a temporary organ that forms during pregnancy, is the largest fetal organ and the first to develop. It is recognized as an organ that plays a vital role as a metabolic and physical barrier in the fetoplacental unit; throughout fetal development it acts as the lungs, gut, kidneys, and liver of the fetus. When its two components, the fetal and the maternal one, successfully interact, pregnancy proceeds healthily. However, in some cases there may be pregnancy disorders, such as preeclampsia (PE) and gestational diabetes mellitus (GDM), which can lead to a different outcome for the mother and the newborn. In recent years, several studies have been conducted to try to understand how the expression of factors involved in the development of the placenta varies under pathological conditions compared with normal conditions. The purpose of this review is to summarize recent discoveries in this field. [ABSTRACT FROM AUTHOR]

• Expanded Liquid composition is key parameter to control liposome size and distribution. • Successful control of liposomes at nanometric and micrometric level. • Reduction of solvent residue below FDA limits changing Expanded Liquid composition. Supercritical assisted Liposome formation process (SuperLip) allows one-shot, continuous and reproducible production of liposomes. In this work, the optimization of Gas to Liquid Ratio of the Expanded Liquid (GLR-EL); i.e., the ratio between carbon dioxide flow rate and ethanol flow rate, is presented. It allows to control liposomes diameter from micrometric to nanometric range and the amount of Solvent Residue (SR) in the final suspension. Working at a GLR-EL lower than about 1.8, resulted in the production of micrometric and sub-micrometric L-α-phosphatidylcholine (PC) liposomes, with mean diameters ranging from 1729 ± 733 nm to 878 ± 170 nm; whereas, working at larger GLRs-EL nanometric liposomes, with diameters down to about 139 ± 49 nm were produced. Liposomes produced at GLR-EL 6.0 were loaded with a hydrophilic compound: an antibiotic, vancomycin, or a lipophilic antioxidant, farnesol. Liposome diameters were again nanometric down to 126 ± 35 nm for farnesol loaded vesicles and encapsulation efficiencies (EE) were up to 76.7 ± 1.9%. The mean size of vancomycin loaded liposomes was 250 ± 93 nm and EE up to 74.0 ± 1.1% were obtained. SR down to 10 ppm were obtained on loaded vesicles, improving the possibility of their use for pharmaceutical applications. [ABSTRACT FROM AUTHOR]

Conventional techniques developed for the production of liposomes for ocular delivery show low encapsulation efficiencies (EE). In this work, a supercritical CO 2 based one-step continuous process, named Supercritical Assisted Liposome formation (SuperLip), was used for the production of liposomes to deliver ophthalmic antibiotics, such as ampicillin and ofloxacin. Micrometric and sub-micrometric liposomes with mean diameters in the range from 280 ± 104 nm to 1.76 ± 0.79 μm were successfully produced using drug concentrations in the range from 1% to 6% w/w and water to lipid ratios from 1.7 mg/g to 25 mg/g. Encapsulation efficiencies up to 97% and 99% were obtained for ofloxacin and ampicillin respectively. Storage stability and drug release kinetics of produced liposomes were also studied. Liposomes were stable for at least 3 months, with negligible drug leakage during storage time. At 37 °C ofloxacin and ampicillin were released in a controlled manner within 3 and 4 h respectively. [ABSTRACT FROM AUTHOR]

Liposomes are natural vesicles generally based on phosphatidylcholine (PC). The optimization of the lipid bilayer composition with the addition of little percentages of natural lipids is still at early stage due to the difficulties experienced by classical liposome formation processes, mainly, in reproducibility and encapsulation efficiency. Supercritical assisted liposome formation (SuperLip) has demonstrated that these limitations can be overcome. Therefore, in this work, this process has been tested to produce liposomes of controlled nanometric diameter and the effect of water solution flow rate on drug encapsulation efficiency was investigated. The addition of cholesterol (Chol) or phosphatidylethanolamine (PE) was also studied to gain the control on the release rate of the drug entrapped in liposomes. Theophylline was selected as the model hydrophilic drug. Using SuperLip process, PC/Chol and PC/PE liposomes were successfully produced with nanometric mean diameters down to 200 nm. Optimization of both lipid composition and SuperLip operative parameters allowed to obtain theophylline encapsulation efficiencies up to 98%. Drug release kinetics were affected by liposome composition, in particular, the addiction of Chol and PE allowed to slow down theophylline release rate. These results confirmed the possibility of producing liposomes with a complex architecture of the lipid membrane using the SuperLip process. [ABSTRACT FROM AUTHOR]

