Mevinolin, an inhibitor of cholesterol synthesis, induces mRNA for low density lipoprotein receptor in livers of hamsters and rabbits.

Through the use of a quantitative solution hybridization assay with 32P-labeled cDNA probes, we found that mevinolin, an inhibitor of cholesterol synthesis, elevates the level of mRNA for the low density lipoprotein receptor in livers of hamsters and rabbits. In hamsters the maximal effect (3-fold increase) occurred at 0.1% mevinolin in the diet for 10 days. The same dose produced a maximal induction (10-fold) of mRNA levels for 3-hydroxy-3-methylglutaryl CoA reductase, the rate-limiting enzyme of cholesterol synthesis, and a maximal decrease (80%) in plasma cholesterol. The drug lowered the level of all cholesterol-carrying lipoproteins in plasma. In normal rabbits, mevinolin produced a 90% reduction in plasma low density lipoprotein-cholesterol levels, which was associated with a 2.5-fold increase in low density lipoprotein receptor mRNA levels. A similar induction of receptor mRNA occurred in livers of Watanabe-heritable hyperlipidemic rabbits, although the plasma cholesterol was not reduced to normal, presumably because the receptors produced by the mutant mRNA function poorly. These data are consistent with the hypothesis that mevinolin and other inhibitors of 3-hydroxy-3-methylglutaryl CoA reductase lower plasma cholesterol levels in part by stimulating production of mRNA for the low density lipoprotein receptor in liver.     

Hepatic,Renal and Inflammatory Biomarkers are Positively Associated with Blood Pressure Changes in Healthy Pregnant Women: A Prospective Cohort

This article evaluates the association of hepatic, renal, and inflammatory biomarkers with changes in systolic (SBP) and diastolic (DBP) blood pressure (BP) during healthy pregnancies.A prospective cohort study with 225 healthy pregnant women was conducted in Rio de Janeiro, Brazil. SBP and DBP were evaluated throughout pregnancy (5th–13th, 20th–26th, and 30th–36th gestational weeks) and were the outcomes. The following biomarkers were measured at the first trimester and analyzed according to tertiles of the sample distribution and were considered the main independent predictors: alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), uric acid (UA), creatinine (Cr), and C-reactive protein (CRP) concentrations. The statistical analysis included 3 stages of modeling with the longitudinal linear mixed-effects procedures: Model 1 was adjusted for gestational age and quadratic gestational age; Model 2 included interactions between the biomarkers and gestational age; and Model 3 was adjusted for self-reported skin color, education, parity, early-pregnancy body mass index (BMI) (under/normal <25; overweight/obese ≥25 kg/m²), smoking habit, and leisure-time physical activity. Additional models were performed for CRP and UA with the inclusion of interaction terms between the biomarkers and BMI.Women classified in the third tertile of the ALP (≥61.1 U/L; β_SBP = 3.474; 95% confidence interval [CI]: 0.955–5.992; β_DBP = 3.291; 95% CI: 1.098–5.485), ALT (≥14.3 U/L; β_SBP = 2.232; 95% CI: 0.221–4.242; β_DBP = 2.355; 95% CI: 0.721–3.989), and Cr values (≥48.6 μmol/L; β_DBP = 1.927; 95% CI: 0.347–3.508) presented higher BP levels during pregnancy compared to those in the first and second tertiles. Women in the highest tertile of the ALP concentration distribution presented a lower rate of change in SBP and DBP during pregnancy (interaction term with gestational age β_SBP = −0.004; 95% CI: −0.007 to −0.001; P = 0.02; β_DBP = −0.003; 95% CI: −0.006 to −0.001; P = 0.01). Higher UA concentrations were associated with higher SBP levels only in overweight/obese women (β = 3.878; 95% CI: 0.687–7.068), whereas higher CRP concentrations (≥2.6 mg/L) were associated with higher DBP in under/normal weight women (β =2.252; 95% CI: 0.267–4.236).ALP, ALT, and Cr concentrations were positively associated with BP levels, whereas ALP was associated with a lower rate of change in BP. The associations of UA and CRP with BP differ according to the early-pregnancy BMI.     

FN14 and GRP94 expression are prognostic/predictive biomarkers of brain metastasis outcome that open up new therapeutic strategies

Brain metastasis is a devastating problem in patients with breast, lung and melanoma tumors. GRP94 and FN14 are predictive biomarkers over-expressed in primary breast carcinomas that metastasized in brain. To further validate these brain metastasis biomarkers, we performed a multicenter study including 318 patients with breast carcinomas. Among these patients, there were 138 patients with metastasis, of whom 84 had brain metastasis. The likelihood of developing brain metastasis increased by 5.24-fold (95%CI 2.83–9.71) and 2.55- (95%CI 1.52–4.3) in the presence of FN14 and GRP94, respectively. Moreover, FN14 was more sensitive than ErbB2 (38.27 vs. 24.68) with similar specificity (89.43 vs. 89.55) to predict brain metastasis and had identical prognostic value than triple negative patients (p < 0.0001). Furthermore, we used GRP94 and FN14 pathways and GUILD, a network-based disease-gene prioritization program, to pinpoint the genes likely to be therapeutic targets, which resulted in FN14 as the main modulator and thalidomide as the best scored drug. The treatment of mice with brain metastasis improves survival decreasing reactive astrocytes and angiogenesis, and down-regulate FN14 and its ligand TWEAK. In conclusion our results indicate that FN14 and GRP94 are prediction/prognosis markers which open up new possibilities for preventing/treating brain metastasis.     

