Multifunctional scaffolds for biomedical applications: Crafting versatile solutions with polycaprolactone enriched by graphene oxide.

The pressing need for multifunctional materials in medical settings encompasses a wide array of scenarios, necessitating specific tissue functionalities. A critical challenge is the occurrence of biofouling, particularly by contamination in surgical environments, a common cause of scaffolds impairment. Beyond the imperative to avoid infections, it is also essential to integrate scaffolds with living cells to allow for tissue regeneration, mediated by cell attachment. Here, we focus on the development of a versatile material for medical applications, driven by the diverse time-definite events after scaffold implantation. We investigate the potential of incorporating graphene oxide (GO) into polycaprolactone (PCL) and create a composite for 3D printing a scaffold with time-controlled antibacterial and anti-adhesive growth properties. Indeed, the as-produced PCL-GO scaffold displays a local hydrophobic effect, which is translated into a limitation of biological entities-attachment, including a diminished adhesion of bacteriophages and a reduction of E. coli and S. aureus adhesion of ∼81% and ∼69%, respectively. Moreover, the ability to 3D print PCL-GO scaffolds with different heights enables control over cell distribution and attachment, a feature that can be also exploited for cellular confinement, i.e., for microfluidics or wound healing applications. With time, the surface wettability increases, and the scaffold can be populated by cells. Finally, the presence of GO allows for the use of infrared light for the sterilization of scaffolds and the disruption of any bacteria cell that might adhere to the more hydrophilic surface. Overall, our results showcase the potential of PCL-GO as a versatile material for medical applications.

[Intra-arterial diazepam. Treatment and evolution of a case]. / Diazepam endoarteria. Trattamento ed evoluzione di un caso.

The Authors report a case of accidental self-administration of diazepam (valium) in the brachial artery by a drug addict and describe the developments, the sequelae and the pathogenetic mechanism.

Interactions of nucleic acids with distamycins. Binding of Dst-3 to d(CGTTTAAACG)2 and d(CGTACGTACG)2.

The binding between Distamycin 3 and the palindromic duplexes d(CGTTTAAACG)2 and d(CGTACGTACG)2 was investigated by two independent techniques: UV-Vis absorption in the Job's plot approach and Induced Circular Dichroism. Both decamers bind two molecules of peptide per duplex, with close overall affinities. This result indicates that a row of six A:T base pairs can accommodate two molecules of drug and that the minimal binding site of Distamycin 3 can consist of just two A:T base pairs.

Interactions of nucleic acids with distamycins. The drug monomeric chromophore.

A study of the monomeric chromophore of the oligopeptides netropsin (1), distamycin III (2), and distamycin V (3) by polarization spectroscopy techniques and molecular orbital calculations is reported. Linear dichroism spectra of the monomeric model compounds 1-methyl-2(ethylcarbamoyl)-4-acetamido-pyrrole (4) and 1-methyl-2(ethylcarbamoyl)-pyrrole (5) dissolved and oriented in lyotropic and thermotropic liquid crystals provide, together with the magnetic CD spectra, experimental checks of the theoretical calculations. The polarization directions of the investigated transition obtained by these means in this study allow us to build up in the following paper the exciton states of (1)-(3) and these provide a stereochemical interpretation of the flow linear dichroism spectra of the complexes of DNA with (2) and (3).

Linear dichroism studies of the complexes between CT-DNA and distamycins.

The study of the monomeric chromophore of the distamycins reported in Ref. 1 was used here to build up a description of the electronic states of the whole oligopeptide by the exciton theory. Liquid crystal-linear dichroism (LC-LD) spectra of the distamycins were recorded by using as orienting solvents both thermotropic and lyotropic mesomorphic media. The agreement between the LD spectra and the polarization assignments by the exciton treatment is satisfactory. On this basis the flow-LD spectra of the complex between distamycin V and DNA was interpreted in terms of the preferred relative orientations of the guest and host molecules. A single site location of the distamycin within the minor groove does not perfectly match the experimental order parameters. This orientational distribution function could be too simple to explain the experimental data. It may therefore be assumed that a small fraction of the guest molecules are preferentially aligned more parallel to the host chain axis than the minor groove. Alternatively, and probably more likely, the partial mismatch of the experimental data with the minor groove location may be seen as a manifestation of the well-known stiffening and bending effects at the binding sites, which have already been observed by other techniques.

