Efficacy of the Once-Daily Tacrolimus Formulation LCPT Compared to the Immediate-Release Formulation in Preventing Early Post-Transplant Diabetes in High-Risk Kidney Transplant Patients: A Randomized, Controlled, Open-Label Pilot Study (EUDRACT: 2017-000718-52).

: Post-transplant diabetes mellitus (PTDM) and prediabetes (PreDM) are common after renal transplantation and increase the risk of cardiovascular events and mortality. Compared to immediate-release tacrolimus (IR-Tac), the LCPT formulation, with delayed absorption, offers higher bioavailability and a smoother time-concentration curve, potentially reducing beta-cell stress. : This randomized pilot trial compared de novo immunosuppression with IR-Tac (twice daily) and LCPT (once daily).

Real-time imaging of mitochondrial redox reveals increased mitochondrial oxidative stress associated with amyloid β aggregates in vivo in a mouse model of Alzheimer's disease.

Background: Reactive oxidative stress is a critical player in the amyloid beta (Aβ) toxicity that contributes to neurodegeneration in Alzheimer's disease (AD). Damaged mitochondria are one of the main sources of reactive oxygen species and accumulate in Aβ plaque-associated dystrophic neurites in the AD brain. Although Aβ causes neuronal mitochondria reactive oxidative stress in vitro, this has never been directly observed in vivo in the living mouse brain.

Near-infrared fluorescence lifetime imaging of amyloid-β aggregates and tau fibrils through the intact skull of mice.

Non-invasive methods for the in vivo detection of hallmarks of Alzheimer's disease can facilitate the study of the progression of the disease in mouse models and may enable its earlier diagnosis in humans. Here we show that the zwitterionic heptamethine fluorophore ZW800-1C, which has peak excitation and emission wavelengths in the near-infrared optical window, binds in vivo and at high contrast to amyloid-β deposits and to neurofibrillary tangles, and allows for the microscopic imaging of amyloid-β and tau aggregates through the intact skull of mice. In transgenic mouse models of Alzheimer's disease, we compare the performance of ZW800-1C with that of the two spectrally similar heptamethine fluorophores ZW800-1A and indocyanine green, and show that ZW800-1C undergoes a longer fluorescence-lifetime shift when bound to amyloid-β and tau aggregates than when circulating in blood vessels.

Low Incidence of Acute Antibody-Mediated Rejection after HLA Desensitization in Living Donor Kidney Transplant Recipients.

Desensitization allows the performance of human leukocyte antigen (HLA)-incompatible transplants. However, the incidence of acute rejection (AR) is high. This study aims to analyze the incidence of AR after transplantation with HLA-incompatible living donors in patients who underwent desensitization.

Amyloid Beta Oligomers-Induced Ca Entry Pathways: Role of Neuronal Networks, NMDA Receptors and Amyloid Channel Formation.

The molecular basis of amyloid toxicity in Alzheimer's disease (AD) remains controversial. Amyloid β (Aβ) oligomers promote Ca influx, mitochondrial Ca overload and apoptosis in hippocampal neurons in vivo and in vitro, but the primary Ca entry pathways are unclear. We studied Ca entry pathways induced by Aβ oligomers in rat hippocampal and cerebellar neurons.

Bioavailability of once-daily tacrolimus formulations used in clinical practice in the management of De Novo kidney transplant recipients: the better study.

Multicenter, prospective, observational study to compare the relative bioavailability of once-daily tacrolimus formulations in de novo kidney transplant recipients. De novo kidney transplant recipients who started a tacrolimus-based regimen were included 14 days post-transplant and followed up for 6 months. Data from 218 participants were evaluated: 129 in the LCPT group (Envarsus) and 89 in the PR-Tac (Advagraf) group.

Edema Associated With Everolimus de Novo.

Background: The appearance of edema limits the use of everolimus de novo together with tacrolimus and steroids in kidney transplantation. We aimed to investigate the frequency and characteristics of patients with edema and compare them according to the type of immunosuppression.

Methods: We studied 150 kidney transplant recipients between 2015 and 2017 based on receiving everolimus de novo (group A) or mycophenolic acid derivatives (group B).

Isoagglutinin Titers in ABO-Incompatible Kidney Transplant.

Background: A decrease in the isoagglutinin titer <1:8 is usually required for ABO-incompatible (ABOi) transplantation and the presence of high predesensitization titers may condition future transplantation. The aim of the study was to analyze the prognosis of ABOi patients undergoing desensitization and to compare the results according to the baseline isoagglutinin titer.

Methods: ABOi patients transplanted in our center after desensitization with rituximab, apheresis (plasmapheresis, immunoadsorption with Glycosorb, or both) and immunoglobulins were studied.

Mitochondria-ER contacts and glucose: the powerhouse of Alzheimer's disease?

A mechanism involving endoplasmic reticulum-mitochondria contacts noted in diabetes mellitus may explain the neurodegeneration and amyloidogenesis observed in these patients. Urolithin A, a metabolite found in the gut microbiome, is proposed as a therapeutic strategy for the treatment of the diabetes-related dementia.

Toll-like receptors in neuroinflammation, neurodegeneration, and alcohol-induced brain damage.

Toll-like receptors (TLRs) or pattern recognition receptors respond to pathogen-associated molecular patterns (PAMPs) or internal damage-associated molecular patterns (DAMPs). TLRs are integral membrane proteins with both extracellular leucine-rich and cytoplasmic domains that initiate downstream signaling through kinases by activating transcription factors like AP-1 and NF-κB, which lead to the release of various inflammatory cytokines and immune modulators. In the central nervous system, different TLRs are expressed mainly in microglia and astroglial cells, although some TLRs are also expressed in oligodendroglia and neurons.

