Modelling hypercholesterolaemia in rats using high cholesterol diet

Hypercholesterolaemia is a complex condition with multiple causes, including both lifestyle and genetic aspects. It is also a risk factor for cardiovascular diseases (CVDs), which are responsible for 172 million deaths/year. Although the reasons for hypercholesterolaemia are known, there are many critical questions that remain to be answered so that new therapeutics can be developed. In order to elucidate the pathobiology of this condition, animal models can mimic the pathology of human hypercholesterolaemia. One example of an animal model is induced by the hypercholesterolaemic diet in Wistar rats. The present review first summarizes the current understanding of the metabolic profile involved in hypercholesterolaemia in humans. Next it comments about the lack of consensus as to which hypercholesterolaemia induction protocol should be used. The present work aimed to review experimental studies that induced hypercholesterolaemia in Wistar rats it was not intended to judge the “best” model, since they all achieved the goal of inducing an increase in serum cholesterol.     

National Italian Guidelines for caries prevention in 0 to 12 years-old children.

AIM: Oral and dental health improved tremendously over the last fifty years in Italy but still prevalence of dental caries in children remains a significant clinical problem. This report describes the National Italian Guidelines for caries prevention. METHODOLOGY: A panel of experts coordinated by the Italian Society of Paediatric Dentistry (SIOI) planned to elaborate the national Italian guidelines for caries prevention in children. The structure of the guidelines has been planned to follow the principles of modern caries treatment and management as well as science based dentistry. The main procedure was based on a hierarchic evaluation of literature. CONCLUSION: The guidelines are planned for dentist working in primary dental care, however, they are also designed to be of interest for other care professionals such as paediatricians, gynecologists, pharmacists and general medical practitioners and also for parents and/or guardians of the children.     

Some tools for the identification of high caries risk individuals. A review

As a consequence of the polarisation of dental caries, which occurred over the last 3 decades in industrialised countries, the usefulness of risk assessment, both for individuals and for groups of subjects, became evident. At individual level, the early identification of high and medium caries-risk subjects allows to plan specific preventive measures for each subject's needs, based on the risk grade and the causally-directed diagnosis. At population level, risk assessment helps to increase the efficiency and to reduce the costs of caries preventive programmes. In this study, a review of caries-risk indicators is proposed: these indicators, collected through the analysis of relevant background data, clinical examination and salivary tests are indispensable to achieve a correct caries-risk assessment. A review of the studies on the attempts to produce prediction models for caries-risk assessment is presented: in view of the multifactorial nature of caries etiology and the complexity of the prediction of individual caries-risk, a multivariate approach is necessary. Finally, some suggestions on the clinical usefulness and on indications of caries-risk determination are given.     

Can we withdraw immunosuppressants in patients with lupus nephritis in remission? An expert debate

Lupus nephritis (LN) treatment requires an initial intensive period of therapy followed by a long-term maintenance treatment in order to stabilize disease control and eventually reach renal remission. In this section, Authors discuss the feasibility of safely lowering and even suspending maintenance therapy in LN patients having entered remission, highlighting hurdles in predicting the depth and durability of disease quiescence together with the need for minimizing potentially toxic therapies. Even though no firm conclusions can still be drawn, the treating physician has to find the wise balance between disease control and treatment-related drawbacks by following patients closely and recognizing as early as possible the ones who are likely to reach a deep and durable renal remission; there is consensus that is these are the only patients in whom a potential safe complete withdrawal can be foreseen so far.     

Lung injury induced by sepsis: lessons learned from large animal models and future directions for treatment

Acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS) remain common complications of sepsis. Unfortunately, development of effective pharmacologic and ventilatory treatment strategies for sepsis-induced ALI/ARDS has not made significant progress over the past several decades. One of the major reasons for this conundrum involves the animal models used as platforms for testing new treatment strategies. High-fidelity, clinically translational, large animal models are essential for developing treatments that will ultimately be successful in human clinical trials. Additionally, treatment strategies purely based on pharmacologic intervention are largely destined for failure as the redundancies in the systemic inflammatory response largely negate the effectiveness of a single-action drug. Conversely, a treatment strategy based on the appropriate use of mechanical ventilation affects lung physiology on a breath-to-breath basis and has the potential to treat, and even prevent, the ALI/ARDS associated with sepsis.     

