Effects of gold nanoparticles phytoreduced with Cornus mas L. extract on the aorta wall function in rats with hyperlipid diet - a study on isolated aortic rings.

Background: Vascular reactivity may be influenced by the dysfunction of the perivascular adipose tissue (PVAT) that occurs after a prolonged high fat diet (HFD). Aim: The aim of this study was to investigate the vascular responses in rats with prolonged HFD after the administration of Cornus mas L. extract as a simple solution or as a reducing agent for gold nanoparticles (AuNPs). Methods: Sprague-Dawley adult female rats (21 animals) were randomly allocated into three groups (n=7) and received for 9 months hyperlipid diet, the last month with treatment administered through oral gavage, 0.5 mL/day of solution as follows: HFD group - 0.9% saline solution, HFD+CM group - Cornus mas L. extract (0.158 mg/mL polyphenols), HFD+AuNPsCM group - gold nanoparticles phytoreduced with Cornus mas L. extract (AuNPsCM, 260 µg Au/kg/day). The Control group of rats (n=7) was fed with standard diet and in the last month received 0.9% saline solution as treatment. At the end of the experiment, the rats' descending aortas were collected and were used to investigate the aorta wall responses to vasoconstrictor (phenylephrine) and vasodilator (acetylcholine) substances added in tissue bath. Results: AuNPsCM administration, compared to Control and HFD groups, increased the contraction and reduced the relaxation in aorta rings of rats with prolonged high-fat diet. The simple solution of Cornus mas L. extract produced contractile responses similar to those recorded in the Control group, at lower levels than in HFD group, and relaxation responses significantly decreased in comparison with Control group and significant increased when compared to HFD group. Conclusions: Cornus mas L. extract administered as simple solution improved the aorta functions, while AuNPsCM solution enhanced the existed aorta wall modifications occurred after prolonged HFD, altering the vessel wall responses.

The Beneficial Effect of Swimming Training Associated with Quercetin Administration on the Endothelial Nitric Oxide-Dependent Relaxation in the Aorta of Rats with Experimentally Induced Type 1 Diabetes Mellitus.

Type 1 diabetes mellitus is related to the vascular oxidative and nitrosative stress, the trigger for atherosclerosis and cardiovascular complications. The effects of moderate swimming training associated with quercetin oral administration were evaluated in aorta of rats with experimentally induced type 1 diabetes mellitus (T1DM), by analysing the nitric oxide-endothelial dependent relaxation (NO-EDR). T1DM rats received daily quercetin 30 mg/kg and followed the protocol of 5-weeks swimming exercise (30 min/day; 5 days/week). Aorta relaxation to acetylcholine (Ach) and sodium nitroprusside (SNP) were measured at the end of the experiment. Ach-induced endothelial dependent relaxation was significantly decreased in phenylephrine (PE) pre-contracted aorta of diabetic rats. Swimming exercise with quercetin administration preserved Ach-induced EDR but did not have any impact on SNP-induced endothelium-independent relaxation in the diabetic aorta. These findings suggest that quercetin administration associated with moderate swimming exercise could improve the endothelial NO-dependent relaxation in the aorta of rats with experimentally induced type 1 diabetes mellitus, showing that this therapeutical combination may improve and even prevent the vascular complications that occur in diabetic patients.

Effects of Gold Nanoparticles Functionalized with Cornus mas L. Fruit Extract on the Aorta Wall in Rats with a High-Fat Diet and Experimental-Induced Diabetes Mellitus-An Imaging Study.

Diabetes mellitus and high-fat diets trigger the mechanisms that alter the walls of blood vessels. Gold nanoparticles, as new pharmaceutical drug delivery systems, may be used in the treatment of different diseases. In our study, the aorta was investigated via imaging after the oral administration of gold nanoparticles functionalized with bioactive compounds derived from Cornus mas fruit extract (AuNPsCM) in rats with a high-fat diet and diabetes mellitus. Sprague Dawley female rats that received a high-fat diet (HFD) for 8 months were injected with streptozotocin to develop diabetes mellitus (DM). The rats were randomly allocated into five groups and were treated, for one additional month with HFD, with carboxymethylcellulose (CMC), insulin, pioglitazone, AuNPsCM solution or with Cornus mas L. extract solution. The aorta imaging investigation consisted of echography, magnetic resonance imaging and transmission electron microscopy (TEM). Compared to the rats that received only CMC, the oral administration of AuNPsCM produced significant increases in aorta volume and significant decreases in blood flow velocity, with ultrastructural disorganization of the aorta wall. The oral administration of AuNPsCM altered the aorta wall with effects on the blood flow.

