Mitochondrial DNA and Inflammation Are Associated with Cerebral Vessel Remodeling and Early Diabetic Kidney Disease in Patients with Type 2 Diabetes Mellitus.

Cerebrovascular disease accounts for major neurologic disabilities in patients with type 2 diabetes mellitus (DM). A potential association of mitochondrial DNA (mtDNA) and inflammation with cerebral vessel remodeling in patients with type 2 DM was evaluated. A cohort of 150 patients and 30 healthy controls were assessed concerning urinary albumin/creatinine ratio (UACR), synaptopodin, podocalyxin, kidney injury molecule-1 (KIM-1), N-acetyl-ß-(D)-glucosaminidase (NAG), interleukins IL-17A, IL-18, IL-10, tumor necrosis factor-alpha (TNFα), intercellular adhesion molecule-1 (ICAM-1). MtDNA-CN and nuclear DNA (nDNA) were quantified in peripheral blood and urine by qRT-PCR. Cytochrome b (CYTB) gene, subunit 2 of NADH dehydrogenase (ND2), and beta 2 microglobulin nuclear gene (B2M) were assessed by TaqMan assays. mtDNA-CN was defined as the ratio of the number of mtDNA/nDNA copies, through analysis of the CYTB/B2M and ND2/B2M ratio; cerebral Doppler ultrasound: intima-media thickness (IMT)-the common carotid arteries (CCAs), the pulsatility index (PI) and resistivity index (RI)- the internal carotid arteries (ICAs) and middle cerebral arteries (MCAs), the breath-holding index (BHI). The results showed direct correlations of CCAs-IMT, PI-ICAs, PI-MCAs, RI-ICAs, RI-MCAs with urinary mtDNA, IL-17A, IL-18, TNFα, ICAM-1, UACR, synaptopodin, podocalyxin, KIM-1, NAG, and indirect correlations with serum mtDNA, IL-10. BHI correlated directly with serum IL-10, and serum mtDNA, and negatively with serum IL-17A, serum ICAM-1, and NAG. In neurologically asymptomatic patients with type 2 DM cerebrovascular remodeling and impaired cerebrovascular reactivity may be associated with mtDNA variations and inflammation from the early stages of diabetic kidney disease.

Elderly Individuals Residing in Nursing Homes in Western Romania Who Have Been Diagnosed with Hearing Loss are at a Higher Risk of Experiencing Cognitive Impairment.

Purpose: The objective of this research was to determine if there is any correlation between the severity of neurocognitive disorder and hearing impairment in the elderly. Patients and Methods: This is a population-based observational study that included subjects aged ≥ 65 years. They were evaluated for the existence of cardiovascular risk factors, diabetes, stroke, alcohol abuse, and smoking. Hearing impairment was diagnosed by an audiologist, using behavioral audiometric examination. These evaluations might have been performed in response to concerns about hearing loss, or they could have been a routine component of yearly comprehensive health screenings that included a Mini-Mental State Examination 2nd Edition (MMSE-2) test. According to the results of the MMSE-2 scale, we divided the individuals into two groups, Group I for those who had cognitive impairment and severe neurocognitive disorder, and Group II for those who did not have cognitive impairment. Results: The study enrolled 203 patients with a mean age of 77 ± 7.5 years (range 65-98), 99 (48%) were males. When comparing the two groups, group I patients presented more often cardiovascular risk factors, stroke, diabetes, and impaired hearing. The univariable logistic regression found that cognitive impairment was significantly more frequent in the elderly with cardiovascular disease, diabetes, and stroke (p<0.0001). The multivariate regression analysis found that stroke (p<0.0001) diabetes (p=0.0008), cardiovascular disease (p=0.0004), and impaired hearing (p=0.0011) were significantly linked to cognitive impairment. The occurrence of hearing impairment in the elderly was related to having an MMSE-2 score of 14 or below. Conclusion: According to the findings of this research, the elderly who have trouble hearing in addition to other conditions might have an increased risk for severe neurocognitive disorder.