Spent automotive catalysts are industrial non-hazardous wastes of high added values because of the presence of platinum group metals, whose recovery is gaining increasing attention in European countries. This paper proposes a hydrometallurgical process to recover platinum from diesel catalysts, based on a first leaching step with aqueous solutions of H 2 O 2 (up to 0.2 M) and mild HCl concentrations (0.4 M), followed by a refining step in which platinum is deposited over a granular activated carbon. Tests were carried out at different H 2 O 2 content, temperatures, and sizes of granulated catalyst. The use of H 2 O 2 and low HCl content allows higher sustainability than conventional hydrometallurgical processes by reducing safety risks associated with the use of concentrated HCl and the emissions of NOx deriving from the use of nitrogen species in conventional leaching. Besides, the use of an adsorbent avoids the utilization of cyanides or other toxic organic solvents for the refining of the leaching solution. Experiments revealed that the low HCl concentration results in longer leaching times; however, process conditions can be tuned to completely recover platinum with negligible extraction of other metals on the catalyst, minimizing on the subsequent adsorption process. Optimal conditions appear as leaching at 20 °C with a 0.13 M H 2 O 2 0.4 M HCl solution followed by an adsorption step at 20 °C using an activated carbon with high BET surface area and high content of reducing surface groups. These findings suggest that the proposed recovery process can be a suitable candidate for future technology implementations. [Display omitted] • A leaching-adsorption process is proposed to solve a waste management issue. • Hydrogen peroxide is required to improve leaching at low temperatures. • Hydrogen peroxide is not needed at high temperatures. • 3.3% HCl, 1% v/v H2O2 at 90 °C solutions allows recovery 100% platinum in 3 h. • Pt adsorption is favored by lower temperatures on 1% H2O2 leached solutions. [ABSTRACT FROM AUTHOR]

The article examines the inotropic and lusitropic effects of nitroxyl (HNO) in myocardium through activation of sarcoplasmic reticulum ATPase (SERCA). Adult rat ventricular myocytes were exposed to HNO derived from Angeli's salt to illustrate the molecular mechanism. It was found that HNO increases the maximal activation of SERCA via S-glutathiolation at cysteine 674.

BACKGROUND: Nondipping status is associated with greater cardiovascular morbidity and mortality and faster progression of chronic kidney disease (CKD). We examined whether shifting 1 antihypertensive drug from morning to evening restores the circadian rhythm of blood pressure in nondipper patients with CKD. STUDY DESIGN: 8-week clinical trial without a control group. SETTING & PARTICIPANTS: We selected from our outpatient renal clinic 32 patients with CKD with estimated glomerular filtration rate less than 90 mL/min/1.73 m(2) and night-day ratio of mean ambulatory blood pressure (ABP) greater than 0.9, but with normal daytime ABP (<135/85 mm Hg) to avoid the required therapy intensification. INTERVENTION: Shifting 1 antihypertensive drug from morning to evening. OUTCOMES: Percentage of patients changing the night-day ratio of mean ABP from greater than 0.9 to 0.9 or less 8 weeks after the shift. MEASUREMENTS: Office blood pressure/ABP and proteinuria at baseline and after the shift. RESULTS: There were 55% men with a mean age of 67.4 +/- 11.3 years and estimated glomerular filtration rate of 46 +/- 12 mL/min/1.73 m(2). They were treated with 2.4 +/- 1.4 antihypertensive drugs. After the drug shift, the night-day ratio of mean ABP decreased in 93.7% of patients, with normal circadian rhythm restored in 87.5%. The nocturnal systolic and diastolic ABP decrease was not associated with an increase in diurnal ABP and was independent from number and class of shifted drug. Office blood pressure in the morning also decreased (from 136 +/- 16/77 +/- 10 to 131 +/- 13/75 +/- 8 mm Hg; P = 0.02). Urinary protein excretion decreased from 235 +/- 259 to 167 +/- 206 mg/d (P < 0.001). LIMITATIONS: Absence of a control group and patients with severe proteinuria or uncontrolled daytime ABP. CONCLUSIONS: In nondipper patients with CKD, changing the timing of antihypertensive therapy decreases nocturnal blood pressure and proteinuria.Copyright © 2007 by Elsevier Inc. [ABSTRACT FROM AUTHOR]