Effects of Gold Nanoparticles Functionalized with Bioactive Compounds from Cornus mas Fruit on Aorta Ultrastructural and Biochemical Changes in Rats on a Hyperlipid Diet-A Preliminary Study.

Cornus mas L. extract (CM) presents hypolipidemic, antioxidant and anti-inflammatory activity. Gold nanoparticles (AuNPs) are considered potent delivery systems and may be used to release pharmaceutical compounds at the level of injury. In our study, we used gold nanoparticles functionalized with bioactive compounds from Cornus mas L. (AuNPsCM) in an experimental model of a high-fat diet (HFD), and we assessed their effects on aorta wall but also in the serum, as compared to Cornus mas (CM) administration. Sprague Dawley female rats were fed for 9 months with an HFD. During the last month of the experiment, we randomly allocated the animals into three groups that received, by oral gavage: saline solution, CM solution (0.158 mg/mL polyphenols) or AuNPsCM solution (260 µg Au/kg/day), while a Control group received a standard diet and saline solution. At the end of the experiment, we performed an ultrasonography of the aorta and left ventricle and a histology and transmission electron microscopy of the aorta walls; we investigated the oxidative stress and inflammation in aorta homogenates and in serum and, in addition, the lipid profile. AuNPsCM presented better effects in comparison with the natural extract (CM) on lipid peroxidation (p < 0.01) and TNF-alpha (p < 0.001) in aorta homogenates. In serum, both CM and AuNPsCM decreased the triglycerides (p < 0.001) and C-reactive protein (CM, p < 0.01; AuNPsCM, p < 0.001) and increased the antioxidant protection (p < 0.001), in comparison with the HFD group. In intima, AuNPsCM produced ultrastructural lesions, with the disorganization of intima and subendothelial connective layer, whereas CM administration preserved the intima normal aspect, but with a thinned subendothelial connective layer. AuNPsCM oral administration presented certain antioxidant, anti-inflammatory and hypolipidemic effects in an experimental model of HFD, but with a negative impact on the ultrastructure of aorta walls, highlighted by the intima disorganization.

Neuronal apoptosis can be prevented by the combined therapy with melatonin and hypothermia in a neonatal rat model of hypoxic-ischemic encephalopathy.

INTRODUCTION: Birth hypoxia is a leading cause of perinatal mortality and neurological morbidity, resulting in central nervous system injury. Cerebral hypoxia and ischemia can produce a severe brain damage following a typical pattern, defined by selective vulnerability of the brain regions. The neonates are most prone to hypoxic-ischemic injuries due to the lack of efficient antioxidant defense. Neonatal hypoxia-ischemia (HI) in a 7-day-old rat HI model can produce cell death by apoptotic or necrotic mechanisms. The degree of apoptotic or necrotic mechanisms responsible for cell death in neonatal hypoxia-ischemia are not very clear as yet. The form of neuronal death may also depend on the severity of ischemic injury. Necrosis predominates in more severe cases, whereas apoptosis occurs in areas with milder ischemic injury. A human study demonstrated apoptotic and necrotic forms of cell death after hypoxic injury, whereas in some brains from stillbirths, only apoptotic figures were observed. The expression of activated caspase-3 reflects the role of apoptosis in neonatal hypoxic ischemic brain injury. OBJECTIVES: The aim of this study was to evaluate the possible neuroprotective effect of melatonin and hypothermia in hypoxic-ischemic encephalopathy in newborn rats. Local damages induced by hypoxia and ischemia were assessed by evaluating the changes in terms of histology and apoptosis. METHODS: The experiment was conducted on 20 newborn Wistar rats premedicated for seven days with melatonin in a dose of 20 mg/kg/day. On the 7th postnatal day (P7), the newborn rats were exposed to ischemia (by clamping the right carotid artery) and hypobaric hypoxia (8% O2 for 90 minutes) and some groups to hypothermia. RESULTS: In this experimental model of neonatal encephalopathy, melatonin, in a dose of 20 mg/kg/day has neuroprotective effect by reducing the number of cells expressing apoptosis in Cornu Ammonis (CA) (Ammon's Horn) CA1, CA2, CA3 and dentate gyrus of the hippocampus when combined with hypothermia. CONCLUSION: The results of this study prove that melatonin is protective in ischemic-hypoxic brain injuries, but the protection is conditioned in most of the brain regions (excepting cerebral cortex) by conjugation with post-injury hypothermia treatment.