In vivo brain imaging of mitochondrial Ca in neurodegenerative diseases with multiphoton microscopy.

Mitochondria are involved in a large number of essential roles related to neuronal function. Ca handling by mitochondria is critical for many of these functions, including energy production and cellular fate. Conversely, mitochondrial Ca mishandling has been related to a variety of neurodegenerative diseases.

Therapeutic Strategies to Target Calcium Dysregulation in Alzheimer's Disease.

Alzheimer's disease (AD) is the most common form of dementia, affecting millions of people worldwide. Unfortunately, none of the current treatments are effective at improving cognitive function in AD patients and, therefore, there is an urgent need for the development of new therapies that target the early cause(s) of AD. Intracellular calcium (Ca) regulation is critical for proper cellular and neuronal function.

Mitochondria and Calcium in Alzheimer's Disease: From Cell Signaling to Neuronal Cell Death.

Mitochondrial dysfunction has been implicated in the pathogenesis of almost all neurological diseases, including Alzheimer's disease (AD). Historically, a primary focus in this context has been the link between mitochondrial dynamics and amyloid β toxicity. Recent evidence suggests that dysregulation of mitochondrial calcium homeostasis is also related to tau and other risk factors in AD, although an ongoing challenge in the field is that data collected from different models or experimental settings have not always been consistent.

Role of Toll Like Receptor 4 in Alzheimer's Disease.

Long-term evidence has confirmed the involvement of an inflammatory component in neurodegenerative disorders including Alzheimer's disease (AD). This view is supported, in part, by data suggesting that selected non-steroidal anti-inflammatory drugs (NSAIDs) provide protection. Additionally, molecular players of the innate immune system have recently been proposed to contribute to these diseases.

High mitochondrial calcium levels precede neuronal death in Alzheimer's disease.

Alzheimer's disease (AD), the most common cause of dementia, affects millions of people worldwide. Suggested mechanisms of neurotoxicity in AD include impaired calcium (Ca) homeostasis and mitochondrial dysfunction, both contributing to neuronal damage. Little was known about the exact mitochondrial Ca homeostasis in the living brain, particularly in AD.

Increased mitochondrial calcium levels associated with neuronal death in a mouse model of Alzheimer's disease.

Mitochondria contribute to shape intraneuronal Ca signals. Excessive Ca taken up by mitochondria could lead to cell death. Amyloid beta (Aβ) causes cytosolic Ca overload, but the effects of Aβ on mitochondrial Ca levels in Alzheimer's disease (AD) remain unclear.

Remodeling of Intracellular Ca Homeostasis in Rat Hippocampal Neurons Aged In Vitro.

Aging is often associated with a cognitive decline and a susceptibility to neuronal damage. It is also the most important risk factor for neurodegenerative disorders, particularly Alzheimer's disease (AD). AD is related to an excess of neurotoxic oligomers of amyloid β peptide (Aβo); however, the molecular mechanisms are still highly controversial.

Vasomotion as a Driving Force for Paravascular Clearance in the Awake Mouse Brain.

Paravascular drainage of solutes, including β-amyloid (Aβ), appears to be an important process in brain health and diseases such as Alzheimer's disease (AD) and cerebral amyloid angiopathy (CAA). However, the major driving force for clearance remains largely unknown. Here we used in vivo two-photon microscopy in awake head-fixed mice to assess the role of spontaneous vasomotion in paravascular clearance.

In vivo detection of tau fibrils and amyloid β aggregates with luminescent conjugated oligothiophenes and multiphoton microscopy.

The detection of amyloid beta deposits and neurofibrillary tangles, both hallmarks of Alzheimer's disease (AD), is key to understanding the mechanisms underlying these pathologies. Luminescent conjugated oligothiophenes (LCOs) enable fluorescence imaging of these protein aggregates. Using LCOs and multiphoton microscopy, individual tangles and amyloid beta deposits were labeled in vivo and imaged longitudinally in a mouse model of tauopathy and cerebral amyloidosis, respectively.

Frequency-dependent exacerbation of Alzheimer's disease neuropathophysiology.

Neuronal activity patterns are disrupted in neurodegenerative disorders, including Alzheimer's disease (AD). One example is disruption of corticothalamic slow oscillations responsible for sleep-dependent memory consolidation. Slow waves are periodic oscillations in neuronal activity occurring at frequencies of <1 Hz.

ABO-incompatible living-donor kidney transplantation: Study of 48 patients after desensitisation.

Background: ABO-incompatible living-donor kidney transplantation was regarded as an absolute contraindication. However, it has been carried out for years with good outcomes.

Objective: Our aim was to show the results obtained with this technique in our hospital.

Amyloid β Oligomers Increase ER-Mitochondria Ca Cross Talk in Young Hippocampal Neurons and Exacerbate Aging-Induced Intracellular Ca Remodeling.

Alzheimer's disease (AD) is the most common neurodegenerative disorder and strongly associated to aging. AD has been related to excess of neurotoxic oligomers of amyloid β peptide (Aβo), loss of intracellular Ca homeostasis and mitochondrial damage. However, the intimate mechanisms underlying the pathology remain obscure.

A flow cytometry-based assay reveals that formation of apolipoprotein E (ApoE)-amyloid beta complexes depends on ApoE isoform and cell type.

Apolipoprotein E (ApoE) is a secreted apolipoprotein with three isoforms, E2, E3, and E4, that binds to lipids and facilitates their transport in the extracellular environment of the brain and the periphery. The E4 allele is a major genetic risk factor for the sporadic form of Alzheimer's disease (AD), and studies of human brain and mouse models have revealed that E4 significantly exacerbates the deposition of amyloid beta (Aβ). It has been suggested that this deposition could be attributed to the formation of soluble ApoE isoform-specific ApoE-Aβ complexes.