Bioinspired silk fibroin nano-delivery systems protect against 5-FU induced gastrointestinal mucositis in a mouse model and display antitumor effects on HT-29 colorectal cancer cells in vitro.

Colorectal cancer (CRC), is the second cause of cancer-related deaths worldwide is one of the most prevalent types of cancers. Conventional treatment continues to rely on surgery, chemotherapy, and radiotherapy, but for advanced cases, adjuvant chemotherapy remains the main approach for improving surgical outcomes and lower the disease recurrence probability. Chemotherapy-induced gastrointestinal (GI) toxicity is the main dose-limiting factor for many chemotherapeutic regimens, including 5-FU, and one of the biggest oncological challenges. Up to 40% of the patients receiving 5-FU get mucositis, 10-15% of which develop severe symptoms. In this context, our study aimed to develop a bioinspired nanosized drug delivery system as a strategy to reduce 5-FU associated side effects, such as GI mucositis. To this end, SF-based nanoparticles were prepared and characterized in terms of size and morphology, as well as in terms of in vitro antitumoral activity on a biomimetic colorectal cancer model by investigation of apoptosis, DNA fragmentation, and release of reactive oxygen species. Additionally, the capacity of the SF-based nanocarriers to offer intestinal protection against 5-FU-induced GI mucositis was evaluated in vivo using a mouse model that mimics the chemotherapy-associated gut mucositis occurring in colorectal cancer. Our studies show that silk fibroin nanoparticles efficiently deliver 5-FU to tumor cells in vitro while protecting against drug-induced GI mucositis in a mouse model.

CARDIOVASCULAR RISK ASSESSMENT IN THE ADULT (AGED 40-79 YEARS) ROMANIAN POPULATION.

Atherosclerotic Cardiovascular Diseases are the leading cause of death worldwide. AIM: To estimate the prevalence of cardiovascular risk (CVR) categories in the adult population (aged 40-79 years) of Romania. DESIGN: The present study was part of the epidemiological, cross-sectional PREDATORR study (PREvalence of DiAbeTes mellitus, prediabetes, overweight, Obesity, dyslipidemia, hyperuricemia and chronic kidney disease in Romania). SUBJECTS AND METHODS: Exclusion criteria: age <40/or>79 years old and diagnosis of ischemic vascular disease. The CVR was evaluated using charts developed by the World Health Organization/ International Society of Hypertension (WHO/ISH) available for Europe B (epidemiological sub-region where Romania was included). The CVR was divided into 5 categories: <10%, 10-20%, 20-30%, 30-40%, > 40%. RESULTS: A total of 1631 subjects (57.0±10.7 years, 45.1% males) were included in the present study.The age and sex-adjusted prevalence of CVR >40% was 2.9% (95%CI 2.8-3.1%), CVR 30-40% was 1.85% (95%CI 1.8-1.9%), CVR 20-30% was 5.8% (95%CI 5.6-6.0%) and 13.0% (95%CI 12.8-13.3%) of the adult Romanian population has a 10-20% CVR, these CVR categories being more frequent in male and older age. Diabetes, overweight/obesity and smoking were associated with high CVR categories. CONCLUSION: Romania is one of the countries with high CVR, requiring CVD prevention measures.

Acute cardiotoxicity induced by doxorubicin in right ventricle is associated with increase of oxidative stress and apoptosis in rats.

Doxorubicin (DOX) is one of the most effective chemotherapeutic agents, but its efficiency is seriously limited by the risk of developing cardiomyopathy. The most recognized cardiotoxic effect is left ventricular (LF) dysfunction, but MRI and echocardiography data demonstrated significant right ventricle (RV) function impairment. In order to clarify this aspect, the present study investigated the potential of DOX to induce acute RV cardiotoxicity at the same time as LV impairment. Rats were intraperitoneally (i.p.) injected with a single dose of 15 mg/kg DOX. DOX-treated rats were characterized by decreased body and heart weights, elevated levels of creatine kinase (CK-MB) and lactate dehydrogenase (LDH) activities compared to controls. Biochemical analyses on RV tissue revealed that the level of malondialdehyde (MDA) was significant increased (p<0.05) and activities of catalase (CAT), glutathione reductase (GR), glutathione peroxidase (GPX) antioxidant enzymes were decreased by 13%, 27% and 18%, respectively, compared to control. Histopathogical and electron microscopic studies revealed DOX-induced damage in both ventricles and an increase of interstitial collagen fibers compared to controls (p<0.001), whereas immunohistochemical analysis showed weak and irregular desmin expression. Furthermore, mitochondrion-induced apoptotic pathways were also activated in both ventricles, as reflected by the up-regulation of Bax/Bcl-2 mRNA expression ratio (p<0.001) and increase of Bax and caspase-3 protein expression, as well as by the significant elevation of TUNEL positive nuclei, compared to controls (p<0.001). The results showed that DOX exerted RV toxic effects at the same time as those reported in the LV, which might be mediated through the mitochondrial-dependent apoptosis.

Graphene oxide vs. reduced graphene oxide as carbon support in porphyrin peroxidase biomimetic nanomaterials.

