Byproducts of normal mitochondrial metabolism and homeostasis include the buildup of potentially damaging levels of reactive oxygen species (ROS), Ca2+, etc., which must be normalized. Evidence suggests that brief mitochondrial permeability transition pore (mPTP) openings play an important physiological role maintaining healthy mitochondria homeostasis. Adaptive and maladaptive responses to redox stress may involve mitochondrial channels such as mPTP and inner membrane anion channel (IMAC). Their activation causes intra- and intermitochondrial redox-environment changes leading to ROS release. This regenerative cycle of mitochondrial ROS formation and release was named ROS-induced ROS release (RIRR). Brief, reversible mPTP opening-associated ROS release apparently constitutes an adaptive housekeeping function by the timely release from mitochondria of accumulated potentially toxic levels of ROS (and Ca2+). At higher ROS levels, longer mPTP openings may release a ROS burst leading to destruction of mitochondria, and if propagated from mitochondrion to mitochondrion, of the cell itself. The destructive function of RIRR may serve a physiological role by removal of unwanted cells or damaged mitochondria, or cause the pathological elimination of vital and essential mitochondria and cells. The adaptive release of sufficient ROS into the vicinity of mitochondria may also activate local pools of redox-sensitive enzymes involved in protective signaling pathways that limit ischemic damage to mitochondria and cells in that area. Maladaptive mPTP- or IMAC-related RIRR may also be playing a role in aging. Because the mechanism of mitochondrial RIRR highlights the central role of mitochondria-formed ROS, we discuss all of the known ROS-producing sites (shown in vitro) and their relevance to the mitochondrial ROS production in vivo.

Mitochondrial Reactive Oxygen Species (ROS) and ROS-Induced ROS Release

Photoacoustic (PA) imaging, also called optoacoustic imaging, is a new biomedical imaging modality based on the use of laser-generated ultrasound that has emerged over the last decade. It is a hybrid modality, combining the high-contrast and spectroscopic-based specificity of optical imaging with the high spatial resolution of ultrasound imaging. In essence, a PA image can be regarded as an ultrasound image in which the contrast depends not on the mechanical and elastic properties of the tissue, but its optical properties, specifically optical absorption. As a consequence, it offers greater specificity than conventional ultrasound imaging with the ability to detect haemoglobin, lipids, water and other light-absorbing chomophores, but with greater penetration depth than purely optical imaging modalities that rely on ballistic photons. As well as visualizing anatomical structures such as the microvasculature, it can also provide functional information in the form of blood oxygenation, blood flow and temperature. All of this can be achieved over a wide range of length scales from micrometres to centimetres with scalable spatial resolution. These attributes lend PA imaging to a wide variety of applications in clinical medicine, preclinical research and basic biology for studying cancer, cardiovascular disease, abnormalities of the microcirculation and other conditions. With the emergence of a variety of truly compelling in vivo images obtained by a number of groups around the world in the last 2–3 years, the technique has come of age and the promise of PA imaging is now beginning to be realized. Recent highlights include the demonstration of whole-body small-animal imaging, the first demonstrations of molecular imaging, the introduction of new microscopy modes and the first steps towards clinical breast imaging being taken as well as a myriad of in vivo preclinical imaging studies. In this article, the underlying physical principles of the technique, its practical implementation, and a range of clinical and preclinical applications are reviewed.

/pdf/biomedical-photoacoustic-imaging-4s982wv96j.pdf

Biomedical photoacoustic imaging

https://aasldpubs.onlinelibrary.wiley.com/doi/epdf/10.1002/hep.28156

AASLD guidelines for treatment of chronic hepatitis B

MAFLD: A Consensus-Driven Proposed Nomenclature for Metabolic Associated Fatty Liver Disease.

https://www.journal-of-hepatology.eu/article/S0168-8278(15)00259-7/pdf

EASL-ALEH Clinical Practice Guidelines: Non-invasive tests for evaluation of liver disease severity and prognosis.

https://www.ajkd.org/article/S0272-6386(11)00537-3/pdf

Tenofovir-associated kidney toxicity in HIV-infected patients: a review of the evidence.

