A Review: Uses of Chitosan in Pharmaceutical Forms.

Chitosan is a natural polysaccharide widespread in nature. It has many unique and attractive properties for the pharmaceutical field: it is biodegradable, safe, hypoallergenic, biocompatible with the body, free of toxicity, with proven anticholesterolemic, antibacterial, and antimycotic action. In this review we highlighted the physical, chemical, mechanical, mucoadhesive, etc. properties of chitosan to be taken into account when obtaining various pharmaceutical forms. The methods by which the pharmaceutical forms based on chitosan are obtained are very extensive, and in this study only the most common ones were presented.

Exploring a New Pathophysiological Association in Acne Vulgaris and Metabolic Syndrome: The Role of Biogenic Amines and Glutathione Peroxidase.

Background and Objectives: Metabolic disorders cause many skin issues, including acne vulgaris. This research investigated the function of glutathione peroxidase (GTPx) and biogenic amines as a potential novel pathophysiological link between metabolic syndrome (MetS) and acne vulgaris. Materials and Methods: The patients were distributed into two groups: metabolic precondition (MPG, n = 78) and control (CG, n = 81). To determine the extent of acne and metabolic preconditioning, patients were subjected to extensive clinical/paraclinical investigations. Additionally, catecholamine levels in urine and GTPx levels in blood were measured. Results: Mild acne was more common in the CG (32.1 vs. 6.4, p < 0.001), and severe acne was more common in the MPG (61.54 vs. 25.9, p < 0.001), with the average age being substantially higher in the MPG (23.81 vs. 21.05, p = 0.002). Significant variations were observed in the paraclinical levels for catecholamines (p < 0.05). In the MPG, most severe acne patients were overweight (52.1%), insulin-resistant (48.8%), or obese (47.9%). Moderate acne was most often linked to obesity (56%), overweight (44%), and insulin resistance (20%). Patients with severe acne (48.83%) had a considerably greater incidence of insulin resistance syndrome (p = 0.039) than those with moderate or severe acne (20%). The presence of two or three metabolic disorders considerably raised the risk of severe acne. Significant differences between groups were observed only in the subgroup of patients with severe acne, with lower values in the MPG (p = 0.015). Significant differences between groups were observed regarding the subgroup of patients with severe acne, with lower DTPx values in the MPG. At the group level, only CG patients with severe acne had reduced GTPx levels. Significant differences in catecholamine values were seen between groups (p < 0.05), independent of acne severity, except for adrenaline in mild acne patients (p = 0.059). Conclusions: The complex connection between GTPx and catecholamines in MetS suggests a significant role of these factors in the pathogenesis of acne associated with this condition, opening new perspectives in the research and treatment of acne in the context of MetS.

Sodium Alginate-Natural Microencapsulation Material of Polymeric Microparticles.

From the multitude of materials currently available on the market that can be used in the development of microparticles, sodium alginate has become one of the most studied natural anionic polymers that can be included in controlled-release pharmaceutical systems alongside other polymers due to its low cost, low toxicity, biocompatibility, biodegradability and gelatinous die-forming capacity in the presence of Ca2+ ions. In this review, we have shown that through coacervation, the particulate systems for the dispensing of drugs consisting of natural polymers are nontoxic, allowing the repeated administration of medicinal substances and the protection of better the medicinal substances from degradation, which can increase the capture capacity of the drug and extend its release from the pharmaceutical form.

In Vitro and Human Pilot Studies of Different Topical Formulations Containing Rosa Species for the Treatment of Psoriasis.

The aim of this study was to evaluate the phytochemical profile and antioxidant properties of the extracts from three Rosa species (R. canina, R. damascena, R. cairo), to develop and investigate topical formulations with lyophilized forms of extracts for the treatment of psoriasis. Phytochemical screening and in vitro total antioxidant capacity (DPPH, FRAP, CUPRAC, SOD) of studied samples were examined and compared. Lyophilized extracts of roses were dissolved in Transcutol HP and different formulations of creams were prepared. Franz diffusion method was used to evaluate the drug release and biocompatibility was tested on HaCaT cells. Rosa damascene had the best results regarding all the analyses that were conducted. After the evaluation of topical products, the formulation with Rosa damascena extract in a self-emulsifying drug delivery system was tested on a human clinical study that involved 20 patients. At the end of the clinical study an improvement in the quality of life of the patients was observed and erythema, induration and scaling were reduced. The present study indicates that our examined extracts exhibited great phenolic content, antioxidant capacity and safety profile of topical formulation and therefore can be used as a reliable source of natural antioxidants and may be used as a complementary treatment to improve the quality life of patients with psoriasis or may be tested on another diseases.