Chitosan Functionalized Magnetic Nanoparticles to Provide Neural Regeneration and Recovery after Experimental Model Induced Peripheral Nerve Injury.

(1) Background: Peripheral nerve injuries have a great impact on a patient's quality of life and a generally poor outcome regarding functional recovery. Lately, studies have focused on different types of nanoparticles and various natural substances for the treatment of peripheral nerve injuries. This is the case of chitosan, a natural compound from the crustaceans' exoskeleton. The present study proposes to combine chitosan benefic properties to the nanoparticles' ability to transport different substances to specific locations and evaluate the effects of magnetic nanoparticles functionalized with chitosan (CMNPs) on peripheral nerve injuries' rehabilitation by using an in vivo experimental model. (2) Methods: CMNPs treatment was administrated daily, orally, for 21 days to rats subjected to right sciatic nerve lesion and compared to the control group (no treatment) by analyzing the sciatic functional index, pain level, body weight, serum nerve growth factor levels and histology, TEM and EDX analysis at different times during the study. (3) Results: Animals treated with CMNPs had a statistically significant functional outcome compared to the control group regarding: sciatic functional index, pain-like behavior, total body weight, which were confirmed by the histological and TEM images. (4) Conclusions: The results of the study suggest that CMNPs appear to be a promising treatment method for peripheral nerve injuries.

Mind-Body Interventions as Alternative and Complementary Therapies for Psoriasis: A Systematic Review of the English Literature.

OBJECTIVE: Conventional therapeutic methods for psoriasis include topical and systemic drugs, phototherapy, and biologic agents. Despite the fact that these treatment methods, and especially biologic agents, are met with a considerable reduction in disease activity, they can sometimes be costly and are nonetheless accompanied by high risks of adverse events, ranging from mild to debilitating. Therefore, complementary and alternative medicine (CAM), especially mind-and-body interventions, such as acupuncture, psychotherapy, climatotherapy, and cupping may provide a cheaper and potentially beneficial outcome for these patients. METHODS: We performed a systematic review of articles pertaining to acupuncture, cupping, psychotherapy and meditation, as well climatotherapy and balneotherapy in the management of psoriasis, by using the PubMED, Medline and Google Academic research databases and reference cross-checking. RESULTS: 12 articles on acupuncture, 9 on dry or wet cupping, 27 concerning meditation, hypnosis or psychotherapy, and 34 regarding climate therapy or balneotherapy were found. DISCUSSION AND CONCLUSIONS: Currently, there is a lack of evidence in the English literature to support acupuncture as an effective alternative therapy for psoriasis, whereas cupping has been described in the majority of instances to result in Koebner phenomenon and clinical worsening. Stress management therapies such as psychotherapy, hypnosis, and meditation have shown promising results as complementary treatment methods. Climatotherapy and balneotherapy have already been proven as effective means of achieving clinical improvement in psoriasis. Further research is still needed to verify the usefulness of the lesser studied treatment methods.

An updated guide in the management of psoriasis for every practitioner.