SARS­CoV­2 infection and associated risk factors for clinical cases of cerebral venous thrombosis: A case series.

The present study focused on examining the association between the SARS-CoV-2 virus, responsible for the COVID-19 pandemic, and cerebral venous thrombosis (CVT), a specific form of stroke that affects the brain's vessels and sinuses. While COVID-19 is primarily recognized for its respiratory impact, it may also affect other organs, including the brain. One notable aspect of COVID-19 is its association with coagulopathy, an abnormal condition of blood clotting. Coagulopathy may result in various complications, including neurological ones such as stroke. The study analyzed data obtained from patients admitted to a neurology department who had confirmed neurological pathologies along with COVID-19. It specifically examined the cases of three patients with neurological conditions and COVID-19, discussing their risk factors and how their conditions progressed clinically. The study concluded that COVID-19 infection increases the likelihood of stroke, particularly within the initial 10 days after infection. CVT in particular is strongly linked to COVID-19 and its underlying mechanisms involve immune systemic processes, cytokine storms, increased blood thickness, thrombogenesis, hypercoagulability and inflammation. The presence of SARS-CoV-2 infection may worsen the procoagulant cascade, thereby affecting the clinical condition of patients with CVT. The study underscores the importance of recognizing this uncommon but treatable consequence of COVID-19 infection. Furthermore, it highlights the uniqueness of the study in evaluating COVID-19 infection in patients with CVT from Romania and South-East Europe. The findings support the existence of neurological disorders, including clotting complications in the brain's sinuses and vessels, in individuals infected with SARS-CoV-2. Several risk factors contribute to the development of CVT, such as infections, oral contraceptives, pregnancy, hematological disorders, trauma, autoimmune disorders and malignancies.

Untargeted Metabolomics by Ultra-High-Performance Liquid Chromatography Coupled with Electrospray Ionization-Quadrupole-Time of Flight-Mass Spectrometry Analysis Identifies a Specific Metabolomic Profile in Patients with Early Chronic Kidney Disease.

Chronic kidney disease (CKD) has emerged as one of the most progressive diseases with increased mortality and morbidity. Metabolomics offers new insights into CKD pathogenesis and the discovery of new biomarkers for the early diagnosis of CKD. The aim of this cross-sectional study was to assess metabolomic profiling of serum and urine samples obtained from CKD patients. Untargeted metabolomics followed by multivariate and univariate analysis of blood and urine samples from 88 patients with CKD, staged by estimated glomerular filtration rate (eGFR), and 20 healthy control subjects was performed using ultra-high-performance liquid chromatography coupled with electrospray ionization-quadrupole-time of flight-mass spectrometry. Serum levels of Oleoyl glycine, alpha-lipoic acid, Propylthiouracil, and L-cysteine correlated directly with eGFR. Negative correlations were observed between serum 5-Hydroxyindoleacetic acid, Phenylalanine, Pyridoxamine, Cysteinyl glycine, Propenoylcarnitine, Uridine, and All-trans retinoic acid levels and eGFR. In urine samples, the majority of molecules were increased in patients with advanced CKD as compared with early CKD patients and controls. Amino acids, antioxidants, uremic toxins, acylcarnitines, and tryptophane metabolites were found in all CKD stages. Their dual variations in serum and urine may explain their impact on both glomerular and tubular structures, even in the early stages of CKD. Patients with CKD display a specific metabolomic profile. Since this paper represents a pilot study, future research is needed to confirm our findings that metabolites can serve as indicators of early CKD.

Diagnosis and Management of Cerebral Venous Thrombosis Due to Polycythemia Vera and Genetic Thrombophilia: Case Report and Literature Review.