Topical Dosage Formulation of Lyophilized Philadelphus coronarius L. Leaf and Flower: Antimicrobial, Antioxidant and Anti-Inflammatory Assessment of the Plant.

Philadelphus coronarius is a versatile plant and its use in folk medicine has a long tradition; however, scientifically, the medical utilization of the herb is a less explored research field. The aim of our study was to identify and determine the quantity of the bioactive compounds of both the leaf and the flower and prepare a lyophilized product of them, from which medical ointments were formulated, since the topical application of P. coronarius has also not been studied. In vitro drug release, texture analysis and biocompatibility experiments were carried out, as well as the investigation of microbiological, antioxidant and anti-inflammatory properties. According to our results the composition and the selected excipients of the ointments have a great impact on the drug release, texture and bioavailability of the preparation. During the microbiological testing, the P. coronarius leaf was effective against Escherichia coli and Staphylococcus aureus, but it did not significantly decrease IL-4 production when it was tested on HaCaT cells. P. coronarius is a promising herb, and its topical application in antimicrobial therapy can be a useful addition to modern medical therapy.

Physalis alkekengi L. Extract Reduces the Oxidative Stress, Inflammation and Apoptosis in Endothelial Vascular Cells Exposed to Hyperglycemia.

To find new natural remedies in diabetes, this study investigated the biological activity of two extracts obtained from the fruits (PhyF) and herba (PhyH) of Physalis alkekengi var. franchetii L. on human umbilical vein endothelial cells (HUVECs) exposed to normo- and hyperglycemic conditions. The biological effect was quantified by malondialdehyde, IL-31 and IL-33 levels in correlation with physico-chemical characterization and antioxidant activity. Additionally, from PhyP extract, the caspase-3, IL-6, IL-10, tumor necrosis factor (TNF)-α and nuclear transcription factor NFkB expressions were evaluated. HPLC analysis revealed a significant number of phenolic compounds, especially in PhyF extract, with a good antioxidant activity as highlighted by TEAC, CUPRAC or DPPH methods. On HUVECS cells, the extracts were not toxic even at high concentrations. Particularly PhyF extract, diminished lipid peroxidation and inhibited the IL-31 and IL-33 secretions induced by hyperglycemia. The inhibitory effect on proinflammatory cytokines was noticed after both doses of PhyF extract in parallel with the upregulation of anti-inflammatory cytokine IL-10. Moreover, PhyF, especially in a low dose, reduced caspase-3 active form. These experimental findings suggest that Physalis fruits extract exerted beneficial effects in hyperglycemia by inhibition of oxidative stress, inflammation and apoptosis being a good adjuvant option in diabetes.

SIRT1 Activation by Equisetum Arvense L. (Horsetail) Modulates Insulin Sensitivity in Streptozotocin Induced Diabetic Rats.

BACKGROUND: Equisetum arvense L., commonly known as field horsetail is a perennial fern of which extracts are rich sources of phenolic compounds, flavonoids, and phenolic acids. Activation of SIRT1 that was shown to be involved in well-known signal pathways of diabetic cardiomyopathy has a protective effect against oxidative stress, inflammatory processes, and apoptosis that are the basis of diseases such as obesity, diabetes mellitus, or cardiovascular diseases. The aim of our study was to evaluate the antidiabetic and cardioprotective effects of horsetail extract in streptozotocin induced diabetic rats. METHODS: Diabetes was induced by a single intraperitoneal injection of 45 mg/kg streptozotocin. In the control groups (healthy and diabetic), rats were administered with vehicle, whilst in the treated groups, animals were administered with 50, 100, or 200 mg/kg horsetail extract, respectively, for six weeks. Blood glucose levels, glucose tolerance, and insulin sensitivity were determined, and SIRT1 levels were measured from the cardiac muscle. RESULTS: The horsetail extract showed moderate beneficial changes in blood glucose levels and exhibited a tendency to elevate SIRT1 levels in cardiomyocytes, furthermore a 100 mg/kg dose also improved insulin sensitivity. CONCLUSIONS: Altogether our results suggest that horsetail extract might have potential in ameliorating manifested cardiomyopathy acting on SIRT1.

