Visual Function Improvement after Plasma Exchange Therapy for Acute Optic Neuritis in Neuromyelitis Optica Spectrum Disorders: Case Series and Review.

OBJECTIVE: Neuromyelitis optica (NMO) and neuromyelitis optica spectrum disorder (NMOSD) are autoimmune-mediated central nervous system disorders distinguished by the presence of serum aquaporine-4 IgG antibody (AQP4-Ab). The clinical panel comprises severe optic neuritis (ON) and transverse myelitis, which can result in incomplete recovery and a high risk of recurrence. METHODS: This study aimed to evaluate the visual outcomes of three patients with severe acute ON in NMOSD that was non-responsive to intravenous methylprednisolone (IVMP), who received plasma exchange therapy (PLEX). We included three patients (P1, P2 and P3) with severe acute ON who had no improvement after IVMP treatment and were admitted to the ophthalmology department at the Emergency University Hospital Bucharest from January 2022 to September 2023. All three patients with ON were diagnosed in accordance with the criteria described by the Optic Neuritis Treatment Trial. All the subjects were experiencing their first attack. RESULTS: The mean recruitment age was 35.3 ± 7.71. All patients were seropositive for the AQP4 antibody. All patients were tested for serum myelin oligodendrocyte glycoprotein (MOG) antibody but only one showed a positive test (P3). Lesions visible in orbital MRI indicated the involvement of retrobulbar, canalicular and/or intracranial segments. All three subjects had no response or incomplete remission after an IVMP protocol (5 days of 1000 mg intravenous methylprednisolone in sodium chloride 0.9%). The mean time from onset of optic neuritis to PLEX was 37.6 days. The PLEX treatment protocol comprised five cycles of plasma exchange treatment over 10 days, with a plasma exchange session every other day. An amount of 1 to 1.5 volumes of circulating plasma were dialyzed for 2-4 h. At 1 month after the completion of PLEX therapy, BCVA and VF parameters were improved in all three patients. CONCLUSION: The treatment of ON remains subject to debate and is somewhat controversial. Plasma exchange must be considered as a rescue therapy when IVMP is insufficient for AQP4-ON patients. This study revealed that PLEX treatment effectively improves the visual outcomes of patients experiencing their first attack of severe acute isolated ON after high-dose IVMP treatment. This study suggests that PLEX may be associated with improved visual outcomes in NMOSD acute optic neuritis.

Callers' Descriptions of Stroke Symptoms during Emergency Calls in Victims Who Have Fallen or Been Found Lying Down: A Qualitative Content Analysis.

Early identification of stroke symptoms is essential. The rate of stroke identification by call-takers at emergency medical communication centres (EMCCs) varies, and patients who are found in a lying down position are often not identified as having an ongoing stroke. OBJECTIVES: this study aimed to explore signs and symptoms of stroke in patients who had fallen or were found in a lying position. DESIGN: a retrospective exploratory qualitative study design was used. METHOD: a total of 29 emergency calls to EMCCs regarding patients discharged with a stroke diagnosis from a large teaching hospital in Stockholm, Sweden, in January-June 2011, were analysed using qualitative content analysis. RESULTS: during the emergency calls, the callers described a sudden change in the patient's health status including signs such as the patient's loss of bodily control, the patient's perception of a change in sensory perception, and the callers' inability to communicate with the patient. CONCLUSIONS: The callers' descriptions of stroke in a person found in a lying position are not always as described in assessment protocols describing the onset of a stroke. Instead, the symptom descriptions are much vaguer. Therefore, to increase identification of stroke during emergency calls, there is a need for an increased understanding of how callers describe stroke symptoms and communicate with the call-takers.

Uncommon association between vascular Ehlers-Danlos syndrome and ocular complications.

Ehlers-Danlos syndromes (EDS) represent a group of rare inherited disorders that affect connective tissues. There are 13 types of disease, most of them affecting joints or skin; symptoms usually include loose joints, joint pain, stretchy velvety skin, abnormal scar formation. However, the most serious type of disease is vascular EDS (vEDS), or EDS type 4 because patients may suffer vessels dissections or internal organs lesions, followed by bleeding, which endangers patient's life, but also thromboembolic events. We present two clinical cases of vEDS managed in our clinic in 1 year distance. In both cases, patients were active young persons (in their thirties, and respectively, twenties), both with multiple non-traumatic vascular dissections, and severe ocular complications: arterio-venous fistula with massive exophthalmia, and central retinal artery occlusion, respectively. Both cases were challenging since the life of the patients were threatened by their condition. However, in both cases, prompt treatment and finding the right trigger of the ocular pathology and vascular injuries helped doctors to provide proper and prompt medical care, in order to prevent future similar events to happen and to preserve a good quality of life for these patients.

Highlights on Genetic Polymorphism Associated with Thromboembolic Risk; Implications in Ophthalmic and Autoimmune Disorders-A Review.

