Melatonin Improves Mitochondrial Dynamics and Function in the Kidney of Zücker Diabetic Fatty Rats.

Obesity and associated diabetes (diabesity) impair kidney mitochondrial dynamics by augmenting fission and diminishing fusion, which results in mitochondrial and renal dysfunction. Based on available evidence, the antioxidant activities of melatonin may improve impaired renal mitochondrial function in obese diabetic animals by restoring the imbalanced dynamics through inhibiting fission and promoting fusion. Male Zücker diabetic fatty (ZDF) rats and lean littermates (ZL) were orally treated either with melatonin (10 mg/kg BW/day) (M-ZDF and M-ZL) or vehicle (C-ZDF and C-ZL) for 17 weeks. Kidney function was evaluated by measurement of total urine volume, proteinuria, creatinine clearance, and assessment of kidney mitochondrial dynamics and function. C-ZDF exhibited impaired dynamics and function of kidney mitochondria in comparison to C-ZL. Melatonin improved nephropathy of ZDF rats and modulated their mitochondrial dynamics by reducing expression of Drp1 fission marker and increasing that of fusion markers, Mfn2 and Opa1. Furthermore, melatonin ameliorated mitochondrial dysfunction by increasing respiratory control index and electron transfer chain complex IV activity. In addition, it lowered mitochondrial oxidative status. Our findings show that melatonin supplementation improves nephropathy likely via modulation of the mitochondrial fission/fusion balance and function in ZDF rats.

Cortical Contrast Processing in Retinitis Pigmentosa: Evidence of PVEPs Spatial Functions.

OBJECTIVE: To study the effect of check width size of the stimuli on the amplitude and latency of the P100 component of visual evoked potentials recorded in patients with retinitis pigmentosa (RP). METHODS: Pattern reversal visual evoked potentials (PVEPs) were recorded in 16 RP patients and 20 visually normal subjects. Pattern reversal stimuli with five different check widths and 100% of contrast were projected in the right eye of both patients and control subjects. PVEPs induced by stimuli with 78%, 16%, and 6% of contrast were also recorded in 10 of the control subjects. RESULTS: In RP patients, the amplitude of P100 was smaller than controls in all check sized used and the peak P100 amplitude was obtained with a larger check width than in controls. P100 was also delayed in RP patients in all check sizes studied. The P100 amplitude- and latency-check size functions of RP patients were like those found in control subjects with low contrast stimuli of 16% and 6%. CONCLUSION: The PVEPs spatial functions of RP patients show quantitative and qualitative changes, suggesting disease induced alteration in the neural processing of stimulus contrast.

Atypical antipsychotics produce within-session decrements on self-stimulation of the rat medial prefrontal cortex.

It has been described that "typical" antipsychotic drugs (APDs) induce characteristic within-session response decrements in operant behaviors, including intracranial self-stimulation (ICSS). In contrast, recent reports have shown that in food operant behavior, clozapine and a number of "atypical" APDs do not give rise to within-session effects. However, to elucidate whether or not this is a common property of atypical APDs, their effects on other operant models need to be studied. To address this question we investigated the temporal pattern of ICSS responding, after systemic administration of five atypical APDs and the typical antipsychotic, haloperidol. Rats were trained to lever press for electrical stimulation at the medial prefrontal cortex (mPFC), and response rates were recorded during each 3-min period of the 15-min session. Significant within-session response decrements on mPFC ICSS were observed with haloperidol, risperidone, sertindole and olanzapine but not with clozapine or ziprasidone. The magnitude of within-session decline produced by the APDs tested was positively correlated with their affinity for dopamine D2 receptors. The results show for the first time that atypical APDs are capable to induce within-session decrements on ICSS behavior, and suggest that this particular temporal pattern of responding is not exclusively characteristic of typical APDs. The results are also consistent with the hypothesis that the ability of APDs to induce greater within-session effects may be related, in part, to potent D2 antagonism.

Multifocal ERG Guiding Therapy in a Case of Hydroxychloroquine Premaculopathy.

We report the case of a 28-year-old female treated for systemic lupus erythematosus with hydroxychloroquine (200 mg/day) for 11 years. She was visually asymptomatic, with normal fundus appearance, normal colour vision testing findings, 20/20 visual acuity in both eyes, and only mild central bilateral defects on 10-2 perimetry. Multifocal electroretinography (mfERG) showed low density values for ring 1 in both eyes. Because the patient had not previously responded to alternative treatments and in consultation with her physician, the hydroxychloroquine dose was reduced to 200 mg four days/week. Four serial mfERGs performed at 4, 18, 25, and 34 months after dose reduction showed a progressive improvement in the definition and density of the responses until they were normalized at the third mfERG (25 months after hydroxychloroquine dose reduction). The fourth and final mfERG at 34 months confirmed the recovery in both eyes. Perimetry defects were mostly normalized. These results demonstrate the importance of mfERG for the safe management of patients under long-term hydroxychloroquine treatment.

Ocular toxicity and functional vision recovery in a patient treated with hydroxychloroquine.

CASE REPORT: We report the case of a 64-year-old woman with rheumatoid arthritis and Sjögren's syndrome, treated during 48 months with hydroxychloroquine that was removed after an ophthalmological evaluation showed bilateral vision loss associated with paracentral scotoma in the visual field, fundoscopic macular pigmentary changes, and severely impaired central multifocal electrorretinogram (mfERG). Twelve months after treatment withdrawal, visual acuity and central mfERG had surprisingly improved. This is an unusual case of functional recovery after treatment withdrawal. We consider that central mfERG is a more sensitive test than pattern electrorretinogram in the detection of retinal toxicity and functional vision recovery after hydroxychloroquine treatment cessation.