Objectives The aims of the study were to describe the clinical presentation and renal and bone abnormalities in a case series of HIV-infected patients receiving treatment with tenofovir (TDF), and to recommend appropriate screening for toxicity related to TDF. Methods Patients were identified from referrals to a specialist HIV renal clinic. Patients were included if treatment with TDF was assessed as the primary cause of the renal function impairment and clinical data were available prior to and following discontinuation of TDF treatment. Data were collected from case note review and clinic databases. Results

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1468-1293.2009.00716.x

Tenofovir-associated renal and bone toxicity

Spectroscopic photoacoustic imaging has the potential to discriminate between normal and lipid-rich atheromatous areas of arterial tissue by exploiting the differences in the absorption spectra of lipids and normal arterial tissue in the 740 to 1400 nm wavelength range. Identification of regions of high lipid concentration would be useful to identify plaques that are likely to rupture (vulnerable plaques). To demonstrate the feasibility of visualizing lipid-rich plaques, samples of human aortas were imaged in forward mode, at wavelengths of 970 and 1210 nm. It was shown that the structure of the arterial wall and the boundaries of lipid-rich plaques obtained from the photoacoustic images were in good agreement with histology. The presence of lipids was also confirmed by comparing the photoacoustic spectra (740 to 1400 nm) obtained in a region within the plaque to the spectral signature of lipids. Furthermore, a lipid-rich plaque was successfully imaged while illuminating the sample through 2.8 mm of blood demonstrating the possibility of implementing the photoacoustic technique in vivo.

https://www.spiedigitallibrary.org/journals/Journal-of-Biomedical-Optics/volume-17/issue-6/061209/Spectroscopic-photoacoustic-imaging-of-lipid-rich-plaques-in-the-human/10.1117/1.JBO.17.6.061209.pdf

Spectroscopic photoacoustic imaging of lipid-rich plaques in the human aorta in the 740 to 1400 nm wavelength range.

https://www.kidney-international.org/article/S0085-2538(15)55699-8/pdf

In vivo multiphoton imaging of mitochondrial structure and function during acute kidney injury

A number of therapeutic drugs are toxic to the kidney proximal tubule (PT) and can cause the renal Fanconi syndrome (FS). The most frequently implicated drugs are cisplatin, ifosfamide, tenofovir, sodium valproate and aminoglycoside antibiotics, and the new oral iron chelator deferasirox has also recently been associated with FS. The incidence of full or partial FS is almost certainly under-estimated due to a lack of appropriate systematic studies, variations in definitions of tubular dysfunction and under-reporting of adverse events. The clinical features of FS are amino aciduria, low molecular weight proteinuria, hypophosphataemia, metabolic acidosis and glycosuria. The most serious complications are bone demineralization from urinary phosphate wasting and progressive decline in kidney function. Commonly used tests for kidney function such as estimated glomerular filtration rate and urine albumin/creatinine ratio are not sensitive markers of PT toxicity; patients at risk should thus be monitored with more appropriate tests, and drugs should be stopped or reduced in dose if toxicity occurs. Substantial recovery of PT function can occur after withdrawal of therapy, but this can take months and chronic damage may persist in some cases.

https://www.zora.uzh.ch/id/eprint/105858/1/hct258.pdf

Andrew M. Hall

Papers

Tenofovir-associated kidney toxicity in HIV-infected patients: a review of the evidence.

Tenofovir-associated renal and bone toxicity

Spectroscopic photoacoustic imaging of lipid-rich plaques in the human aorta in the 740 to 1400 nm wavelength range.

In vivo multiphoton imaging of mitochondrial structure and function during acute kidney injury

Drug-induced renal Fanconi syndrome