• Ampicillin loaded liposomes were entrapped in alginate aerogels to create a meta-carrier. • SuperLip favored the production of liposomes at nanometric level. • Alginate gel nanoporous structure was preserved by supercritical drying. • Ampicillin release time from meta-carriers was twice than its release from liposomes alone. Ampicillin loaded liposomes were entrapped in alginate aerogels to create a meta-carrier (a carrier within another carrier), to obtain a prolonged drug release. Liposomes with a diameter of 200 ± 77 nm and with an encapsulation efficiency of 69.5 ± 1.2% were produced using a supercritical assisted formation process (SuperLip). Then, they were entrapped into alginate gels, and the final loaded aerogels were obtained by supercritical CO 2 drying. The successful entrapment of liposomes into aerogels was confirmed by EDX analysis. Drug release tests demonstrated that ampicillin release time from these meta-carriers was about 4 days; i.e., about twice than its release time from liposomes alone. Two mass transfer resistances in series operated in the overall drug release: one related to liposomes lipidic layers and one due to the presence of the alginate aerogel matrix. [ABSTRACT FROM AUTHOR]

Biomaterials embody a groundbreaking paradigm shift in the field of drug delivery and human applications. Their versatility and adaptability have not only enriched therapeutic outcomes but also significantly reduced the burden of adverse effects. This work serves as a comprehensive overview of biomaterials, with a particular emphasis on their pivotal role in drug delivery, classifying them in terms of their biobased, biodegradable, and biocompatible nature, and highlighting their characteristics and advantages. The examination also delves into the extensive array of applications for biomaterials in drug delivery, encompassing diverse medical fields such as cancer therapy, cardiovascular diseases, neurological disorders, and vaccination. This work also explores the actual challenges within this domain, including potential toxicity and the complexity of manufacturing processes. These challenges emphasize the necessity for thorough research and the continuous development of regulatory frameworks. The second aim of this review is to navigate through the compelling terrain of recent advances and prospects in biomaterials, envisioning a healthcare landscape where they empower precise, targeted, and personalized drug delivery. The potential for biomaterials to transform healthcare is staggering, as they promise treatments tailored to individual patient needs, offering hope for improved therapeutic efficacy, fewer side effects, and a brighter future for medical practice.

Obesity is recognized as a true chronic disease and an independent risk factor for kidney disease. In particular, a correlation was observed between obesity and the development of focal segmental glomerulosclerosis. The clinical consequences of obesity on the kidney can include albuminuria, nephrotic syndrome, nephrolithiasis, and increased risk of development and progression of renal failure. Conventional therapy, which includes low-calorie diet, exercise, lifestyle changes, and drug therapy, including GLP1-RA, phentermine, phentermine/topiramate, bupropion/naltrexone, orlistat, is not always able to achieve the desired results and above all does not guarantee stabilization of body weight over time. On the other hand, bariatric surgery is giving excellent results in terms of efficacy and duration. Bariatric surgery techniques that are generally divided into restrictive, malabsorptive, and mixed are not free from possible metabolic complications such as anemia, vitamin deficiency, and stones. However, they are able to ensure a good maintenance of weight loss obtained with disappearance or reduction of the incidence and severity of comorbidities related to obesity., (Copyright by Società Italiana di Nefrologia SIN, Rome,Italy.)

