Modified denatured lysozyme effectively solubilizes fullerene c60 nanoparticles in water

Fullerenes, allotropic forms of carbon, have very interesting pharmacological effects and engineering applications. However, a very low solubility both in organic solvents and water hinders their use. Fullerene C60, the most studied among fullerenes, can be dissolved in water only in the form of nanoparticles of variable dimensions and limited stability. Here the effect on the production of C60 nanoparticles by a native and denatured hen egg white lysozyme, a highly basic protein, has been systematically studied. In order to obtain a denatured, yet soluble, lysozyme derivative, the four disulfides of the native protein were reduced and exposed cysteines were alkylated by 3-bromopropylamine, thus introducing eight additional positive charges. The C60 solubilizing properties of the modified denatured lysozyme proved to be superior to those of the native protein, allowing the preparation of biocompatible highly homogeneous and stable C60 nanoparticles using lower amounts of protein, as demonstrated by dynamic light scattering, transmission electron microscopy and atomic force microscopy studies. This lysozyme derivative could represent an effective tool for the solubilization of other carbon allotropes

Metformin: an inexpensive and effective treatment in people with diabetes and COVID-19?

Metformin: an inexpensive and effective treatment in people with diabetes and COVID-19? Comment

Insulin degludec/insulin aspart combination for the treatment of type 1 and type 2 diabetes

Glycemic control remains the major therapeutic objective to prevent or delay the onset and progression of complications related to diabetes mellitus. Insulin therapy represents a cornerstone in the treatment of diabetes and has been used widely for achieving glycemic goals. Nevertheless, a large portion of the population with diabetes does not meet the internationally agreed glycemic targets. Moreover, insulin treatment, especially if intensive, may be associated with emergency room visits and hospitalization due to hypoglycemic events. Therefore, fear of hypoglycemia or hypoglycemic events represents the main barriers to the attainment of glycemic targets. The burden associated with multiple daily injections also remains a significant obstacle to initiating and maintaining insulin therapy. The most attractive insulin treatment approach should meet the patients' preference, rather than demanding patients to change or adapt their lifestyle. Insulin degludec/insulin aspart (IDegAsp) is a new combination, formulated with ultra-long-acting insulin degludec and rapid-acting insulin aspart, with peculiar pharmacological features, clinical efficacy, safety, and tolerability. IDegAsp provides similar, noninferior glycemic control to a standard basal-bolus regimen in patients with type 1 diabetes mellitus, with additional benefits of significantly lower episodes of hypoglycemia (particularly nocturnal) and fewer daily insulin injections. Moreover, although treatment strategy and patients' viewpoint are different in type 1 and type 2 diabetes, trial results suggest that IDegAsp may be an appropriate and reasonable option for initiating insulin therapy in patients with type 2 diabetes inadequately controlled on maximal doses of conventional oral agents. This paper will discuss the role of IDegAsp combination as a novel treatment option in diabetic patients. © 2014 Dardano et al

Optimal therapy of type 2 diabetes: a controversial challenge

Type 2 diabetes mellitus (T2DM) is one of the most common chronic disorders in older adults and the number of elderly diabetic subjects is growing worldwide. Nonetheless, the diagnosis of T2DM in elderly population is often missed or delayed until an acute metabolic emergency occurs. Accumulating evidence suggests that both aging and environmental factors contribute to the high prevalence of diabetes in the elderly. Clinical management of T2DM in elderly subjects presents unique challenges because of the multifaceted geriatric scenario. Diabetes significantly lowers the chances of "successful" aging, notably it increases functional limitations and impairs quality of life. In this regard, older diabetic patients have a high burden of comorbidities, diabetes-related complications, physical disability, cognitive impairment and malnutrition, and they are more susceptible to the complications of dysglycemia and polypharmacy. Several national and international organizations have delivered guidelines to implement optimal therapy in older diabetic patients based on individualized treatment goals. This means appreciation of the heterogeneity of the disease as generated by life expectancy, functional reserve, social support, as well as personal preference. This paper will review current treatments for achieving glycemic targets in elderly diabetic patients, and discuss the potential role of emerging treatments in this patient population

Mild Thyroid Deficiency in the Elderly

no abstract availabl

Review of the clinical evidence for interferon β 1a (Rebif®) in the treatment of multiple sclerosis