(1) Background: Cerebral venous and dural sinus thrombosis (CVT) rarely appears in the adult population. It is difficult to diagnosis because of its variable clinical presentation and the overlapping signal intensities of thrombosis and venous flow on conventional MR images and MR venograms. (2) Case presentation: A 41-year-old male patient presented with an acute isolated intracranial hypertension syndrome. The diagnosis of acute thrombosis of the left lateral sinus (both transverse and sigmoid portions), the torcular Herophili, and the bulb of the left internal jugular vein was established by neuroimaging data from head-computed tomography, magnetic resonance imaging (including Contrast-enhanced 3D T1-MPRAGE sequence), and magnetic resonance venography (2D-TOF MR venography). We detected different risk factors (polycythemia vera-PV with JAK2 V617F mutation and inherited low-risk thrombophilia). He was successfully treated with low-molecular-weight heparin, followed by oral anticoagulation. (3) Conclusions: In the case of our patient, polycythemia vera represented a predisposing risk factor for CVT, and the identification of JAK2 V617F mutation was mandatory for the etiology of the disease. Contrast-enhanced 3D T1-MPRAGE sequence proved superior to 2D-TOF MR venography and to conventional SE MR imaging in the diagnosis of acute intracranial dural sinus thrombosis.

Orphan Drugs in Neurology-A Narrative Review.

BACKGROUND AND AIMS: Orphan diseases, or rare diseases, are defined in Europe as diseases that affect less than 5 out of every 10,000 citizens. Given the small number of cases and the lack of profit potential, pharmaceutical companies have not invested much in the development of possible treatments. However, over the last few years, new therapies for rare diseases have emerged, giving physicians a chance to offer personalized treatment. With this paper, we aim to present some of the orphan neurological diseases for which new drugs have been developed lately. METHODS: We have conducted a literature review of the papers concerning rare diseases and their treatment, and we have analyzed the existing studies for each orphan drug. For this purpose, we have used the Google Scholar search engine and the Orphanet. We have selected the studies published in the last 15 years. RESULTS: Since the formation of the National Organization for Rare Diseases, the Orphan Drug Act, and the National Institutes of Health Office of Rare Diseases, pharmacological companies have made a lot of progress concerning the development of new drugs. Therefore, diseases that until recently were without therapeutic solutions benefit today from personalized treatment. We have detailed in our study over 15 neurological and systemic diseases with neurological implications, for which the last 10-15 years have brought important innovations regarding their treatment. CONCLUSIONS: Many steps have been taken towards the treatment of these patients, and the humanity and professionalism of the pharmaceutical companies, along with the constant support of the patient's associations for rare diseases, have led to the discovery of new treatments and useful future findings.

New Imaging Features of Multinodular and Vacuolating Neuronal Tumor Revealed by Alcohol and Illicit Drugs Consumption.

It has been almost a decade since the multinodular and vacuolating neuronal tumor (MVNT) was first described. In 2021, WHO classified it as a defined entity, and it is considered one of the glioneuronal and neuronal tumors. Due to its similarities with dysembryoplastic neuroepithelial tumors (DNET), some authors consider it a variant of these, ranking in the category of malformations, but genetic alterations favor a neoplastic origin. We present a 29-year-old male with a generalized onset tonic-clonic seizure after a nightclub party. Imaging studies revealed a right temporal multinodular and vacuolating neuronal tumor confirmed by biopsy. It is considered a nonaggressive, "leave me alone" brain lesion, which does not require biopsy because of well-defined MRI characteristics. Surgery is indicated only in symptomatic cases. We consider that this lesion was revealed by his seizure, most probably provoked (with normal video EEG recording) by the consumption of a lot of alcohol, illicit drugs, and sleep loss after a club party. We recommended close monitoring, but our patient preferred the surgery. Our case added more imaging details corroborated with the histopathology features of MVNT. FLAIR images revealed hypointense nodules surrounded by hyperintense peripheral rings and areas of high signal intensity between the nodules, which correspond to the histopathological architecture. To our knowledge, this is the first case of MVNT with diffusion tensor imaging and fiber tractography imaging studies.

