Cilastatin as a Potential Anti-Inflammatory and Neuroprotective Treatment in the Management of Glaucoma.

Glaucoma is a neurodegenerative disease that causes blindness. In this study, we aimed to evaluate the protective role of cilastatin (CIL), generally used in the treatment of nephropathologies associated with inflammation, in an experimental mouse model based on unilateral (left) laser-induced ocular hypertension (OHT). Male Swiss mice were administered CIL daily (300 mg/kg, i.p.) two days before OHT surgery until sacrifice 3 or 7 days later. Intraocular Pressure (IOP), as well as retinal ganglion cell (RGC) survival, was registered, and the inflammatory responses of macroglial and microglial cells were studied via immunohistochemical techniques. Results from OHT eyes were compared to normotensive contralateral (CONTRA) and naïve control eyes considering nine retinal areas and all retinal layers. OHT successfully increased IOP values in OHT eyes but not in CONTRA eyes; CIL did not affect IOP values. Surgery induced a higher loss of RGCs in OHT eyes than in CONTRA eyes, while CIL attenuated this loss. Similarly, surgery increased macroglial and microglial activation in OHT eyes and to a lesser extent in CONTRA eyes; CIL prevented both macroglial and microglial activation in OHT and CONTRA eyes. Therefore, CIL arises as a potential effective strategy to reduce OHT-associated damage in the retina of experimental mice.

Age-Related Retinal Layer Thickness Changes Measured by OCT in APPNL-F/NL-F Mice: Implications for Alzheimer's Disease.

In Alzheimer's disease (AD), transgenic mouse models have established links between abnormalities in the retina and those in the brain. APPNL-F/NL-F is a murine, humanized AD model that replicates several pathological features observed in patients with AD. Research has focused on obtaining quantitative parameters from optical coherence tomography (OCT) in AD. The aim of this study was to analyze, in a transversal case-control study using manual retinal segmentation via SD-OCT, the changes occurring in the retinal layers of the APPNL/F-NF/L AD model in comparison to C57BL/6J mice (WT) at 6, 9, 12, 15, 17, and 20 months of age. The analysis focused on retinal thickness in RNFL-GCL, IPL, INL, OPL, and ONL based on the Early Treatment Diabetic Retinopathy Study (ETDRS) sectors. Both APPNL-F/NL-F-model and WT animals exhibited thickness changes at the time points studied. While WT showed significant changes in INL, OPL, and ONL, the AD model showed changes in all retinal layers analyzed. The APPNL-F/NL-F displayed significant thickness variations in the analyzed layers except for the IPL compared to related WT. These thickness changes closely resembled those found in humans during preclinical stages, as well as during mild and moderate AD stages, making this AD model behave more similarly to the disease in humans.

OCT Imaging in Murine Models of Alzheimer's Disease in a Systematic Review: Findings, Methodology and Future Perspectives.

The murine models of Alzheimer's disease (AD) have advanced our understanding of the pathophysiology. In vivo studies of the retina using optical coherence tomography (OCT) have complemented histological methods; however, the lack of standardisation in OCT methodologies for murine models of AD has led to significant variations in the results of different studies. A literature search in PubMed and Scopus has been performed to review the different methods used in these models using OCT and to analyse the methodological characteristics of each study. In addition, some recommendations are offered to overcome the challenges of using OCT in murine models. The results reveal a lack of consensus on OCT device use, retinal area analysed, segmentation techniques, and analysis software. Although some studies use the same OCT device, variations in other parameters make the direct comparison of results difficult. Standardisation of retinal analysis criteria in murine models of AD using OCT is crucial to ensure consistent and comparable results. This implies the application of uniform measurement and segmentation protocols. Despite the absence of standardisation, OCT has proven valuable in advancing our understanding of the pathophysiology of AD.

Glaucoma: from pathogenic mechanisms to retinal glial cell response to damage.

Glaucoma is a neurodegenerative disease of the retina characterized by the irreversible loss of retinal ganglion cells (RGCs) leading to visual loss. Degeneration of RGCs and loss of their axons, as well as damage and remodeling of the lamina cribrosa are the main events in the pathogenesis of glaucoma. Different molecular pathways are involved in RGC death, which are triggered and exacerbated as a consequence of a number of risk factors such as elevated intraocular pressure (IOP), age, ocular biomechanics, or low ocular perfusion pressure. Increased IOP is one of the most important risk factors associated with this pathology and the only one for which treatment is currently available, nevertheless, on many cases the progression of the disease continues, despite IOP control. Thus, the IOP elevation is not the only trigger of glaucomatous damage, showing the evidence that other factors can induce RGCs death in this pathology, would be involved in the advance of glaucomatous neurodegeneration. The underlying mechanisms driving the neurodegenerative process in glaucoma include ischemia/hypoxia, mitochondrial dysfunction, oxidative stress and neuroinflammation. In glaucoma, like as other neurodegenerative disorders, the immune system is involved and immunoregulation is conducted mainly by glial cells, microglia, astrocytes, and Müller cells. The increase in IOP produces the activation of glial cells in the retinal tissue. Chronic activation of glial cells in glaucoma may provoke a proinflammatory state at the retinal level inducing blood retinal barrier disruption and RGCs death. The modulation of the immune response in glaucoma as well as the activation of glial cells constitute an interesting new approach in the treatment of glaucoma.