Newborn screening in southeastern Europe.

The aim of our study was to assess the current state of newborn screening (NBS) in the region of southeastern Europe, as an example of a developing region, focusing also on future plans. Responses were obtained from 11 countries. Phenylketonuria screening was not introduced in four of 11 countries, while congenital hypothyroidism screening was not introduced in three of them; extended NBS programs were non-existent. The primary challenges were identified. Implementation of NBS to developing countries worldwide should be considered as a priority.

Comparative Study of Sperm Selection Techniques for Pregnancy Rates in an Unselected IVF-ICSI Population.

(1) Background: Semen analysis is a poor predictor of the fertilization potential of spermatozoa and a male factor may contribute to poor outcomes of the IVF procedure, despite a normal semen analysis. The microfluidic sperm selection (ZyMot-ICSI) is based on the selection of the spermatozoa with the lowest DNA fragmentation rate, but studies do not prove better clinical outcomes after this method. (2) Methods: We conducted a retrospective trial comparing 119 couples that were allocated to the classic gradient centrifugation sperm method (control group), and 120 couples that were allocated with the microfluidic technique being used (study group) at our university-level clinic, to go through IVF. (3) Results: The statistical analysis showed that there is no significant difference between the fertilization rate (study vs. control p = 0.87), but regarding blastocyst rate (study vs. control p = 0.046) and clinical pregnancy (p = 0.049), there is quite a significant statistical difference. Microfluidic preparation of spermatozoa seems to improve the results and it may be utilized more broadly for ICSI, and could also improve the workflow in standard IVF, decrease intervention by laboratory personnel and provide more consistent incubation conditions. (4) Conclusions: The patients that had the sperm preparation for ICSI with the microfluidic sperm selection had slightly better results compared with the gradient centrifugation selection.

The Role of Oxidative Stress in Infertility.

(1) Background: Oxidative stress markers in the follicular fluid and serum of the patient with IVF results (number of fertilized oocytes, number of embryos, cumulative pregnancy rate) are important in establishing the causes of infertility. (2) Methods: 42 patients were enrolled in the study over the duration of 24 months and were divided into two groups: the study group divided into the female etiology for infertility as a tubal factor, diminished ovarian reserve, endometriosis, and unexplained infertility, and the control group consisting of the male factor, excluding the sperm donors and with no female factor cause. On the day of ovarian puncture in IVF, follicular fluid and serum were collected from the patients. (3) Results: Malondialdehyde from the follicular fluid was higher in the control group. The total antioxidant capacity in the follicular fluid is positively correlated with the pregnancy rate. There is no statistically significant difference in the oxidative stress markers from serum in both groups. (4) Conclusions: The capacity of the follicular fluid environment to contain the reactive oxygen species (ROS) leads to a higher pregnancy rate in the control group.

Phytochemical Compounds Involved in the Bone Regeneration Process and Their Innovative Administration: A Systematic Review.

Bone metabolism is a complex process which is influenced by the activity of bone cells (e.g., osteocytes, osteoblasts, osteoclasts); the effect of some specific biomarkers (e.g., parathyroid hormone, vitamin D, alkaline phosphatase, osteocalcin, osteopontin, osteoprotegerin, osterix, RANKL, Runx2); and the characteristic signaling pathways (e.g., RANKL/RANK, Wnt/ß, Notch, BMP, SMAD). Some phytochemical compounds-such as flavonoids, tannins, polyphenols, anthocyanins, terpenoids, polysaccharides, alkaloids and others-presented a beneficial and stimulating effect in the bone regeneration process due to the pro-estrogenic activity, the antioxidant and the anti-inflammatory effect and modulation of bone signaling pathways. Lately, nanomedicine has emerged as an innovative concept for new treatments in bone-related pathologies envisaged through the incorporation of medicinal substances in nanometric systems for oral or local administration, as well as in nanostructured scaffolds with huge potential in bone tissue engineering.