Narrative Review of New Insight into the Influence of the COVID-19 Pandemic on Cardiovascular Care.

Background and Objectives: The purpose of this paper was to perform a literature review on the effects of the COVID-19 pandemic on cardiothoracic and vascular surgery care and departments. Materials and Methods: To conduct this evaluation, an electronic search of many databases was conducted, and the resulting papers were chosen and evaluated. Results: Firstly, we have addressed the impact of COVID-19 infection on the cardiovascular system from the pathophysiological and treatment points of view. Afterwards, we analyzed every cardiovascular disease that seemed to appear after a COVID-19 infection, emphasizing the treatment. In addition, we have analyzed the impact of the pandemic on the cardiothoracic and vascular departments in different countries and the transitions that appeared. Finally, we discussed the implications of the cardiothoracic and vascular specialists' and residents' work and studies on the pandemic. Conclusions: The global pandemic caused by SARS-CoV-2 compelled the vascular profession to review the treatment of certain vascular illnesses and find solutions to address the vascular consequences of COVID-19 infection. The collaboration between vascular surgeons, public health specialists, and epidemiologists must continue to investigate the impact of the pandemic and the response to the public health issue.

Long noncoding RNAs may impact podocytes and proximal tubule function through modulating miRNAs expression in Early Diabetic Kidney Disease of Type 2 Diabetes Mellitus patients.

Aims: Long noncoding RNAs (lncRNAs) play key roles in the pathophysiology of DKD involving actions of microRNAs (miRNAs). The aims of the study were to establish the involvement of selected lncRNAs in the epigenetic mechanisms of podocyte damage and tubular injury in DKD of type 2 diabetes mellitus (DM) patients in relation to a particular miRNAs profile. Methods: A total of 136 patients with type 2 DM and 25 healthy subjects were assessed in a cross-sectional study concerning urinary albumin: creatinine ratio (UACR), eGFR, biomarkers of podocyte damage (synaptopodin, podocalyxin) and of proximal tubule (PT) dysfunction (Kidney injury molecule-1-KIM-1, N-acetyl-D-glucosaminidase-NAG), urinary lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), nuclear-enriched abundant transcript 1 (NEAT1), myocardial infarction-associated transcript (MIAT), taurine-upregulated gene 1 (TUG1), urinary miRNA21, 124, 93, 29a. Results: Multivariable regression analysis showed that urinary lncMALAT1 correlated directly with urinary synaptopodin, podocalyxin, KIM-1, NAG, miRNA21, 124, UACR, and negatively with eGFR, miRNA93, 29a (p<0.0001; R2=0.727); urinary lncNEAT1 correlated directly with synaptopodin, KIM-1, NAG, miRNA21, 124, and negatively with eGFR, miRNA93, 29a (p<0.0001; R2=0.702); urinary lncMIAT correlated directly with miRNA93 and 29a, eGFR (p<0.0001; R2=0.671) and negatively with synaptopodin, KIM-1, NAG, UACR, miRNA21, 124 (p<0.0001; R2=0.654); urinary lncTUG1 correlated directly with eGFR, miRNA93, 29a, and negatively with synaptopodin, podocalyxin, NAG, miRNA21, 124 (p<0.0001; R2=0.748). Conclusions: In patients with type 2 DM lncRNAs exert either deleterious or protective functions within glomeruli and PT. LncRNAs may contribute to DKD through modulating miRNAs expression and activities. This observation holds true independently of albuminuria and DKD stage.

New perspectives in the use of laser diode transscleral cyclophotocoagulation. A prospective single center observational cohort study.