BACKGROUND: Psoriasis is one of the most common chronic cutaneous skin disorders, having genetic and immunological components. It is currently unknown what exactly triggers it, or how far reaching are the etiological factors, although great strides have been made in uncovering the pathophysiological cascade. Presently, there is a wide diversity of treatment methods for psoriasis, yet not all are applicable for each patient. Selection of both drug and dosage depends on both the knowledge and experience of the treating dermatologist and also on the specific characteristics of each patient. Therefore, the treating physicians should be made aware of the management possibilities, their advantages and their side effects. METHODS: We have performed a non-systematic literature review on the current treatment methods for psoriasis. We have included the studies, articles, and prescription information that provided the most relevant information regarding each therapeutic agent. Afterward, we divided the treatment methods according to delivery and illustrated the management protocols for adult, paediatric, and pregnant patients. DISCUSSION AND CONCLUSIONS: Current therapies are divided into topical drugs, phototherapy, systemic and biological agents. Topical therapies and phototherapy are generally the first and second line of management respectively, being typically effective in treating mild to moderate forms of psoriasis. On the other hand, the chronic moderate to severe forms usually benefit from systemic drugs, whereas biologic agents are reserved for severe or unremitting cases, especially those suffering from psoriatic arthritis. Also of importance is the understanding of the pathophysiological mechanisms in psoriasis and how the selected drugs interfere in the pathological cascade. Furthermore, physicians should be able to recommend the appropriate therapy not only for adults but also for paediatric and pregnant patients as well. In the following manuscript, we present an updated version of these management options, alongside their indications, posology and most common side effects, a guide that may be useful for every practitioner in this field.

The impact of silver nanoparticles phytosynthesized with Viburnum opulus L. extract on the ultrastrastructure and cell death in the testis of offspring rats.

AIM: To investigate the effects of prenatal exposure to AgNPs obtained by green synthesis with Viburnum opulus L. extract on the testis in male offspring rats. MATERIAL AND METHODS: Two different doses of AgNPs (0.8 and 1.5 mg/kg b.w.) and vehicle (PBS) were administered to Wistar female rats on days 3-14 of gestation. At 6 weeks after birth, the ultrastructural changes in correlation with the amount of silver as well as the parameters of oxidative stress, inflammation and cell death mechanisms in the testis of male offspring were evaluated. RESULTS: AgNPs administered during pregnancy crossed the placental and testicular barriers and induced oxidative stress, DNA damage and autophagy as mechanism of cell toxicity. The markers of inflammation and apoptosis decreased after AgNPs exposure while the NFkB activation increased. TEM examination revealed important ultrastructural changes of Sertoli cells, numerous vacuoles and cytoplasmic changes suggestive of the cell's evolution towards necrosis. CONCLUSION: Phytoreduced silver nanoparticles with polyphenols from Viburnum opulus L. fruit extract, administered during the embryological development of the male gonad, have testicular toxic effects in offspring even at 6 weeks after birth.

Quercetin and curcumin effects in experimental pleural inflammation.

BACKGROUND: The inflammatory mechanisms occur with the highest prevalence in pulmonary pathology in addition to oxidative stress and activation of intracellular signaling pathways. The oxidative stress represents the imbalance between pro-oxidants and antioxidants which can lead to the activation of the oxidative mechanisms with noxious potential to the body. Therefore, finding a therapy that would counteract the injurious effects of free radicals and inflammation is highly attractive. Quercetin is the most active flavonoid, with important anti-inflammatory and antioxidant effects, while curcumin has antioxidant effects that are similar to the standard antioxidants and exerts direct anti-inflammatory activity. AIMS: The aim of this study is to evaluate the antioxidant effects of quercetin and curcumin on an experimental model, pleural inflammation induced by carrageenan. METHODS: Eight groups of adult male rats were used: Ia and Ib - control groups, IIa and IIb - with carrageenan administration, IIIa and IIIb - received curcumin and carrageenan, IVa and IVb - quercetin and carrageenan administration. Blood and lung samples were taken at 4 hours (Ia, IIa, IIIa, IVa groups) and at 24 hours (Ib, IIb, IIIb, IVb groups) after carrageenan injection. RESULTS: At 4 and at 24 hours, curcumin and quercetin have shown protective systemic effects, decreasing significantly the oxidative stress (malondialdehyde level) and stimulating significantly the antioxidant protection (ceruloplasmin and glutathione levels) compared to the group that received only carrageenan. In the lungs, at 4 hours, the redox misbalance was significantly reduced only in animals that were treated with quercetin, modifications that were not observed at 24 hours. CONCLUSIONS: In serum, curcumin presented higher antioxidant effects, compared to quercetin. In lungs, quercetin administration showed superior beneficial effects, but only temporarily.