Interferon (INF) β 1a 22 or 44 μg (Rebif®) administered s.c. 3 times a week (t.i.w) is a well established immunomodulating treatment for relapsing remitting multiple sclerosis (RRMS). This review focuses on its mechanisms of action, evidence of efficacy, safety, and tolerability. Several pharmacodynamic properties explain the immunomodulatory actions of INF β 1a 22 or 44 μg s.c. t.i.w. Pivotal trials and post-marketing studies proved that the drug is effective in reducing disease activity and likely in slowing disease progression. Head-to-head comparative studies with other marketed INFs β in RRMS suggested a better therapeutic response associated with higher doses and frequency of administration of Rebif®. Additional evidence indicated a beneficial effect of INF β 1a in patients with clinically isolated syndromes (CIS) suggestive of MS, as treatment reduced time to conversion to clinically definite (CD) disease. Further, although the drug did not prove to slow time to progression there were benefits on relapse- and MRI-related secondary outcome measures in secondary progressive (SP) MS. Pivotal trials, their cross-over extensions, and post-marketing studies consistently showed that INF β 1a 22 or 44 μg s.c. t.i.w. is safe and well tolerated, as adverse drug reactions are usually mild and manageable

Efficacy and safety of once-weekly semaglutide monotherapy in a young subject with Prader-Willi syndrome, obesity, and type 2 diabetes: a case report

BackgroundThe treatment of obesity and type 2 diabetes (T2D) in Prader-Willi syndrome (PWS) is still a challenge. Glucagon-like peptide 1 receptor agonists (GLP-1 RA) are attractive options, since they effectively reduce weight and improve blood glucose, without increasing the risk of hypoglycemia. However, data on their use in PWS are scarce.Case descriptionIn 2019, a 27-year-old male came to our Clinic because of first appearance of severe hyperglycemia (fasting plasma glucose 22.5 mmol/L). Based on clinical presentation, PWS was suspected, and diagnosis was confirmed by genetic tests. The patient was discharged on a basal-bolus insulin therapy managed by his parents due to his cognitive impairment. In spite of COVID-19 pandemic, the patient achieved tight glycemic control (HbA1c 41 mmol/mol) with non-severe hypoglycemic events in the face of significant body weight (BW) increase (+ 13 kg vs baseline). Insulin therapy was then discontinued, and once-weekly semaglutide (up to 0,5 mg weekly) was started. At 12-month follow-up, BW dropped from 79 to 73 kg while maintaining excellent glycemic control (HbA1c 40 mmol/mol). At 24-month follow-up, glycemic control remained optimal (HbA1c 38 mmol/mol) with further BW reduction (71 kg). Neither hypoglycemia nor gastro-intestinal or psychiatric adverse events were reported.ConclusionThis case supports the potential use of semaglutide for the treatment of subjects with PWS, obesity and T2D. Ad hoc trials are needed to evaluate the long-term efficacy and tolerability in these subjects

Effect of fasting on short-term visual plasticity in adult humans

Brain plasticity and function is impaired in conditions of metabolic dysregulation, such as obesity. Less is known on whether brain function is also affected by transient and physiological metabolic changes, such as the alternation between fasting and fed state. Here we asked whether these changes affect the transient shift of ocular dominance that follows short-term monocular deprivation, a form of homeostatic plasticity. We further asked whether variations in three of the main metabolic and hormonal pathways affected in obesity (glucose metabolism, leptin signalling and fatty acid metabolism) correlate with plasticity changes. We measured the effects of 2 h monocular deprivation in three conditions: post-absorptive state (fasting), after ingestion of a standardised meal and during infusion of glucagon-like peptide-1 (GLP-1), an incretin physiologically released upon meal ingestion that plays a key role in glucose metabolism.We found that short-term plasticity was less manifest in fasting than in fed state, whereas GLP-1 infusion did not elicit reliable changes compared to fasting. Although we confirmed a positive association between plasticity and supraphysiological GLP-1 levels, achieved by GLP-1 infusion, we found that none of the parameters linked to glucose metabolism could predict the plasticity reduction in the fasting versus fed state. Instead, this was selectively associated with the increase in plasma beta-hydroxybutyrate (B-OH) levels during fasting, which suggests a link between neural function and energy substrates alternative to glucose. These results reveal a previously unexplored link between homeostatic brain plasticity and the physiological changes associated with the daily fast-fed cycle