PURPOSE: The paper intends to present the results of using new methods of a new generation diode laser transscleral cyclophotocoagulation (TSCPC) in patients with different types of glaucoma. PATIENTS, MATERIALS AND METHODS: There have been treated 53 eyes from 59 patients with glaucoma refractory to medical, laser or surgical treatment. We have used the newest generation of 810 nm wavelength diode laser. There have been used two protocols of continuous-wave diode laser emitting radiation for cyclophotocoagulation. The first technique - the standard cyclophotocoagulation (high power and low exposure duration) - has been used for the eyes with limited visual function [visual acuity (VA) extremely low or eyes disorganized]. The second technique - slow coagulation, also named "slow burn" (lower power and greater exposure duration) - has been used for the eyes with apparently better visual prognosis (VA≥20∕400). For evaluation, we followed both subjective parameters (eye pain decrease) and objective parameters [intraocular pressure (IOP) lowering and VA evolution]. Patients have been evaluated before laser intervention and postoperative at one, three and six months. RESULTS: IOP has significantly decreased in both patient groups. In the eyes with better visual function (VA≥1∕20), where we have used the "slow coagulation" technique, we found no decrease of VA. Eye pain has disappeared in almost all treated cases. CONCLUSIONS: The diode laser TSCPC is an efficient method of lowering IOP and decreasing eye pain. The "slow burn" technique has been shown its efficiency for extending the indications of cyclophotocoagulation also in glaucomatous eyes with better functional prognosis.

Left internal carotid artery agenesis associated with communicating arteries anomalies. A case report.

Agenesis, aplasia and hypoplasia of the internal carotid artery are rare congenital malformations. They are usually asymptomatic and incidentally discovered through ultrasound or imagistic tests. The aim of this study is to improve their management in our Departments. We report here the case of a 39-year-old woman addressed to our ambulatory in 2013 for benign symptoms like dizziness and headache. Imagistic findings (magnetic resonance imaging of the brain, and cervical spine, and magnetic resonance angiography of the head and neck) indicated a very rare condition: left internal carotid artery agenesis accompanied by the absence of the pre-communicant part of the left anterior cerebral artery and of the right posterior communicating artery. Internal carotid artery agenesis is an uncommon congenital anomaly and it could be misdiagnosed as stenosis/occlusion of this artery. This condition is important to be recognized due to the associated hemodynamic changes and in order to discover and evaluate other accompanying vascular malformations (aneurysms, collateral channels) and their life threatening potential risks (subarachnoid hemorrhage or ischemia). Also, it has a special importance in case of planning carotid or trans-sphenoidal hypophyseal surgery.

Femtosecond-LASIK outcomes using the VisuMax®-MEL® 80 platform for mixed astigmatism refractive surgery.

AIM: To evaluate the predictability, efficacy and safety of Femtosecond-laser-assisted in situ keratomileusis (LASIK) procedure for mixed astigmatism. PATIENTS, MATERIALS AND METHODS: We prospectively evaluated for 12 months 74 eyes (52 patients) with mixed astigmatism that underwent Femtosecond-LASIK treatment. The preoperative mean refractive sphere value was +1.879±1.313 diopters (D) and the mean refractive cylinder value was -4.169±1.091 D. The anterior corneal flap was cut using the VisuMax® femtosecond laser and then the stromal ablation was done using the MEL® 80 excimer laser. RESULTS: Mean age was 30.22±6.421 years with 61.53% female patients. Postoperative spherical equivalent at 12 months was within ±0.5D of emmetropia in 75.8% of eyes and within ±1D in 97.3% of eyes. Postoperative uncorrected distance visual acuity was equivalent to or better than the preoperative corrected distance visual acuity in 91.9% of eyes. Compared to the preoperative corrected distance visual acuity (CDVA), 8.1% of eyes gained one line, 2.7% gained two lines and 2.7% gained three lines of visual acuity. CONCLUSIONS: Femtosecond-LASIK using the VisuMax®-MEL® 80 platform appears to have safe, effective and predictable results in mixed astigmatic eyes. The results are impressive for high refractive error treatment and for improvement of both uncorrected and corrected distance visual acuity.