Preparation and Characterization of Chitosan-Alginate Microspheres Loaded with Quercetin.

The aim of this paper was to formulate microspheres based on biodegradable polymers (chitosan and sodium alginate), using the complex coacervation technique. Subsequently, the prepared microspheres were loaded with quercetin (QUE), a pharmacological active ingredient insoluble in water and unstable to light, temperature and air. After preparation, the loaded microspheres underwent several studies for physical chemical characterization (performed by scanning electron microscopy-SEM, laser 3D scanning, and thermal analysis-TA). Furthermore, they were analyzed in order to obtain information regarding swelling index, drug entrapment, and in vitro release capacity. The obtained experimental data demonstrated 86.07% entrapment of QUE into the microspheres, in the case of the one with the highest Ch concentration. Additionally, it was proved that such systems allow the controlled release of the active drug over 24 h at the intestinal level. SEM micrographs proved that the prepared microspheres have a wrinkled surface, with compact structures and a large number of folds. On the basis of the TA analysis, it was concluded that the obtained microspheres were thermally stable, facilitating their usage at normal physiological temperatures as drug delivery systems.

Echinacea purpurea (L.) Moench: Biological and Pharmacological Properties. A Review.

Echinacea purpurea (L.) Moench (EP)is a perennial herbaceous flowering plant, commonly known as purple coneflower and it belongs to the Asteraceae family. The Echinacea genus is originally from North America, in the United States, and its species are widely distributed throughout. There are nine different species of Echinacea, but only three of them are used as medicinal plants with wide therapeutic uses: Echinacea purpurea (L.) Moench, Echinacea pallida (Nutt.) Nutt. and Echinacea angustifolia DC. Several significant groups of bioactive compounds with pharmacological activities have been isolated from Echinacea species. Numerous beneficial effects have been demonstrated about these compounds. The immunomodulatory effect was initially demonstrated, but over time other effects have also been highlighted. The present review gives a comprehensive summary of the chemical constituents, bioactive compounds, biological effects and therapeutical uses of purple coneflower. Research shows that such a well-known and recognized species needs to be further studied to obtain efficient products with a guarantee of the safety.

Metal Nanoparticles and Carbon-Based Nanomaterials for Improved Performances of Electrochemical (Bio)Sensors with Biomedical Applications.

Monitoring human health for early detection of disease conditions or health disorders is of major clinical importance for maintaining a healthy life. Sensors are small devices employed for qualitative and quantitative determination of various analytes by monitoring their properties using a certain transduction method. A "real-time" biosensor includes a biological recognition receptor (such as an antibody, enzyme, nucleic acid or whole cell) and a transducer to convert the biological binding event to a detectable signal, which is read out indicating both the presence and concentration of the analyte molecule. A wide range of specific analytes with biomedical significance at ultralow concentration can be sensitively detected. In nano(bio)sensors, nanoparticles (NPs) are incorporated into the (bio)sensor design by attachment to the suitably modified platforms. For this purpose, metal nanoparticles have many advantageous properties making them useful in the transducer component of the (bio)sensors. Gold, silver and platinum NPs have been the most popular ones, each form of these metallic NPs exhibiting special surface and interface features, which significantly improve the biocompatibility and transduction of the (bio)sensor compared to the same process in the absence of these NPs. This comprehensive review is focused on the main types of NPs used for electrochemical (bio)sensors design, especially screen-printed electrodes, with their specific medical application due to their improved analytical performances and miniaturized form. Other advantages such as supporting real-time decision and rapid manipulation are pointed out. A special attention is paid to carbon-based nanomaterials (especially carbon nanotubes and graphene), used by themselves or decorated with metal nanoparticles, with excellent features such as high surface area, excellent conductivity, effective catalytic properties and biocompatibility, which confer to these hybrid nanocomposites a wide biomedical applicability.

Comparative Study of the Pharmacological Properties and Biological Effects of Polygonum aviculare L. herba Extract-Entrapped Liposomes versus Quercetin-Entrapped Liposomes on Doxorubicin-Induced Toxicity on HUVECs.

