An intravitreal biodegradable sustained release naproxen and 5-fluorouracil system for the treatment of experimental post-traumatic proliferative vitreoretinopathy

BACKGROUND/AIMS: To determine the potential of an intravitreal sustained release naproxen and 5-fluorouracil (NA/5-FU) codrug for the treatment of experimental proliferative vitreoretinopathy (PVR) in a model for trauma associated tractional retinal detachment (TRD). METHODS: Sustained release pellets were prepared by covalently linking naproxen to 5-fluorouracil. Drug release was tested in vitro and toxic effects were evaluated by electroretinography and light microscopy. Traumatic PVR was induced in pigmented rabbits by performing a scleral laceration, followed by repair and intravitreal injection of 0.4 ml of autologous blood. Thirty six eyes were treated with a sustained release implant containing 1.5 mg NA/5-FU as a codrug and 36 control eyes were submitted to surgery alone. Eyes were evaluated for TRD by serial indirect ophthalmoscope examination at different time points followed by postmortem fundus evaluation of the enucleated eye RESULTS: The NA/5-FU pellets were found to provide linear release of 5-FU and naproxen over the 30 day duration of the in vitro release test. Both the severity of PVR grade and the percentage of eyes with moderate or worse tractional detachment were significantly lower in eyes treated with the codrug pellet. There were no drug related toxic effects evident on histopathological or electroretinograph examination of eyes containing the NA/5-FU pellet. CONCLUSIONS: The results suggest that this NA/5-FU codrug device effectively inhibits the progression of PVR in a rabbit trauma model that closely resembles PVR in humans. Additional studies to add knowledge to these initial findings and to clarify the potential of the codrug device for the treatment of human PVR are warranted.     

Vitamin D Treatment Prevents Uremia-Induced Reductions in Aortic microRNA-145 Attenuating Osteogenic Differentiation despite Hyperphosphatemia

In chronic kidney disease, systemic inflammation and high serum phosphate (P) promote the de-differentiation of vascular smooth muscle cells (VSMC) to osteoblast-like cells, increasing the propensity for medial calcification and cardiovascular mortality. Vascular microRNA-145 (miR-145) content is essential to maintain VSMC contractile phenotype. Because vitamin D induces aortic miR-145, uremia and high serum P reduce it and miR-145 directly targets osteogenic osterix in osteoblasts, this study evaluated a potential causal link between vascular miR-145 reductions and osterix-driven osteogenic differentiation and its counter-regulation by vitamin D. Studies in aortic rings from normal rats and in the rat aortic VSMC line A7r5 exposed to calcifying conditions corroborated that miR-145 reductions were associated with decreases in contractile markers and increases in osteogenic differentiation and calcium (Ca) deposition. Furthermore, miR-145 silencing enhanced Ca deposition in A7r5 cells exposed to calcifying conditions, while miR-145 overexpression attenuated it, partly through increasing α-actin levels and reducing osterix-driven osteogenic differentiation. In mice, 14 weeks after the induction of renal mass reduction, both aortic miR-145 and α-actin mRNA decreased by 80% without significant elevations in osterix or Ca deposition. Vitamin D treatment from week 8 to 14 fully prevented the reductions in aortic miR-145 and attenuated by 50% the decreases in α-actin, despite uremia-induced hyperphosphatemia. In conclusion, vitamin D was able to prevent the reductions in aortic miR-145 and α-actin content induced by uremia, reducing the alterations in vascular contractility and osteogenic differentiation despite hyperphosphatemia.     

Ablación de taquicardia ventricular asistida con ECMO. Primera experiencia en nuestra institución

Catheter ablation is useful for reducing drug refractory ventricular tachycardia (VT) episodes and can be life-saving when VT is incessant or arrhythmic storm. Left ventricular hemodynamic support may be required in patients with VT and hemodynamic instability. Extracorporeal membrane oxygenation (ECMO) support is an alternative to achieve ventricular tachycardia mapping and ablation over long periods of time. We present a case of successful catheter ablation of substrate in a patient with ischemic heart disease and ventricular tachycardia with hemodynamic instability performed using venous- arterial ECMO support. There were not episodes of ventricular tachycardia after 2 years of follow-up.     