Giant cell arteritis with arteritic anterior ischemic optic neuropathy.

Giant cell arteritis (GCA) is an inflammatory vasculitis of unknown etiology that mainly involves large and medium arteries, particularly the cranial branches of the aorta. GCA with consecutive arteritic-anterior ischemic optic neuropathy (A-AION) has rarely been diagnosed in Romania. Recently, we encountered an 83-year-old patient who presented with left eye visual impairment and corresponding optic disc diffusely swollen and pale. He also had typical manifestations of GCA, such as malaise, and temporal headache, and a highly elevated erythrocyte sedimentation rate and C-reactive protein level. Biopsy of his left superficial temporal artery revealed a granulomatous inflammation with multinucleated giant cell infiltration, so he was diagnosed with GCA with consecutive left A-AION. Because without treatment, this affection usually progresses very rapidly, the patient was promptly treated with an adequate dosage of steroids, which was essential to save the visual function of both eyes. Our case report confirms the potential of visual recovery after prompt corticosteroid treatment in GCA with eye involvement.

Therapy with atorvastatin versus rosuvastatin reduces urinary podocytes, podocyte-associated molecules, and proximal tubule dysfunction biomarkers in patients with type 2 diabetes mellitus: a pilot study.

BACKGROUND: Diabetic nephropathy is a severe complication of Type 2 diabetes. Tubular lesions may play an important role in its early stages. The aim of our study was to determine if atorvastatin protects the podocytes and the proximal tubule in patients with Type 2 diabetes. METHODS: A total of 63 patients with Type 2 diabetes completed this 6-months prospective pilot study. They were randomized to continue rosuvastatin therapy (control group) or to be administered an equipotent dose of atorvastatin (intervention group), and were assessed regarding urinary podocytes, podocyte-associated molecules, and biomarkers of proximal tubule dysfunction. RESULTS: The patients from the intervention group presented a significant reduction in podocyturia (from 7.0 to 4.0 cells/ml, p < .05), urinary nephrin (from 1.7 to 1.3 mg/g, p < .001), urinary vascular endothelial growth factor (from 262.8 to 256.9, p < .01), urinary alpha1-microglobulin (from 10.0 to 8.3 mg/g, p < .01), urinary kidney injury molecule-1 (from 139.5 to 136.3 ng/g, p < .001), and urinary advanced glycation end-products (from 112.6 to 101.3 pg/ml, p < .001). Podocyturia correlated directly with the podocyte damage biomarkers, proximal tubule dysfunction biomarkers, albumin to creatinine ratio, and advanced glycation end-products, and inversely with the glomerular filtration rate. CONCLUSIONS: In patients with Type 2 diabetes, atorvastatin exerts favorable effects on the kidney. There is a correlation between the evolution of the podocytes and of the proximal tubule biomarkers, supporting the hypothesis that the glomerular changes parallel proximal tubule dysfunction in the early stages of diabetic nephropathy.

An evaluation on multidisciplinary management of carotid body paragangliomas: a report of seven cases.

Carotid body paragangliomas (CBPGLs) are a rare neoplasms of the neuroendocrine system that affect the carotid glomus. The aim of this study is to improve their management in our Departments. This retrospective analysis reports family history, clinical presentation, imaging diagnostics, Shamblin classification, surgical treatment, complications, and the outcome of seven patients with CBPGLs. All lesions were represented by a painless cervical mass, with no functional or bilateral neck tumors. One patient had two different localizations (the second one was a glomus tumor of the right prelachrymal sac), and a family history for CBPGL. All neck tumors were diagnosed during duplex ultrasound corroborated by magnetic resonance imaging (MRI), and by magnetic resonance angiography (MR-A). They presented a diameter between 3 and 5 cm (MRI). Complete subadventitial resection of the tumor was performed in all patients, with no preoperative embolization in any of the cases. The CBPGLs were confirmed on histopathology and immunohistochemistry. Lymph node metastasis was not found in any of the cases. Mortality and perioperative stroke rates were null. Transitory cranial nerve deficit occurred in one case without permanent palsy. After a follow-up of three years in each patient, there were no signs of tumor recurrence in any of the cases. Relatively early diagnosis of CBPGL was possible in our seven patients using multidisciplinary management. Preoperative planning of the surgical procedure by integrated diagnostic imaging was essential in our study to operate only Shamblin group II tumors, minimizing the known risk of complications associated with large CBPGL (group III).