Alveolar inflation during generation of a quasi-static pressure/volume curve in the acutely injured lung

OBJECTIVE: Lower and upper inflection points on the quasi-static curve representing a composite of pressure/volume from the whole lung are hypothesized to represent initial alveolar recruitment and overdistension, respectively, and are currently utilized to adjust mechanical ventilation in patients with acute respiratory distress syndrome. However, alveoli have never been directly observed during the generation of a pressure/volume curve to confirm this hypothesis. In this study, we visualized the inflation of individual alveoli during the generation of a pressure/volume curve by direct visualization using in vivo microscopy in a surfactant deactivation model of lung injury in pigs. DESIGN: Prospective, observational, controlled study. SETTING: University research laboratory. SUBJECTS: Eight adult pigs. INTERVENTIONS: Pigs were anesthetized and administered mechanical ventilation, underwent a left thoracotomy, and were separated into two groups: control pigs (n = 3) were subjected to surgical intervention, and Tween lavage pigs (n = 5) were subjected to surgical intervention plus surfactant deactivation by Tween lavage (1.5 mL/kg 5% solution of Tween in saline). The microscope was then attached to the lung, and the size of each was alveolus quantified by measuring the alveolar area by computer image analysis. Each alveolus in the microscopic field was assigned to one of three types, based on alveolar mechanics: type I, no visible change in alveolar size during ventilation; type II, alveoli visibly change size during ventilation but do not totally collapse at end expiration; and type III, alveoli visibly change size during tidal ventilation and completely collapse at end expiration. After alveolar classification, the animals were disconnected from the ventilator and attached to a super syringe filled with 100% oxygen. The lung was inflated from 0 to 220 mL in 20-mL increments with a 10-sec pause between increments for airway pressure and alveolar confirmation to stabilize. These data were utilized to generate both quasi-static pressure/volume curves and individual alveolar pressure/area curves. MEASUREMENTS AND MAIN RESULTS: The normal lung quasi-static pressure/volume curve has a single lower inflection point, whereas the curve after Tween has an inflection point at 8 mm Hg and a second at 24 mm Hg. Normal alveoli in the control group are all type I and do not change size appreciably during generation of the quasi-static pressure/volume curve. Surfactant deactivation causes a heterogenous injury, with all three alveolar types present in the same microscopic field. The inflation pattern of each alveolar type after surfactant deactivation by Tween was notably different. Type I alveoli in either the control or Tween group demonstrated minimal change in alveolar area with lung inflation. Type I alveolar area was significantly (p <.05) larger in the control as compared with the Tween group. In the Tween group, type II alveoli increased significantly in area, with lung inflation from 0 mL (9666 +/- 1340 microm2) to 40 mL (12,935 +/- 1725 microm2) but did not increase further (220 mL, 14,058 +/- 1740 microm2) with lung inflation. Type III alveoli initially recruited with a relatively small area (20 mL lung volume, 798 +/- 797 microm2) and progressively increased in area throughout lung inflation (120 mL, 7302 +/- 1405 microm2; 220 mL, 11,460 +/- 1078 microm2) CONCLUSION: The normal lung does not increase in volume by simple isotropic (balloon-like) expansion of alveoli, as evidenced by the horizontal (no change in alveolar area with increases in airway pressure) pressure/area curve. After surfactant deactivation, the alveolar inflation pattern becomes very complex, with each alveolar type (I, II, and III) displaying a distinct pattern. None of the alveolar pressure/area curves directly parallel the quasi-static lung pressure/volume curve. Of the 16, only one type III atelectatic alveolus recruited at the first inflection point and only five recruited concomitant with the second inflation point, suggesting that neither inflection point was due to inflection point was due to massive alveolar recruitment. Thus, the components responsible for the shape of the pressure/volume curve include all of the individual alveolar pressure/area curves, plus changes in alveolar duct and airway size, and the elastic forces in the pulmonary parenchyma and the chest wall.     

Unilateral Direct Carotid Cavernous Fistula Causing Bilateral Ocular Manifestation

Unilateral carotid cavernous fistula presents with ipsilateral ocular findings. Bilateral presentation is only seen in bilateral fistulas, usually associated with indirect (dural) carotid cavernous fistulas. Direct carotid cavernous fistulas are an abnormal communication between the internal carotid artery and the cavernous sinus. They typically begin with a traumatic disruption in the artery wall into the cavernous sinus, presenting with a classic triad of unilateral pulsatile exophthalmos, cranial bruit and episcleral venous engorgement. We report the case of a 38-year-old male with traumatic right carotid cavernous sinus fistula and bilateral ocular presentation successfully treated by interventional neuroradiology.Key Words: Exophthalmos, Papilledema, Carotid artery injury, Carotid cavernous sinus fistula, Endovascular procedure, Therapeutic embolization