This study aimed to evaluate the comparative biological effects of Polygonum aviculare L. herba (PAH) extract and quercetin-entrapped liposomes on doxorubicin (Doxo)-induced toxicity in HUVECs. HUVECs were treated with two formulations of liposomes loaded with PAH extract (L5 and L6) and two formulations of liposomes loaded with quercetin (L3 prepared with phosphatidylcholine and L4 prepared with phosphatidylserine). The results obtained with atomic force microscopy, zeta potential and entrapment liposome efficiency confirmed the interactions of the liposomes with PAH or free quercetin and a controlled release of flavonoids entrapped in all the liposomes. Doxo decreased the cell viability and induced oxidative stress, inflammation, DNA lesions and apoptosis in parallel with the activation of Nrf2 and NF-kB. Free quercetin, L3 and L4 inhibited the oxidative stress and inflammation and reduced apoptosis, particularly L3. Additionally, these compounds diminished the Nrf2 and NF-kB expressions and DNA lesions, principally L4. PAH extract, L5 and L6 exerted antioxidant and anti-inflammatory activities, reduced γH2AX formation and inhibited extrinsic apoptosis and transcription factors activation but to a lesser extent. The loading of quercetin in liposomes increased the cell viability and exerted better endothelial protection compared to free quercetin, especially L3. The liposomes with PAH extract had moderate efficiency, mainly due to the antioxidant and anti-inflammatory effects and the inhibition of extrinsic apoptosis.

Antimicrobial activity of fusidic acid inclusion complexes.

OBJECTIVES: To synthesize and characterize the inclusion complexes of fusidic acid with ß - cyclodextrin, followed by the evaluation of their antimicrobial activity against pure strain (Staphylococcus aureus ATCC 25,923) and isolated Staphylococcus from clinical cases. METHODS: The desired compounds were synthesized using molar ratio of fusidic acid: ß-cyclodextrin of 1:1. Synthesized compounds were analyzed by Fourier Transform Infrared Spectroscopy (FTIR), X-Ray Diffraction (XRD), Scanning Electron Microscopy (SEM), and Thermal Analysis, and the results confirmed the formation of inclusion compounds by fusidic acid with ß-cyclodextrin. RESULTS: Physical-chemical characterization confirmed the preparation of desired inclusion compounds, and the antimicrobial test confirmed that all compounds obtained have antimicrobial activity. Antimicrobial activity of freeze-drying complex againstS. aureus is similar with pure fusidic acid activity, being better than the cefoxitin one. Similar behavior was observed against methicillin-resistant S. aureus and S. epidermidis. CONCLUSIONS: In the present work, three different inclusion complexes of fusidic acid were prepared using three different preparation methods. All inclusion complexes obtained presented good antimicrobial activity against differentS. aureus strains. Antimicrobial activity of these new prepared compounds was observed to be better than that of cefoxitin.

A Phytocomplex Consisting of Tropaeolum majus L. and Salvia officinalis L. Extracts Alleviates the Inflammatory Response of Dermal Fibroblasts to Bacterial Lipopolysaccharides.

BACKGROUND: The antimicrobial activity and effects of a phytocomplex consisting of Tropaeolum flos (T) and Salviae folium (S) extracts on the cytokine levels and transcription factors on dermal fibroblast BJ exposed to bacterial lipopolysaccharides were examined. METHODS: In order to select the most optimal combination ratio of the two extracts for using in vitro, the physicochemical characterization of vegetal extract mixtures was performed and the antioxidant and antibacterial activities were evaluated on five different formulations of T : S, namely, 1 : 1, 1 : 2, 2 : 1, 3 : 1, and 1 : 3. The best combination of bioactive compounds with regard to antioxidant and antibacterial activities (T : S 1 : 2) was selected for in vitro evaluation of the anti-inflammatory effect. Human dermal fibroblast BJ cells were treated with two doses of the extract mixture and then exposed to bacterial lipopolysaccharides (LPS). The levels of the cytokines involved in inflammatory response, namely, interleukin- (IL-) 6, tumor necrosis factor- (TNF-) α, IL-31, and IL-33, were quantified by ELISA, and the expression of transcription factors, namely, signal transducer and activator of transcription (STAT) 3, nuclear factor kappa B (NFκB), and phosphorylated NFκB (pNFκB), were evaluated by western blot analysis. RESULTS: The results have shown that the mixture of T : S 1 : 2 exhibited significant antibacterial effects on Staphylococcus aureus ATCC 25923. LPS exposure increased the cytokine levels in BJ cells and enhanced the NFκB expression. The pretreatment of BF cells exposed to LPS with the two doses of the extract mixture markedly inhibited the increase of IL-33 and TNF-α levels and amplified the NFκB expression and its activation, especially with the high dose. The low doses of the extract reduced NFκB expression but increased its activation. CONCLUSIONS: These experimental findings suggest that the mixture of T : S 1 : 2 can exert some protection against bacterial infections and inflammation induced by LPS in BJ cells being a good therapeutic option in related conditions associated with inflammation.