The present paper explores genetic polymorphism and its association with thromboembolic retinal venous disorders, such as central/hemi-retinal vein occlusion, as well as possible correlations with other ocular findings, such as closed angle glaucoma, but also with autoimmune general disorders. In this review, we are highlighting the importance of establishing a correspondence between all of the above, since they all have complex etiopathogeneses; sometimes, when all coexist together, they could generate effects that may be very difficult to manage. There are studies supporting that genetic polymorphism, such as the variant MTHFR A1298C, may increase the risk for developing glaucoma, especially in the heterozygote model. Being aware of all these aspects may prove to be useful in patients with several associated diseases, as a combined effort between several medical specialties may prove to the benefit of these patients. Our review, completed with an exemplifying clinical case, shows that it is necessary to raise awareness of all aspects of a complex medical situation, including the genetic one, of a patient being at risk for thromboembolic episodes, for preventing them or managing them promptly and properly in the future.

Anti-staphylococcal activity and mode of action of thioridazine photoproducts.

Antibiotic resistance became an increasing risk for population health threatening our ability to fight infectious diseases. The objective of this study was to evaluate the activity of laser irradiated thioridazine (TZ) against clinically-relevant bacteria in view to fight antibiotic resistance. TZ in ultrapure water solutions was irradiated (1-240 min) with 266 nm pulsed laser radiation. Irradiated solutions were characterized by UV-Vis and FTIR absorption spectroscopy, thin layer chromatography, laser-induced fluorescence, and dynamic surface tension measurements. Molecular docking studies were made to evaluate the molecular mechanisms of photoproducts action against Staphylococcus aureus and MRSA. More general, solutions were evaluated for their antimicrobial and efflux inhibitory activity against a panel of bacteria of clinical relevance. We observed an enhanced antimicrobial activity of TZ photoproducts against Gram-positive bacteria. This was higher than ciprofloxacin effects for methicillin- and ciprofloxacin-resistant Staphylococcus aureus. Molecular docking showed the Penicillin-binding proteins PBP3 and PBP2a inhibition by sulforidazine as a possible mechanism of action against Staphylococcus aureus and MRSA strains, respectively. Irradiated TZ reveals possible advantages in the treatment of infectious diseases produced by antibiotic-resistant Gram-positive bacteria. TZ repurposing and its photoproducts, obtained by laser irradiation, show accelerated and low-costs of development if compared to chemical synthesis.

Laser irradiated phenothiazines: New potential treatment for COVID-19 explored by molecular docking.

The worldwide infection with the new Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) demands urgently new potent treatment(s). In this study we predict, using molecular docking, the binding affinity of 15 phenothiazines (antihistaminic and antipsychotic drugs) when interacting with the main protease (Mpro) of SARS-CoV-2. Additionally, we tested the binding affinity of photoproducts identified after irradiation of phenothiazines with Nd:YAG laser beam at 266 nm respectively 355 nm. Our results reveal that thioridazine and its identified photoproducts (mesoridazine and sulforidazine) have high biological activity on the virus Mpro. This shows that thioridazine and its two photoproducts might represent new potent medicines to be used for treatment in this outbreak. Such results recommend these medicines for further tests on cell cultures infected with SARS-CoV-2 or animal model. The transition to human subjects of the suggested treatment will be smooth due to the fact that the drugs are already available on the market.

Spectroscopic Characterization of Emulsions Generated with a New Laser-Assisted Device.

This paper presents a spectroscopic study of emulsions generated with a laser-assisted device. Fourier transform infrared (FTIR), Raman and UV-Vis-NIR reflectance spectra of emulsions, recorded before and after exposure to laser radiation were used to characterize the effect of laser irradiation. The paper also presents a comparison between the calculated IR spectra and the experimental FTIR spectra of an emulsion's components. FTIR measurements allowed the identification of absorption bands specific to each of the emulsions' components. Moreover, it enabled the observation of destabilization of the emulsion in real-time. Raman spectroscopy allowed the observation of the modifications at a molecular level, by identifying the vibrations of the representative functional groups and the polymerization of sodium tetradecyl sulfate (STS) molecules by analyzing the evolution of the carbonyl band. UV-Vis-NIR reflectance spectra of emulsions before and after exposure to laser radiation showed that the physical characteristics of the emulsions changed during irradiation-the dimensions of the droplets decreased, leading to an emulsion with a better time stability. These results proved that the employed spectroscopy techniques were powerful tools in emulsion analysis.

Necrotizing retinitis of multifactorial etiology.

Introduction. We present the case of a 73-year-old woman with osteoporosis, who presented to the emergency room with a sudden vision loss and ocular pain in the right eye, which appeared two days before. The patient mentioned loss of appetite, weight loss for three months and low fever for two weeks. Materials and methods. Among the ophthalmological findings, the most important were panuveitis, and large confluent necrotic areas in the peripheral retina. The patient was diagnosed with RE Panuveitis and acute necrotizing retinitis. Results. Blood exams showed leukocytosis and monocytosis, thrombocytosis and anemia. Further investigations showed high levels of Cytomegalovirus (CMV) anti IgG and Herpes Simplex (HS) type 1 virus anti IgM, urinary infection, and secondary hepatic cytolysis. The CT and MRI of the thorax and abdomen showed no sign of neoplastic disease, and no explanation for the CMV infection was found. The patient received general corticotherapy and antiviral therapy, and, after one month, RE BCVA was 20/ 30. Particularity of the case. Acute necrotizing retinitis in an old patient with CMV and HSV type 1, associated with secondary hepatic cytolysis, without any other immunosuppressive disease and very good outcome.