Lipidic carriers are efficient vehicles preserving drugs during cell administration. Several production processes of lipidic nanoparticles were developed to reduce mean size at nanometric level, enhancing homogeneity and process replicability. However, lipidic aggregation has always been considered a huge drawback in terms of high polidispersity and instability. Looking at this problem from a different point of view, specific operating parameters were employed to produce Nanostructured Lipidic Carriers (NLC), whose structure simulates the complexity of cell barrier. NLC present high surface to volume ratio, and improved potential in terms of drug entrapment efficiency and bioavailability. In this work, NLCs were produced by studying the effect of process parameters, such as Drug to Lipid Ratio from 2:1-1:20 w/w. At macroscopic level, the NLCs produced showed these diameters distribution: D(10 %) from 85 nm to 6 µm, D(50 %) of about 10 µm and D(90 %) of about 31 µm. Encapsulation Efficiencies were measured from a minimum of 92.06 % to a maximum of 98.93 %, with mass yield included between 48.8 % and 99 %. Scanning Electron Microscope demonstrated the complexity of the shape of these NLCs, characterized by nanometric structures (100-500 nm) grab on Q10 "pillars" or adsorbed on lipidic external sheet., (Copyright © 2022. Published by Elsevier B.V.)

This work represents an overview on types of wounds according to their definition, classification and dressing treatments. Natural and synthetic polymeric wound dressings types have been analyzed, providing a historical overview, from ancient to modern times. Currently, there is a wide choice of materials for the treatment of wounds, such as hydrocolloids, polyurethane and alginate patches, wafers, hydrogels and semi-permeable film dressings. These systems are often loaded with drugs such as antibiotics for the simultaneous delivery of drugs to prevent or cure infections caused by the exposition of blood vessel to open air. Among the presented techniques, a focus on foams has been provided, describing the most diffused branded products and their chemical, physical, biological and mechanical properties. Conventional and high-pressure methods for the production of foams for wound dressing are also analyzed in this work, with a proposed comparison in terms of process steps, efficiency and removal of solvent residue. Case studies, in vivo tests and models have been reported to identify the real applications of the produced foams.

Background and objectives: Liposomal structures are artificial vesicles composed of one or several lamellae of phospholipids which surround an inner aqueous core. Given the amphoteric nature of phospholipids, liposomes are promising systems for drug delivery. The present review provides an updated synthesis of the main techniques for the production of liposomes for orthopedic applications, focusing on the drawbacks of the conventional methods and on the advantages of high pressure techniques. Materials and Methods: Articles published in any language were systematically retrieved from two major electronic scholarly databases (PubMed/MEDLINE and Scopus) up to March 2020. Nine articles were retained based on the "Preferred Reporting Items for Systematic Reviews and Meta-Analyses" (PRISMA) guidelines. Results: Liposome vesicles decrease the rate of inflammatory reactions after local injections, and significantly enhance the clinical effectiveness of anti-inflammatory agents providing controlled drug release, reducing toxic side effects. Conclusions: This review presents an update on the improvement in musculoskeletal ailments using liposome treatment.

Atypical hemolytic uremic syndrome (aHUS) is a rare and heterogenous disease caused by a disregulation of the alternative pathway of the complement cascade. Specifically, microvascular damage is produced that can lead to acute kidney disease, hemolytic anemia and thrombocytopenia. It accounts for 10% of all hemolytic uremic syndromes and can result in death or in end stage renal disease since the first episode. We can differentiate two forms of aHUS: a sporadic form (80%), affecting adult people, and a familial form (20%) that usually became manifest during infancy. In the acute phase of the disease, frequent and severe anemia requires multiple blood transfusions, exposing patients to the risk of catching an infective disease. HCV hepatitis is the most prevalent chronic hepatitis worldwide, with approximately 170 million chronically infected individuals - many of which are unaware of their condition. The evolution of the HCV infection is variable: almost 20% of patients spontaneously clear the infection over time (Anti HCV positive, HCV RNA negative patients); 80% of patients cannot control the virus and develop chronic infection (Anti HCV positive; HCV RNA positive patients) that can evolve into liver cirrhosis and hepatocellular carcinoma. The aim of this paper is to describe a clinical case of acute HCV hepatitis in a patient with aHUS treated with Eculizumab., (Copyright by Società Italiana di Nefrologia SIN, Rome, Italy.)