Ultrastructural modifications at the level of marginal periodontium in the case of incorrect dental reconstruction.

Our study focused on the evolution of the marginal periodontium inflammatory process caused by an incorrect dental reconstruction. Our research studied a control group and a group of patients having traumatic and inflammatory lesions in different stages of evolution. A pronounced rarefaction of the junction desmosome structures as well as an inflammatory process pointed out by the presence of macrophages, neutrophils, Langerhans' cells, and mastocytes. The presence of altered fibroblasts and collagen fibers in the electron microscopic sections of vascular lesions represents microscopic signs of the inflammation and support the theory of local immunoglobulin synthesis.

Recent Advances in Investigation, Prevention, and Management of Healthcare-Associated Infections (HAIs): Resistant Multidrug Strain Colonization and Its Risk Factors in an Intensive Care Unit of a University Hospital.

Active screening for resistant multidrug strain carriers remains an important component of infection control policy in any healthcare setting indifferent of financial and logistical costs. The objective of our study was to determine the spectrum of bacterial colonization individually among intensive care unit patients. A retrospective observational study was performed in the Intensive Care Unit of Emergency Clinical County Hospital of Oradea during 2017. Medical records of the patients were used for evaluation of source of ICU admission, previous antibiotic therapy, comorbidities, and length of hospital stay. Nasal and groin swabs for MRSA detection and rectal swabs for ESBL, VRE, and CRE detection were collected upon ICU admission of all patients in the first 24 hours and after 7 days. Swab samples were processed for isolation and identification of these resistant multidrug strains. Bacterial colonization on admission was detected in a quarter of patients included in the study. Carbapenemase-producing bacteria were the most common colonizers (21.16%). On admission, 12.06% of patients have been colonized by ESBL-producing members of the family Enterobacterales. Risk factors for colonization on admission to the ICU were chronic liver diseases and chronic renal failure for ESBL infection and chronic liver disease for CRE in male patients. Evaluation of Carmeli's score for male patients showed association only with CRE colonization. Chronic renal failure was found as risk factor for ESBL colonization in female patients. The prevalence of MRSA was 5.23% and less than 1% for VRE. There was no association between any risk factors studied and the presence of S. aureus or VRE upon admission. The 7-day ICU stay also proved to be an increased risk for ESBL and CRE infection.

Equisetum arvense L. Extract Induces Antibacterial Activity and Modulates Oxidative Stress, Inflammation, and Apoptosis in Endothelial Vascular Cells Exposed to Hyperosmotic Stress.

BACKGROUND: The antimicrobial activity of the Equisetum arvense L. extract and the mechanisms involved in the in vitro effects on endothelial vascular cells exposed to hyperosmotic stress were evaluated. METHODS: Antimicrobial activity was evaluated by disk diffusion method and minimum inhibitory concentration (MIC) determination, and oxidative stress, inflammation, and apoptosis, in pretreatment with Equisetum arvense L., caffeic acid, and cathechin, were quantified. RESULTS: The results have shown that Equisetum arvense L. exhibited antibacterial effects only on pathogenic gram-positive cocci. The modulatory activity of Equisetum arvense L. on endothelial cells exposed to hypertonic medium was different and depended on the concentration used. Low concentrations of tested compounds exerted antioxidant effect and diminished the activity of caspase-8 and also increased IκB expression while in high doses, Equisetum arvense L. was prooxidant, induced apoptosis, and decreased IL-6 secretion. CONCLUSIONS: These experimental findings suggest that Equisetum arvense L. has antibacterial effects on gram-positive cocci and, administered in low dose, may be a new therapeutic approach for diseases associated with hypertonic conditions or oxidative stress and apoptosis.