Retinal Vascular and Structural Changes in the Murine Alzheimer's APPNL-F/NL-F Model from 6 to 20 Months.

Alzheimer's disease (AD) may manifest retinal changes preceding brain pathology. A transversal case-control study utilized spectral-domain OCT angiography (SD-OCTA) and Angio-Tool software 0.6a to assess retinal vascular structures and OCT for inner and outer retina thickness in the APPNL-F/NL-F AD model at 6, 9, 12, 15, 17, and 20 months old. Comparisons to age-matched wild type (WT) were performed. The analysis focused on the three vascular plexuses using AngiooTool and on retinal thickness, which was represented with the Early Treatment Diabetic Retinopathy Study (ETDRS) sectors. Compared to WT, the APPNL-F/NL-F group exhibited both vascular and structural changes as early as 6 months persisting and evolving at 15, 17, and 20 months. Significant vascular alterations, principally in the superficial vascular complex (SVC), were observed. There was a significant decrease in the vessel area and the total vessel length in SVC, intermediate, and deep capillary plexus. The inner retina in the APPNL-F/NL-F group predominantly decreased in thickness while the outer retina showed increased thickness in most analyzed time points compared to the control group. There are early vascular and structural retinal changes that precede the cognitive changes, which appear at later stages. Therefore, the natural history of the APPNL-F/NL-F model may be more similar to human AD than other transgenic models.

Cirugía de elongación intestinal tipo "Step", en paciente con síndrome de intestino corto y enfermedad de Crohn. Primer caso realizado en Venezuela / Intestinal elongation surgery (step procedure) in a patient with short bowel syndrome and crohn disease. First case done in Venezuela

En el síndrome de intestino corto-insuficiencia intestinal, uno de los principales factores pronóstico, es la longitud intestinal residual, por lo que estrategias quirúrgicas que permitan aumentar la longitud cobran relevar importancia en el proceso de adaptación y eventual autonomía intestinal.Caso clínico: Paciente femenina, portadora de enfermedad de Crohn, con antecedentes de resección masiva de intestino por cuadro hemorrágico, se evidencia en el estudio radiológico moderada dilatación de asas delgadas, por lo que se practica cirugía de elongación intestinal tipo STEP, pudiendo aumentar la longitud intestinal de 32cm a 54cm. Resultados:Tiempo operatorio 270 min, período de seguimiento 10 meses, recuperación nutricional de 14,48 IMC a 22,5 IMC,con un esquema nutricional actual de 3 veces a la semana de 12 horas de administración(AU)

In the short bowel syndrome-intestinal failure, one of the most important key factors is the intestinal measure, so the surgical strategy searching to improve intestinal length is very important in order to facilitate the intestinal adaptation process. Clinic presentation: Female patient, with Crohn disease, previou surgery: massive intestinal resection due to hemorrhage. On intestinal X ray was observed mild dilated jejunum. It was performed intestinal lengthening surgery (STEP procedure). Intestinal length previous surgery 32cm, after procedure 54cm. Results: Operative time 27 min, follow up 10 months, nutritional recover IMC 14,48 to 22,5 Kg/m2 , nutritional therapy: 3 days/week TPN(AU)

Tratamiento de la displasia mamaria atípica con tamoxifeno como profilaxis del cáncer de mama en Santiago de Cuba / Treatment of the atypical mammary dysplasia with tamoxifeno as prophylaxis of breast cancer in Santiago de Cuba

Se realizó un estudio retrospectivo de 7 años (2001 – 2007) en la consulta especializada de mastología del Hospital Provincial Docente Saturnino Lora Torres de Santiago de Cuba, radicada en el Policlínico de Especialidades perteneciente a dicha institución. Se obtuvieron los datos clínicos de 164 pacientes con displasia mamaria de diferentes grados y alta predisposición a padecer cáncer, las cuales eran tratadas y consultadas bimensualmente por cirujanos, quienes concluyeron que el control hormonal y el examen periódico de las mujeres afectadas, mejoraron el pronóstico e incrementaron los índices de curación.

A 7 year-old retrospective study (2001 - 2007) was carried out in the breast specialized department from Saturnino Lora Torres Teaching Provincial Hospital from Santiago de Cuba, sited in the Specialties Polyclinic belonging to this institution. The clinical data of 164 patients with mammary dysplasia of different grades and high predisposition to suffer from cancer, who were treated and examined every two months by surgeons were obtained. They concluded that the hormonal control and the periodic examination of the affected women, improved the prognosis and increased the cure rates.