Alveolar corticotomies for accelerated orthodontics: A systematic review

Introduction

It has been suggested that alveolar corticotomies may accelerate tooth movement, broaden the scope of malocclusion types that can be treated orthodontically, decrease the need for extractions, and support long-term stability. Several techniques have been proposed, although the indications, ideal design and technical characteristics, potential complications, and objective clinician and patient satisfaction remain unclear. This systematic review aimed to provide scientific support to validate alveolar corticotomies as a reliable approach to accelerated orthodontics.

Preclinical randomized controlled trial of bilateral discectomy versus bilateral discopexy in Black Merino sheep temporomandibular joint: TEMPOJIMS – Phase 1- histologic,imaging and body weight results

Introduction

The role of temporomandibular joint (TMJ) surgery is not well defined due to a lack of quality randomized controlled clinical trials, comparing different TMJ surgical treatments with medical and placebo interventions. The temporomandibular joint interposal study (TEMPOJIMS) is a rigorous preclinical trial divided in 2 phases. In phase 1 the authors investigated the role of the TMJ disc and in phase 2 the authors evaluated 3 different interposal materials. The present work of TEMPOJIMS – phase 1, aims to evaluate histopathologic and imaging changes of bilateral discectomy and discopexy in Black Merino sheep TMJ, using a high-quality trial following the ARRIVE guidelines.

Sonographic criteria for therapy follow-up in the course of ultrasound-guided intra-articular injections of hyaluronic acid in hand osteoarthritis

Objective

To assess the value of sonographic criteria, based on measurements of joint capsule distension and synovial hyperemia, during the course of repeated ultrasound (US)-guided intra-articular injections of hyaluronic acid (HA) in hand osteoarthritis (OA).

Materials and methods

Thirty-three patients (28 females/5 males), with hand OA in 78 joints, were included in this study. Patients underwent sonographic evaluation at baseline and consecutively for 4 weeks at weekly US-guided intra-articular injections of HA (Hyalgan^®). Measurements of joint thickening and joint inflammation were performed with Grey-scale and semi-quantitative Power-Doppler US (PDUS). Sonographic values were correlated with weekly patients self-assessment of pain for each treated joint.

Results

The mean (SD) patients self-assessment of pain statistically significantly (p < 0.0001) decreased from the first [68.3(22.3)] to the last week [37.3(30.34)]. A steady pain relief could be noticed in 67 (86%) of all treated joints. Over the whole observation period, the mean (SD) joint thickening of all joints markedly decreased from 15.6 mm (5.3) to 13.1 mm (6.4) (p < 0.0001). The PDUS-score before initiation of HA treatment was statistically significantly higher than at the end of therapy (p < 0.0001). The decrease in pain statistically significantly correlated with the decrease of joint thickening and PDUS-score between baseline and the end of therapy (p < 0.001).

Conclusion

In this study, we demonstrate the meaningfulness of sonographic evaluation criteria including measurements of joint capsule distension and PDUS vascularization, both significantly correlating with the decrease of pain, during the therapy follow-up of US-guided intra-articular HA-injections in patients with hand OA.     

The Size 1 ProSeal™ laryngeal mask airway in infants: a randomized,noncrossover study with the Classic™ laryngeal mask airway

Background: In recent years, numerous scientific publications have endorsed the superiority of the ProSeal? laryngeal mask airway (PLMA) over the Classic? laryngeal mask airway (cLMA) in adults, children, and infants. The PLMA forms a better seal for both the respiratory and gastrointestinal tracts, provides easier access to the gastrointestinal tract, and exerts lower mucosal pressures for a given seal pressure. This study aims to determine whether this superiority can also be observed for the size 1 PLMA used in anesthetized neonates and infants with positive pressure ventilation. Methods: Sixty consecutive neonates and infants undergoing elective surgical procedures were randomized to airway management with the size 1 PLMA or cLMA. For all patients, we recorded ease of insertion, effective airway time, number of placement attempts, oropharyngeal leak pressure, fiberoptic position, audible leaks, mask displacement, number of reinsertions during maintenance, gastric insufflation, and frequency of blood stain. Results: Ease of insertion, successful insertion in <3 attempts, fiberoptic position of the airway tube, and frequency of blood stain were similar in both groups. Effective airway time was lower for the PLMA group (30.5 vs 35.6 s). Oropharyngeal leak pressure was higher with the PLMA (32.9 vs 22.2 cm H₂O, P < 0.001) and gastric insufflation less common (0% vs 6%, P = 0.492). There were fewer mask displacements during maintenance of anesthesia with the PLMA (0% vs 26.7%, P < 0.001). Mask reinsertion was not necessary during maintenance of anesthesia with the PLMA, although it was necessary in 14 cases in the cLMA group (0% vs 46%, P < 0.001). Audible leaks were less common with the PLMA (0% vs 46%, P < 0.001). Conclusions: We conclude that the size 1 PLMA is a stable, safe, and efficacious airway control device during neonatal and infant anesthesia, allowing higher peak airway pressure during positive pressure ventilation, with fewer mask displacements and gastric insufflations than the cLMA.