Evidence for a prostaglandin-mediated bone resorptive mechanism in subjects with fasting hypercalciuria.

This study was performed to assess whether treatment with prostaglandin synthesis inhibitors decreases calcium excretion in patients with idiopathic hypercalciuria. Nineteen hypercalciuric (12 with fasting hypercalciuria (FH), 7 with nonfasting hypercalciuria (NFH) and 8 control non-hypercalciuric stone formers were treated with sodium diclofenac, 50 mg t.i.d. for 2 weeks. After a washout phase, 7 FH patients received 200 mg/day of sulindac (a nonsteroidal antiinflammatory agent (NSAID) inactive on renal prostaglandin synthetase) for 14 more days. Diclofenac reduced urine calcium excretion in subjects with idiopathic hypercalciuria with either normal or elevated fasting urinary calcium (from 387 +/- 26 to 240 +/- 23 mg/day, P less than 0.001; and from 370 +/- 39 to 246 +/- 40 mg/day, P less than 0.05, respectively), whereas it was ineffective in normocalciuric stone formers. Similar antihypercalciuric effectiveness was exerted by sulindac in the seven FH patients. The antihypercalciuric action exerted by diclofenac in subjects with FH was associated with a significant increment in serum PTH (48 +/- 4 vs, 70 +/- 9 pmol/liter, P less than 0.05), whereas in NFH subjects, the antihypercalciuric effect of diclofenac on NFH was not associated with a change in parathyroid activity. Since the major effect of NSAIDs is to decrease prostaglandin synthesis, these data suggest that prostaglandins may play a pathogenetic role in idiopathic hypercalciuria. Furthermore, they suggest that PTH is suppressed in patients with FH, possibly due to stimulation of prostaglandin-mediated bone resorption process.

The effects of calcitonin on idiopathic nephrolithiasis. Evidence of bone involvement in fasting hypercalciuria.

This study was performed to evaluate the antihypercalciuric effect of calcitonin (CT), a potent inhibitor of bone osteoclastic activity, on idiopathic hypercalciuria (IH). Forty-two stone formers were studied: 18 suffered from fasting hypercalciuria (FH), 12 from nonfasting hypercalciuria (NFH) and 12 were normocalciuric stone formers (NSF). All patients received CT, 25 U/day sc for a period of 15 days. CT caused a statistically significant drop in urine calcium, phosphorus and hydroxyproline (OH-proline) excretion in FH patients and a concomitant increase in serum PTH levels. In this group the percentage variation (D%) of urine calcium decrease was linearly correlated with D% decrease in urine OH-proline. These results support the hypothesis that pathological bone reabsorption might be involved in the genesis of FH.

Effects of beta non-selective and beta 1 selective adrenergic blocking agents on glucagon secretion from isolated perfused rat pancreas.

To characterize beta-receptors which affect pancreatic A-cell activity, the effects of propranolol (beta non-selective blockade) and metoprolol (beta 1 selective blockade) were evaluated on epinephrine modulated insulin (IRI) and glucagon (IRG) release both in basal state and during metabolic stimulus (arginine 20 mM). The isolated perfused rat pancreas model with the exclusion of stomach and duodenum was used. Epinephrine infusion (at 10(-7) M) caused a prompt and sustained increase in basal IRG secretion and significantly potentiated glucagon release in response to metabolic stimulus. Insulin secretion was markedly suppressed by epinephrine both in basal conditions and during metabolic stimulus. Propranolol (at 10(-7) M) and metoprolol (at 10(-7) M) infusion clearly and similarly counteracted epinephrine stimulatory effects on IRG secretion but failed to elicit any significant effect on the epinephrine inhibited IRI release either in basal state or during the metabolic stimulus. These results suggest that, at least in the rat, the adrenergic stimulation of IRG release is mediated through a beta 1 receptor.