Rapid onset of Wernicke's encephalopathy following gastric restrictive surgery.

A patient with severe vomiting following gastric banding developed Wernicke's encephalopathy. All neurological disorders disappeared with thiamine treatment. This complication may be prevented by keen awareness, early diagnosis and treatment, in patients with persistent vomiting. Vitamin and mineral supplementation must be taken in patients following bariatric surgery.

Mesencephalic area measured by transcranial sonography in the differential diagnosis of parkinsonism.

BACKGROUND: Transcranial B-mode sonography (TCS) has become an important tool in the differential diagnosis of parkinsonism given that current technology enables an adequate assessment of brain structures. In this study we aimed at evaluating the usefulness of midbrain area measured by TCS in the differential diagnosis between Parkinson's Disease (PD) and Progressive Supranuclear Palsy (PSP). METHODS: Patients with a diagnosis of PD or PSP according to current clinical criteria were recruited. PSP patients were classified as Richardson's syndrome and PSP-parkinsonism. TCS was performed and the mesencephalic area and third ventricle width were measured offline by an examiner blinded to clinical diagnosis. RESULTS: TCS was performed in 60 patients (75% PD, 25% PSP). Eight patients (13,3%) had inadequate acoustic window. Patients with PSP had a smaller mesencephalic area (3.58 cm(2) vs 5.28 cm(2), p < 0.001). A mesencephalic area ≥4.27 cm(2) discriminates PD from PSP with a positive predictive value 100%. Patients with PSP also had a higher third ventricle diameter (8.84 mm vs 5.11 mm, p < 0.001). Within the PSP group patients with Richardson's syndrome had a wider third ventricle than patients with PSP-Parkinsonism phenotype (9.57 mm vs 7 mm, p = 0.01), but no differences were found in the mesencephalic area between both phenotypes. CONCLUSIONS: Measurement of the mesencephalic area and the third ventricle width by TCS is a non-invasive, easily accessible technique that is useful in the differential diagnosis between PD and PSP, at least in the late stages of the disease.

Maculopathy in patient with systemic lupus erythematosus treated with hydroxychloroquine.

A 50-years-old woman with systemic lupus erythematosus treated for 13 years with hydroxychloroquine developed nephropathy and high blood pressure five years ago as well as moderate loss of vision in her right eye. Fundoscopy showed alterations of macular pigmentation only in the right eye. Visual fields 10-2 were normal in both eyes. Optical coherence tomography showed hyperreflective foveal thickening with a hyporreflective cavity underlying in the right macula, and was normal in left macula. Fluorescein angiography showed no bulls-eye pattern, but did show microaneurysms in vascular arcades. Multifocal central electroretinogram was diminished in right eye and the electrorretinogram pattern was diminished in both eyes. We concluded that the alterations of the right eye were suggestive of ischemic maculopathy, not hydroxychloroquine toxicity.

A new basal sauropod dinosaur from the middle Jurassic of Niger and the early evolution of sauropoda.

BACKGROUND: The early evolution of sauropod dinosaurs is poorly understood because of a highly incomplete fossil record. New discoveries of Early and Middle Jurassic sauropods have a great potential to lead to a better understanding of early sauropod evolution and to reevaluate the patterns of sauropod diversification. PRINCIPAL FINDINGS: A new sauropod from the Middle Jurassic of Niger, Spinophorosaurus nigerensis n. gen. et sp., is the most complete basal sauropod currently known. The taxon shares many anatomical characters with Middle Jurassic East Asian sauropods, while it is strongly dissimilar to Lower and Middle Jurassic South American and Indian forms. A possible explanation for this pattern is a separation of Laurasian and South Gondwanan Middle Jurassic sauropod faunas by geographic barriers. Integration of phylogenetic analyses and paleogeographic data reveals congruence between early sauropod evolution and hypotheses about Jurassic paleoclimate and phytogeography. CONCLUSIONS: Spinophorosaurus demonstrates that many putatively derived characters of Middle Jurassic East Asian sauropods are plesiomorphic for eusauropods, while South Gondwanan eusauropods may represent a specialized line. The anatomy of Spinophorosaurus indicates that key innovations in Jurassic sauropod evolution might have taken place in North Africa, an area close to the equator with summer-wet climate at that time. Jurassic climatic zones and phytogeography possibly controlled early sauropod diversification.

Adherence to aspirin in secondary prevention of ischemic stroke.

OBJECTIVE: Compliance with antiplatelet therapy is essential for the efficiency of secondary prevention of ischemic stroke. The objective of this study was to evaluate adherence to aspirin treatment in patients with ischemic stroke. PATIENTS AND METHODS: We studied outpatients of 5 neurological ambulatory centers in an urban city, Valencia, all with a history of ischemic stroke who had received aspirin for at least 6 months. A personal interview was carried out in all cases, during which the patients were questioned about adherence to treatment. Platelet thromboxane A2 synthesis was assessed in a single laboratory for the biochemical determination in all patients. RESULTS: A total of 73 patients (mean age 67) were studied, with a mean duration of aspirin therapy of 25.4 months (range 6-144 months). Sixty-six patients (90.4%) were included in laboratory tests. All showed inhibition of thromboxane A2 synthesis, consistent with adherence to treatment. CONCLUSIONS: Aspirin compliance was found to be excellent. All the patients who presented themselves for laboratory tests were taking aspirin. Even if the patients who failed to show up for laboratory testing are regarded as noncompliants, at least 90% of all patients were compliants--in agreement with the findings of the recent literature. Personal interview plus biochemical determination of platelet thromboxane A2 synthesis seem adequate for assessing adherence to aspirin.