Supercritical Emulsion Extraction (SEE) and Supercritical assisted Liposome formation (SuperLip), use dense gases such as carbon dioxide (dCO 2 ) to fabricate advanced micro/nanocarriers. SEE uses dCO 2 to extract solvent from the oily phase of an emulsion and obtain biopolymer microbead; For this study, poly-Lactic Acid (PLA) microbeads of 1 ± 0.2 μm in mean size loaded at 1 µg/mg PLA with Rhodamine B (ROD) were prepared by SEE; the beads showed a solvent residue lower than 10 ppm and encapsulated the fluorochrome with an efficiency of 90%. SuperLip uses dCO2 to enhance lipid/ethanol/water mixing and to promote the ethanol extraction from liposome suspension. In this case, phosphatidyl-choline (PC) vesicles with a mean size of 0.2 ± 0.05 μm and loaded with Fluorescein Iso-ThioCyanate (FITC) at 8 µg/mg PC were prepared; small unilamellar structure was observed for all the vesicles with FITC encapsulation efficiency of 80%. Ethanol residue of 50 ppm was measured in all the liposome suspensions. The bioavailability of microbeads and nanoliposomes was assessed through incubation with human monocytes previously isolated from healthy donors' blood. A specifically optimized protocol that allowed their quenching on the cell surface was developed to monitor by flow cytometer assay only the cell population that effectively internalized the carriers. When microbeads were tested, the percentage of alive internalizing monocytes was of about 30%. An internalization of 96.1 ± 21% was, instead, obtained at dosage of 0.1 mg/mL for nanoliposomes. In this last case, monocytes showed a vitality of almost 100% after vesicles internalization at all the concentrations studied; on the other hand, cell apoptosis progressively increased in a dose/response manner, after polymer microbeads phagocytosis. The proposed data suggested that dCO 2 technologies can be reliably used to fabricate intracellular carriers., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Blood pressure (BP) is hardly controlled in chronic kidney disease (CKD). We compared the effect of very low protein diet (VLPD) supplemented with ketoanalogs of essential amino acids (0.35 g/kg/day), low protein diet (LPD, 0.60 g/kg/day), and free diet (FD) on BP in patients with CKD stages 4 and 5. Vegetable proteins were higher in VLPD (66%) than in LPD (48%). LPD was prescribed to 110 consecutive patients; after run-in, they were invited to start VLPD. Thirty subjects accepted; 57 decided to continue LPD; 23 refused either diet (FD group). At baseline, protein intake (g/kg/day) was 0.79+/-0.09 in VLPD, 0.78+/-0.11 in LPD, and 1.11+/-0.18 in FD (P<0.0001). After 6 months, protein intake was lower in VLPD than LPD and FD (0.54+/-0.11, 0.78+/-0.10, and 1.04+/-0.21 g/kg/day, respectively; P<0.0001). BP diminished only in VLPD, from 143+/-19/84+/-10 to 128+/-16/78+/-7 mm Hg (P<0.0001), despite reduction of antihypertensive drugs (from 2.6+/-1.1 to 1.8+/-1.2; P<0.001). Urinary urea excretion directly correlated with urinary sodium excretion, which diminished in VLPD (from 181+/-32 to 131+/-36 mEq/day; P<0.001). At multiple regression analysis (R2=0.270, P<0.0001), BP results independently related to urinary sodium excretion (P=0.023) and VLPD prescription (P=0.003), but not to the level of protein intake. Thus, in moderate to advanced CKD, VLPD has an antihypertensive effect likely due to reduction of salt intake, type of proteins, and ketoanalogs supplementation, independent of actual protein intake.

In the 1960s, about 10% of hemodialysis (HD) patients had hypertension; the current percentage of hypertensive patients has risen to 70-75%. The scarce implementation of low-salt diets and the increment of dialysate sodium concentration aimed at ameliorating treatment tolerability are the main causes of the currently poor hypertension control. Considerable sodium intake activates a vicious circle: an increase in serum osmolarity, greater thirst and greater water intake, high inter-dialytic weight gains, need for large ultrafiltration rates, more frequent episodes of intradialytic hypotension, failure to achieve dry weight, progressive extra-cellular volume (ECV) expansion, and finally, blood pressure (BP) increase. Therefore, many studies have pointed out the importance of a low-salt diet in HD; it has been proven that the normalization of BP and ECV overload with a low-salt diet is associated with left ventricular hypertrophy regression and diastolic dysfunction improvement. Preparing meals with fresh foods, using spices, avoiding salt when cooking, and drastically limiting salty foods reduce dietary sodium down to about 6 g/day. Sodium intake during inter-dialytic periods can easily be assessed by measuring the changes in serum sodium concentration and in body weight.