The molecular mosaic of the premalignant cutaneous lesions.

In the last three decades, the premalignant cutaneous lesions have represented a milestone for the clinicians and the anatomopathologists given the increased risk of malignant transformation not only in the old but also in the young population. Recent research indicates the fact that, though multiple progresses were recorded in the diagnosis and treatment of the cutaneous squamocellular carcinomas, developed in more than 85% of the cases in premalignant lesions, however the prognosis and survival up to five years did not register significant improvements. For the achievement of the diagnosis with certainty, the histopathological examination, considered until recently the "golden standard", principally based on the TNM criterion, has an increased percentage of subjectivity and it is relatively unsure, being known the fact that two apparently identical tumors answer differently to the same therapy. The variability of the morphological aspects from simple dysplasia to in situ carcinomas and the cancers themselves impose the identification of some cellular and molecular markers typical to the premalignant and malignant cutaneous lesions. In this respect, the knowledge and characterization of the molecular mosaic allow the establishment of some clear criterion for an early diagnosis, corresponding monitoring and adequate treatment.

The beneficial effects on blood pressure, dyslipidemia and oxidative stress of Sambucus nigra extract associated with renin inhibitors.

CONTEXT: The health effects of Sambucus nigra L. (Caprifoliaceae) could be due to polyphenols whose modes of action differ from the traditional one proposed for exogenous antioxidants. OBJECTIVE: The study emphasizes the effects of the association between the renin inhibitor and the polyphenolic extract on biochemical parameters and systolic (TAS) and diastolic (TAD) blood pressure within an L NAME-induced experimental model of arterial hypertension (AHT). MATERIALS AND METHODS: The polyphenols are extracted with ethanol from isolated and purified vegetable material represented by the mature fruit of the S. nigra with a dosage of 0.046 g/kg body weight (PS), every 2 days, for 8 weeks. The dose represents 1/20 of LD50. The Wistar white rat blood pressure values were recorded using a CODA™ system, which uses a non-invasive blood pressure measuring method. RESULTS AND DISCUSSION: The total antioxidant capacity levels were significantly decreased (p < 0.001) in AHT group as compared to the rats in the AHT + PS group. A combination of a renin inhibitor (Aliskiren) and polyphenolic extract generated a superior antioxidant effect compared to administering the two separately. Both TAS and TAD in rats with drug-induced hypertension were reduced by polyphenolic extract. The homogeneous values of TAS record a significant decrease (p < 0.001) of the average values in AHT + PS group or AHT + Aliskiren group. CONCLUSION: The combination of two different classes of substances, namely, renin inhibitors and natural polyphenol extracts, reduces arterial pressure and also might reduce the side effects of the major classes of antihypertensive agents and improve the quality of live.

Effects of Sambucus nigra and Aronia melanocarpa extracts on immune system disorders within diabetes mellitus.

CONTEXT: The fruits of Aronia melanocarpa Elliot (Rosaceae), (black chokeberry), and Sambucus nigra L. (Caprifoliaceae), elderberries are rich in anthocyanins. Many studies have reported that anthocyanins are beneficial in diabetes due to their capacity to stimulate insulin secretion and reduce oxidative stress. OBJECTIVE: The purpose of this study is to prove the biologically active properties of polyphenols extracted from S. nigra and A. melanocarpa fruit. The study also details the influence of plant polyphenols on immune system imbalances within diabetes mellitus. MATERIALS AND METHODS: Polyphenolic extract was administered to Wistar rats 0.040 g/kg body every 2 d for 16 weeks. The absorbencies of all the solutions were determined using a V-550 Able Jasco UV-VIS spectrophotometer. The immunomodulatory capacity of vegetal extracts was assessed by studying cytokines TNF-α and IFN-γ through the ELISA method and fibrinogen values. RESULTS AND DISCUSSION: At 48 h, the anti-inflammatory effects of S. nigra and A. melanocarpa substances have been revealed by an increase of the TNF-α and IFN-γ levels in the diabetic group protected by these extracts. Seventy-two hours post-administration of both substances in the diabetic groups, the TNF-α level returns to the values read 24 h after substance administration. The vegetal extracts limit the production of fibrinogen in the diabetic rats under polyphenolic protection, the values being highly significant compared with the diabetic group. CONCLUSIONS: Natural polyphenols extracted from S. nigra and A. melanocarpa modulate specific and non-specific immune defenses in insulin-deficiency diabetes and reduce the inflammatory status and self-sustained pancreatic insulitis.

Modulation of neuropathic pain in experimental diabetes mellitus

The main objective of the current article is to investigate the diabetic polyneuropathy which represents a major preoccupation within the context of high incidence of diabetes mellitus (DM) and its complications. Moreover, neuropathy may develop despite intensive hyperglycaemic control. The effect of Zn and black grape seed polyphenols (BGSP) in streptozotocin diabetic rats was studied. Zn and BGSP were administered by gavage, daily, for 16 weeks to Wistar rats that have been rendered diabetic by a single i.v. injection of streptozotocin (55 mg/kg body weight). Dysalgesia was investigated under the conditions of nociceptive stimulation through the following tests: the thermoalgesic mechanism through the tail-flick test, the hot plate test and the plantar test, and the mechanoalgesic mechanism through the algesimetric test. Thermal hyperalgesia detected in the diabetic group is significantly reduced (p < 0.001) through the administration of polyphenols, or even better, of Zn. Diabetes-associated mechanical hyperalgesia decreased significantly (p < 0.001) probably through the inhibition of the NMDA receptors. Administration of Zn or BGSP to the diabetic group improves glycosylated haemoglobin (HbA1c) values but does not bring them to normal. The present data suggest a favourable effect of Zn and BGSP in inhibiting diabetic complications by several mechanisms

Modulation of neuropathic pain in experimental diabetes mellitus.

