Is bladder outlet obstruction rat model to induce overactive bladder (OAB) has similarity to human OAB? Research on the events in smooth muscle, collagen, interstitial cell and telocyte distribution.

BACKGROUND: Cellular and cytoskeletal events of overactive bladder (OAB) have not been sufficiently explored in human bladder due to different limitations. Bladder outlet obstruction (BOO) had been induced in different animal models with different methods to induce (OAB). Similarity of the animal models of BOO to the human OAB is postulated but has not been confirmed. The interstitial cells of Cajal (ICCs), and telocytes (TCs) are an important players in smooth muscles conductivity, they had not been well investigated in the previous BOO models. Objectives are to investigate the morphological pattern of cellular, cytoskeleton and telocytes distribution in BOO rat model and to match the events in two time periods and compare it to the findings in real-world human OAB. METHODS: Female Sprague-Dawley rats (Rattus norvegicus) were randomly divided into: sham (n = 10), BOO 6 W (n = 10), BOO 8 W (n = 10). Operative procedure to Induce BOO was done under anesthesia with intraperitoneal Ketamine administration. The Effect of induction of BOO was evaluated after 6 and 8 weeks. The rats were anesthetized, and the urinary bladder was removed, while the rat was unconscious under anaesthesia it was transferred to the inhalation anaesthesia cage for euthanasia, rats were sacrificed under light anesthesia using isoflurane. Care of animals, surgical procedure, and euthanasia adhered to Guide for the Care and Use of Laboratory Animals, and AVMA Guidelines for the Euthanasia of Animals. The retrieved bladder was processed for examination with histopathology, immunohistochemistry (IHC), and transmission electron microscopy (EM). RESULTS: Histological examination of the bladder shows thinner urothelium, condensation of collagen between muscle bundles. IHC with c-kit shows the excess distribution of ICCs between smooth muscle bundles. EM shows frequent distribution of TCs that were situated between collagen fibers. Finings in BOO 6 W group and BOO 8 W group were comparable. CONCLUSION: The animal model study demonstrated increased collagen/ smooth muscle ratio, high intensity of ICCs and presence of TCs. Findings show that a minimally invasive procedure to induce BOO in rats had resulted in an OAB that has morphological changes that were stable in 6 & 8 weeks. We demonstrated the distribution of TCs and ICCs in the rat animal model and defined them. The population of TCs in the BOO rat model is described for the first time, suggests that the TCs and ICCs may contribute to the pathophysiology of OAB. Similarity of animal model to human events OAB was demonstrated. These findings warrant further study to define the role of TCs in OAB. CLINICAL TRIAL REGISTRY: The study does not require a clinical trial registration; it is an experimental animal study in basic science and does not include human subjects.

Real-time monitoring of mitochondrial oxygenation during machine perfusion using resonance Raman spectroscopy predicts organ function.

Organ transplantation is a life-saving procedure affecting over 100,000 people on the transplant waitlist. Ischemia reperfusion injury (IRI) is a major challenge in the field as it can cause post-transplantation complications and limit the use of organs from extended criteria donors. Machine perfusion technology has the potential to mitigate IRI; however, it currently fails to achieve its full potential due to a lack of highly sensitive and specific assays to assess organ quality during perfusion. We developed a real-time and non-invasive method of assessing organs during perfusion based on mitochondrial function and injury using resonance Raman spectroscopy. It uses a 441 nm laser and a high-resolution spectrometer to quantify the oxidation state of mitochondrial cytochromes during perfusion. This index of mitochondrial oxidation, or 3RMR, was used to understand differences in mitochondrial recovery of cold ischemic rodent livers during machine perfusion at normothermic temperatures with an acellular versus cellular perfusate. Measurement of the mitochondrial oxidation revealed that there was no difference in 3RMR of fresh livers as a function of normothermic perfusion when comparing acellular versus cellular-based perfusates. However, following 24 h of static cold storage, 3RMR returned to baseline faster with a cellular-based perfusate, yet 3RMR progressively increased during perfusion, indicating injury may develop over time. Thus, this study emphasizes the need for further refinement of a reoxygenation strategy during normothermic machine perfusion that considers cold ischemia durations, gradual recovery/rewarming, and risk of hemolysis.

Capacity for the management of kidney failure in the International Society of Nephrology Africa region: report from the 2023 ISN Global Kidney Atlas (ISN-GKHA).

The burden of chronic kidney disease and associated risk of kidney failure are increasing in Africa. The management of people with chronic kidney disease is fraught with numerous challenges because of limitations in health systems and infrastructures for care delivery. From the third iteration of the International Society of Nephrology Global Kidney Health Atlas, we describe the status of kidney care in the ISN Africa region using the World Health Organization building blocks for health systems. We identified limited government health spending, which in turn led to increased out-of-pocket costs for people with kidney disease at the point of service delivery. The health care workforce across Africa was suboptimal and further challenged by the exodus of trained health care workers out of the continent. Medical products, technologies, and services for the management of people with nondialysis chronic kidney disease and for kidney replacement therapy were scarce due to limitations in health infrastructure, which was inequitably distributed. There were few kidney registries and advocacy groups championing kidney disease management in Africa compared with the rest of the world. Strategies for ensuring improved kidney care in Africa include focusing on chronic kidney disease prevention and early detection, improving the effectiveness of the available health care workforce (e.g., multidisciplinary teams, task substitution, and telemedicine), augmenting kidney care financing, providing quality, up-to-date health information data, and improving the accessibility, affordability, and delivery of quality treatment (kidney replacement therapy or conservative kidney management) for all people living with kidney failure.

Real-time monitoring of mitochondrial oxygenation during machine perfusion using resonance Raman spectroscopy predicts organ function.

Organ transplantation is a life-saving procedure affecting over 100,000 people on the transplant waitlist. Ischemia reperfusion injury is a major challenge in the field as it can cause post-transplantation complications and limits the use of organs from extended criteria donors. Machine perfusion technology is used to repair organs before transplant, however, currently fails to achieve its full potential due to a lack of highly sensitive and specific assays to predict organ quality during perfusion. We developed a real-time and non-invasive method of assessing organ function and injury based on mitochondrial oxygenation using resonance Raman spectroscopy. It uses a 441 nm laser and a high-resolution spectrometer to predict the oxidation state of mitochondrial cytochromes during perfusion, which vary due to differences in storage compositions and perfusate compositions. This index of mitochondrial oxidation, or 3RMR, was found to predict organ health based on clinically utilized markers of perfusion quality, tissue metabolism, and organ injury. It also revealed differences in oxygenation with perfusates that may or may not be supplemented with packed red blood cells as oxygen carriers. This study emphasizes the need for further refinement of a reoxygenation strategy during machine perfusion that is based on a gradual recovery from storage. Thus, we present a novel platform that provides a real-time and quantitative assessment of mitochondrial health during machine perfusion of livers, which is easy to translate to the clinic.