The paper describes the preparation of supramolecular assemblies of tetrapyridylporphyrin (TPyP) and its metallic complexes with graphene oxide (GO) and thermally reduced graphene oxide (TRGO). The two carbon supports are introducing different characteristics in the absorption spectra of the investigated nanocomposites. Raman spectroscopy shows that the absorption of iron-tetrapyridylporphyrin is more efficient on GO than TRGO, suggesting that oxygen functionalities are involved in the non-covalent interaction between the iron-porphyrin and graphene. The biomimetic peroxidase activity is investigated and the two iron-containing composites exhibit a better catalytic activity than each component of the assembly, and their cobalt and manganese homologues, respectively. The main advantages of this work include the demonstration of graphene oxide as a very good support for graphene-based nanomaterials with peroxidase-like activity (K(M)=0.292 mM), the catalytic activity being observed even with very small amounts of porphyrins (the TPyP:graphene ratio=1:50). Its potential application in the detection of lipophilic antioxidants (vitamin E can be measured in the 10(-5)-10(-4) M range) is also shown.

One step forward in health promotion.

Thalassemias are inherited blood disorders. In 2011, there was no clear situation regarding the number of thalassemia or other hemoglobinopathy patients in Romania. The luck of information has led to an increased number of patients registered by Fundeni Hospital, Bucharest in the last years. The main goal of this article is to underline the importance of implementing a screening program in Romania for thalassemia and other hemoglobinopathies, parallel with an awareness program. The importance of this objective is strongly supported by the following example: in Sardinia, thalassemia major was present in one out of 250 births, and has declined to one out of 4000 births after they implemented the screening program. The article is written by Monica Rosu, a participant to the World Wide Opportunities for Woman course, held in Canada, in 1999 and states one of the first results of thalassemia awareness in Romania with a positive impact on the patient's life, registering the following results: 2000: A website in Romanian language regarding thalassemias and addressed to patients was created. 2005: The Association of People with thalassemia major was founded and become member of Thalassemia International Federation. 2011: Thalassemia major patients from Romania have access to free treatment and the latest medical oral chelator, Exjade. The association participated in various meetings addressed to patients and doctors as well, created their own website, held workshops, fought together for an improved quality of life for themselves, for healthy people (possible thalassemia carriers) and for all Romanian children.

[Right atrial thrombosis with acute abdominal onset]. / Tromboza de atriu drept cu debut de abdomen acut.

Intracardiac masses are detected more frequently due to the availability of echocardiography. Right atrial thrombosis is rare comparatively with that of the left atrium. The clinical presentation of the patient with right atrial thrombosis is linked with a misleading association between cardiovascular signs and digestive signs (acute abdominal pain, vomiting and marmorated skin of flanks). Initial clinical suspicions of acute pancreatitis, entero-mesenteric infarction and complicated gastro-duodenal ulcer were invalidated by imagistic investigations -- echocardiography and CT. The massive thrombus located in the right atrium, prolapsing during diastole through the tricuspid valve, was associated with the increase in plasmatic D-dimers and new ECG modifications type right bundle block (hemodynamic straining of the right ventricle). The evolution was favorable, after heparin-therapy by infusing pump, with relief of cardiovascular and digestive symptoms after the first 6 hours; after 36 h from the beginning of the treatment the thrombus was lysed. Sudden death likelihood through complete obstruction of the tricuspid ostium was prevented due to the early diagnosis offered by imagistic methods.

Effects of 3-month treatment with the antioxidant alpha-lipoic acid in diabetic peripheral neuropathy.

Alpha lipoic acid is a natural antioxidant that has been suggested to improve symptoms of diabetic neuropathy. To assess these potential benefits, a cohort of 26 type 2 diabetic patients with symptomatic peripheral neuropathy (stage 2) received a daily dose of 600 mg alpha-lipoic acid, and were followed for a 3 month-period. No dropout was noted. At the end of the follow-up period, in 20 subjects (76.9%) there was a 1-stage regression of somatic neuropathy (from symptomatic to asymptomatic neuropathy, and in 5 patients (19.2%) no signs of neuropathy were found. The nerve conduction velocity of motor fibers improved from 36.8 (95% Confidence Interval CI = 30.9-42.7) meters/second to 41.3 (95% CI = 39.5-43.0) meters/second (p = 0.049, paired t test). Mean blood glucose measured was significantly lower at 3 months than at baseline [197.9 (95% CI = 170.1-225.7) versus 162.2 (95% CI = 146.1-178.2 mg/dl, p = 0.02, paired t test)]. In a multiple linear regression model with age. sex, body mass index, diabetes duration and the difference between blood glucose values at 3 months and at baseline as explanatory variables, the increment in nerve conduction velocity was not accounted for by the improved glycemic control. Women, thinner and younger patients tended to benefit more from the treatment in terms of nervous conduction velocity improvement. In conclusion, alpha-lipoic acid seems to be efficient and safe in the treatment of diabetic peripheral neuropathy, improving both clinical manifestations and nerve conduction velocity. Placebo controlled clinical trials are needed to further define the role of this new medication in the treatment of diabetic neuropathies.

The value of serial postoperative radiographs of total knee arthroplasties.

In a prospective study of 35 cemented press fit condylar knees, we studied the prevalence of radiolucent lines 1 mm wide or wider using two methods of detection: conventional (plain) and fluoroscopically-guided radiographs. All films were evaluated in accordance with the Knee Society Total Knee Arthroplasty Roentgenographic Evaluation and Scoring System. A total of 12 radiolucencies were detected in nine knees (26% of all knees) using conventional radiographs versus 25 radiolucencies in 13 knees (37% of all knees) using fluoroscopically-guided radiographs. This was a statistically significant difference and suggests that the true prevalence of periprosthetic radiolucencies will be underestimated if conventional radiographs are used to evaluate the bone-prosthesis interfaces and questions the value of routine postoperative plain film radiographs to evaluate the results of knee arthroplasty.