The main objective of the current article is to investigate the diabetic polyneuropathy which represents a major preoccupation within the context of high incidence of diabetes mellitus (DM) and its complications. Moreover, neuropathy may develop despite intensive hyperglycaemic control. The effect of Zn and black grape seed polyphenols (BGSP) in streptozotocin diabetic rats was studied. Zn and BGSP were administered by gavage, daily, for 16 weeks to Wistar rats that have been rendered diabetic by a single i.v. injection of streptozotocin (55 mg/kg body weight). Dysalgesia was investigated under the conditions of nociceptive stimulation through the following tests: the thermoalgesic mechanism through the tail-flick test, the hot plate test and the plantar test, and the mechanoalgesic mechanism through the algesimetric test. Thermal hyperalgesia detected in the diabetic group is significantly reduced (p < 0.001) through the administration of polyphenols, or even better, of Zn. Diabetes-associated mechanical hyperalgesia decreased significantly (p < 0.001) probably through the inhibition of the NMDA receptors. Administration of Zn or BGSP to the diabetic group improves glycosylated haemoglobin (HbA1c) values but does not bring them to normal. The present data suggest a favourable effect of Zn and BGSP in inhibiting diabetic complications by several mechanisms.

The cytotoxic effect of magainin II on the MDA-MB-231 and M14K tumour cell lines.

Many studies have highlighted the tumoricidal properties of some natural peptides known to have antimicrobial virtues. Also, the increasingly higher resistance to conventional antibiotics has become a global public health issue, and the need for new antibiotics has stimulated interest in finding and synthesizing new antimicrobial peptides, which may also be used as chemotherapeutic agents. Relying on the literature, the purpose of our in vitro research was to assess the tumoricidal potential of magainin II on a series of tumour cell lines, namely, MDA-MB-231 (breast adenocarcinoma) and M14K (human mesothelioma). The experimental results of our study revealed that the cytotoxic effects of magainin II depend on its concentration. Its efficiency is significant at 120 µM concentrations, and, although it is much lower, it persists even at 60 µM concentrations. The effects were insignificant at 30 µM concentrations. In our experimental research, the tumoricidal effect of magainin II was not significantly dependent on the type of tumour cell line used.

The involvement of a polyphenol-rich extract of black chokeberry in oxidative stress on experimental arterial hypertension.

The aim of this study is to characterize the content of Aronia melanocarpa Elliott (black chokeberry) extract and also to estimate the influence of polyphenolic compounds contained in chokeberries on oxidative stress, on an L-NAME-induced experimental model of arterial hypertension. The rat blood pressure values were recorded using a CODA Noninvasive Blood Pressure System. HPLC/DAD coupled with ElectroSpray Ionization-Mass Spectrometry allowed identification of five phenolic compounds in berries ethanolic extract as follows: chlorogenic acid, kuromanin, rutin, hyperoside, and quercetin. The serous activity of glutathione-peroxidase (GSH-Px) has significantly lower values in the hypertensive (AHT) group as compared to the group protected by polyphenols (AHT + P). The total antioxidant capacity (TAC) values are lower in the AHT group and they are significantly higher in the AHT + P group. All the measured blood pressure components revealed a biostatistically significant blood pressure drop between the AHT group and the AHT + P group. The results reveal the normalization of the reduced glutathion (GSH) concentration as well as a considerable reduction in the malondialdehyde (MDA) serum concentration in the AHT + P group. Ethanolic extract of black chokeberry fruits not only has a potential value as a prophylactic agent but also may function as a nutritional supplement in the management of arterial hypertension.

Mechanism by Sambucus nigra Extract Improves Bone Mineral Density in Experimental Diabetes.

The effects of polyphenols extracted from Sambucus nigra fruit were studied in streptozotocin- (STZ-) induced hyperglycemic rats to evaluate its possible antioxidant, anti-inflammatory, antiglycosylation activity, and antiosteoporosis effects in diabetes. DEXA bone mineral density tests were performed in order to determine bone mineral density (BMD), bone mineral content (BMC), and fat (%Fat) in control and diabetic animals, before and after polyphenol delivery. As compared to the normoglycemic group, the rats treated with STZ (60 mg/kg body weight) revealed a significant malondialdehyde (MDA) increase, as an index of the lipid peroxidation level, by 69%, while the total antioxidant activity (TAS) dropped by 36%, with a consistently significant decrease (P < 0.05) in the activity of superoxide dismutase (SOD) and glutathione peroxidase (GPX). Also, the treatment of rats with STZ revealed a significant increase of IL-6, glycosylated haemoglobin (HbA(1c)), and osteopenia detected by DEXA bone mineral density tests. The recorded results highlight a significant improvement (P < 0.001) in the antioxidative capacity of the serum in diabetic rats treated with natural polyphenols, bringing back to normal the concentration of reduced glutathione (GSH), as well as an important decrease in the serum concentration of MDA, with improved osteoporosis status. Knowing the effects of polyphenols could lead to the use of the polyphenolic extract of Sambucus nigra as a dietary supplement in diabetic osteoporosis.