Ternary Blends for Self-Compacting Mortars Production Composed by Electric Arc Furnace Dust and Other Industrial by-Products

This study is framed within the circular economy model through the valorisation of industrial by-products. This research shows the results of producing self-compacting mortars (SCMs) with electric arc furnace dust (EAFD) and other industrial by-products such as fly ash, conforming (FA) or not conforming (NcFA), from coal-fired power plants, or recovery filler (RF) from hot-mix asphalt plants. Three batches of SCMs, each with one industrial-by product (FA, NcFA, or RF), and three levels of EAFD ratio incorporation (0%, 10%, 20%), were tested. An extra batch with a greater amount of FA was manufactured. When the incorporation ratio of EAFD rose, the mechanical strength decreased, due to the presence of a calcium zinc hydroxide dihydrate phase; nevertheless, this decrease diminished over time. All SCM mixes, except the 40C 40FA 20 EAFD mix, were above 20 MPa at 28 days. All mixes named 70C and 40C reached 40 and 30 MPa, respectively, at 90 days. Mixes with EAFD showed less capillarity and no difference in water absorption by immersion with respect to mixes without EAFD after 91 days. The SCMs designed proved to be stable in terms of leaching of the heavy metals contained in EAFD, where all the hardened SCMs were classified as inert.     

Spontaneous uterine rupture in a patient with polyhydramnios as only risk factor. Case report, literature review and institutional experience

The uterine rupture is a catastrophic obstetric complication. The main risk factor is an antecedent of uterine surgery, usually caesarean. It is reported the case of a 39-years-old patient with 37 week-pregnancy and polyhydramnios, without surgical antecedents, whose was not in labor and developed complete rupture of the lateral face of the uterus, which was spontaneous, without previous uterine scar and with a unusual outcome.     

Effect of raloxifene on the vaginal epithelium of postmenopausal women

OBJECTIVE: The objective was to analyze the effect of raloxifene on the vaginal epithelium of postmenopausal women. STUDY DESIGN: In this non-randomized clinical trial, 80 women (mean age = 60.6 years) were prospectively studied. Forty patients received 60 mg/day of raloxifene (RG), and 40 women constituted a non-treated control group (CG), paired by age and time since menopause. The treated group consisted of patients with osteoporosis of the lumbar spine. Those with a diagnosis of infection in the lower genital tract and using hormone therapy (HT) up to 6 months prior to the study were excluded. Vaginal smears were collected at baseline and after 6 months of intervention. The vaginal maturation value (VMV) was determined, and counts of superficial, intermediate and parabasal cells were performed. Smears were analyzed by only one cytopathologist who was blinded to patient data. The t-test, Wilcoxon test, and Chi-Squared test were used in the statistical analysis. RESULTS: The study groups were homogeneous regarding age, time since menopause, parity, HT use, smoking, and body mass index. No statistically significant differences were observed in VMV median values (RG, 39.7 and 35.7; CG, 50.0 and 50.0, respectively) or in the percentage of superficial, intermediate and parabasal cells between the groups at baseline and after 6 months (p>0.05). There was no significant correlation between VMV and age, time since menopause, previous HT use, or body mass index, in either of the groups. CONCLUSION: Treatment with raloxifene for 6 months has no effect on the maturation of the vaginal epithelium in postmenopausal women with osteoporosis.     

Effectiveness of fetal fibronectin testing compared with digital cervical assessment of women with preterm contractions

The purpose of this study is to determine the effectiveness of fetal fibronectin (FFN) compared to assessment of cervical dilation (CD) in clinical management of women with symptomatic preterm labor (PTL). Pregnant women presenting to Thomas Jefferson University Hospital between May 1, 2001 and November 30, 2002 with symptomatic PTL underwent FFN sampling and had a complete clinical evaluation including a pelvic bimanual examination. Inclusion criteria were singleton pregnancy, gestational age (GA) between 24 (0) and 33 (6) weeks, CD < 3 cm, and intact amniotic membranes. FFN samples were sent out and results were available within 4-12 hours. Clinical management including tocolysis, antenatal steroids, and hospitalization was determined based on digital CD assessment and FFN status. A dilated cervix was defined as CD > 1 cm. Ninety-three patients were included. Spontaneous preterm delivery (SPTD) at < 37 weeks occurred in 20 of 93 (21.5%) patients. Medical therapy use was significantly higher in patients with dilated cervix than in those with a closed cervix (all P values < 0.05). Tocolysis and steroid use in FFN-negative patients and FFN-positive patients were not significantly different. Furthermore, tocolytic use was higher in FFN-negative patients than in women with positive FFN (50% versus 42.1%; P = 0.53). Use of antenatal steroids was similar in patients with CD >/= 1 cm and a positive FFN (54.5% versus 47.4%; P = 0.92). Compared with FFN-negative patients, women with closed cervix were less likely to undergo interventions. In symptomatic PTL patients, CD determined clinical management more than FFN status. Overall, the use of FFN was not effective in decreasing "unnecessary" clinical interventions.