Clinical and color Doppler imaging features of one patient with occult giant cell arteritis presenting arteritic anterior ischemic optic neuropathy.

Anterior ischemic optic neuropathies (AIONs) represent a segmental infarction of the optic nerve head (ONH) supplied by the posterior ciliary arteries (PCAs). Blood supply blockage can occur with or without arterial inflammation. For this reason, there are two types of AIONs: non-arteritic (NA-AION), and arteritic (A-AION), the latter is almost invariably due to giant cell arteritis (GCA). GCA is a primary vasculitis that predominantly affects extracranial medium-sized arteries, particularly the branches of the external carotid arteries (including superficial temporal arteries - TAs). One patient with clinical suspicion of acute left AION was examined at admission following a complex protocol including color Doppler imaging (CDI) of orbital vessels, and color duplex sonography of the TAs and of the carotid arteries. She presented an equivocal combination of an abrupt, painless, and severe vision loss in the left eye, and an atypical diffuse hyperemic left optic disc edema. She had characteristic CDI features for GCA with eye involvement: high resistance index, with absent, or severe diminished blood flow velocities, especially end-diastolic velocities, in all orbital vessels, especially on the left side (A-AION). Typical sonographic feature in temporal arteritis as part of GCA was "dark halo" sign. On the other hand, she did not present classic clinical or systemic symptoms of GCA: temporal headache, tender TAs, malaise (occult GCA). The left TA biopsy confirmed the diagnosis of GCA. The ultrasound investigations enabled prompt differentiation between NA-AION and A-AION, the later requiring in her case immediate steroid treatment, to prevent further visual loss in the right eye.

Glycated peptides are associated with the variability of endothelial dysfunction in the cerebral vessels and the kidney in type 2 diabetes mellitus patients: a cross-sectional study.

BACKGROUND: Diabetic atherosclerosis and microangiopathy parallel diabetic nephropathy. The aim of our study was to evaluate the pattern of endothelial dysfunction in two vascular territories, the kidney and the brain, both affected by diabetic vasculopathic complications. The endothelial variability was evaluated in relation to advanced glycation end-products modified peptides. METHODS: Seventy patients with type 2 diabetes mellitus and 11 healthy subjects were assessed concerning urine albumin: creatinine ratio, plasma and urinary advanced glycation end-products, plasma asymmetric dimethyl-arginine, serum cystatin C, intima-media thickness in the common carotid arteries, the pulsatility index, the resistance index in the internal carotid arteries and the middle cerebral arteries, the cerebrovascular reactivity through the breath-holding test. RESULTS: The breath-holding index correlated with asymmetric dimethyl-arginine (R²=0.151; p<0.001), plasma advanced glycation end-products (R²=0.173; p<0.001), C-reactive protein (R²=0.587; p<0.001), duration of diabetes mellitus (R²=0.146; p=0.001), cystatin C (R²=0.220; p<0.001), estimated glomerular filtration rate (R²=0.237; p=0.001). Urine albumin: creatinine ratio correlated with urinary advanced glycation end-products (R²=0.257; p<0.001), but not with asymmetric dimethyl-arginine (R²=0.029; p=0.147). CONCLUSIONS: In type 2 diabetic patients endothelial dysfunction in the cerebral vessels appears to be dissociated from glomerular endothelial dysfunction in early diabetic nephropathy. Advanced glycation end-products could impact both the cerebral vessels and the glomerular endothelium.