FIGHTING MULTIPLE DRUG RESISTANCE: EFFECTS OF UV-ACTIVATED CHLORPROMAZINE ON RABBIT'S EYE PSEUDOTUMOURS.

INTRODUCTION: Multiple drug resistance requires a flexible approach to find medicines able to overcome it. One method could be the exposure of existing medicines to UV laser beams to generate active photoproducts against bacteria and/or malignant tumors. METHODS: The interaction of Chlorpromazine (CPZ) (irradiated with 266 nm pulsed laser beams) was studied at concentrations of 10 mg/ml and 20 mg/ ml in ultrapure water, with pseudotumors of rabbits eyes. RESULTS: The use of CPZ water solution exposed to 266 nm in the treatment of pseudotumor tissues produced on rabbit eyes showed that treatment results depend on initial (before irradiation) CPZ concentration and exposure time. At this stage, one could not specify which out of the generated photoproducts, individual or as a group, was/were efficient in pseudotumor cure but overall effects were observable. Application of CPZ irradiated solutions on rabbit eyes pseudotumors seemed to produce a faster recovery of tissues with respect to control, untreated eyes. CONCLUSIONS: Histologic findings in the treated tissues showed a good anti-inflammatory response. The results obtained open perspectives to fight MDR and/or development of pseudotumoral processes with substances that were not initially made for this purpose (non-antibiotics, for instance).

Claudin expression profile separates Alzheimer's disease cases from normal aging and from vascular dementia cases.

We have reported earlier that tight-junction proteins are detectable by standard immunohistochemistry in the brain parenchyma, namely in the cell bodies of neurons, astrocytes, and oligodendrocytes. Here we show, by projection to latent structures - discriminate analysis (PLS-DA), that the immunohistochemical detection profile of tight junction proteins clearly distinguishes the AD cases from healthy aging controls and from the cases of dementia with a predominantly vascular pathology underlying the symptoms (vascular dementia, VaD; cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, CADASIL; and cerebral amyloid angiopathy, CAA). Our findings might be valuable in the perspective of developing biomarkers for AD.

Laser-induced autofluorescence measurements on brain tissues.

It was demonstrated that comparison of the autofluorescence spectra induced with laser radiation in ultraviolet and visible allows the identification of brain tumor tissues and normal tissues as well as the difference between them. The measurements were performed on homogenates to ensure an optimal reproducibility of the results. We conclude that the autofluorescence spectra of the tumor samples are close to those measured for normal tissues, but there are differences between them that allow distinguishing the tumor from the normal tissue. One difference is that for each pair of tumor/normal tissue samples, the peak autofluorescence for the normal tissue is shifted with respect to that for the tumor-typically between 10 and 20 nm; overall autofluorescence intensity is also different for the components of the same pair, the difference being in the range 15%-30%. A parameter that can also be used is the variation of the ratio of some fluorescence intensity peaks between normal and tumor tissue samples. Measurements of this parameter yielded variations ranging between 10% and 40%. Another conclusion of the study is that in vitro experiments show that it is mandatory to use pairs of samples (normal/tumor tissue) taken from the same patient. The results show that, after further experimental in vitro tests, the method may be adapted to real-time intraoperative conditions by measuring the autofluorescence of the tumor and of the adjacent normal tissue.

Occludin is overexpressed in Alzheimer's disease and vascular dementia.

The tight junctions (TJs) are key players in the control of blood-brain barrier (BBB) properties, the most complex TJs in the vascular system being found in the endothelial cells of brain capillaries. One of the main TJs proteins is occludin, which anchors plasma membranes of neighbour cells and is present in large amounts in the brain endothelia. Previous studies demonstrated that disruption of BBB in various pathological situations associates with changes in occludin expression, and this change could be responsible for malfunction of BBB. Therefore in this study, applying an immunohistochemical approach, we decided to explore the occludin expression in frontal cortex (FC) and basal ganglia in ageing control, Alzheimer's disease (AD), and vascular dementia (VD) brains, as far as all these pathologies associate microangiopathy and disruption of BBB. Strikingly, we found selected neurons, astrocytes and oligodendrocytes expressing occludin, in all cases studied. To estimate the number of occludin-expressing neurons, we applied a stereological approach with random systematic sampling and the unbiased optical fractionator method. We report here a significant increase in ratio of occludin-expressing neurons in FC and basal ganglia regions in both AD and VD as compared to ageing controls. Within the cerebral cortex, occludin was selectively expressed by pyramidal neurons, which are the ones responsible for cognitive processes and affected by AD pathology. Our findings could be important in unravelling new pathogenic pathways in dementia disorders and new functions of occludin and TJs.