Blood Exchange Research Articles

Rift Valley fever virus is able to cross the human blood-brain barrier in vitro by direct infection with no deleterious effects.

Rift Valley fever (RVF) is a zoonotic arboviral disease that causes recurrent epidemics in Africa that may trigger fatal neurological disorders. However, the mechanisms of neuroinvasion by which the RVF virus (RVFV) reaches the human central nervous system (CNS) remain poorly characterized. In particular, it is not clear how RVFV is able to cross the human blood-brain barrier (hBBB), which is a neurovascular endothelium that protects the brain by regulating brain and blood exchanges. To explore these mechanisms, we used an in vitro hBBB model to mimic in vivo hBBB selectiveness and apicobasal polarity. Our results highlight the ability of RVFV to cross the hBBB by direct infection in a non-structural protein S (NSs)-independent but strain-dependent manner, leading to astrocyte and pericyte infections. Interestingly, RVFV infection did not induce hBBB disruption and was associated with progressive elimination of infected cells with no impairment of the tight junction protein scaffold and barrier function. Our work also shows that NSs, a well described RVFV virulence factor, limited the establishment of the hBBB-induced innate immune response and subsequent lymphocyte recruitment. These results provide in vitro confirmation of the ability of RVFV to reach human CNS by direct infection of the hBBB without altering its barrier function, and provide new directions to explore human RVFV neurovirulence and neuroinvasion mechanisms.IMPORTANCEThe RVF virus (RVFV) is capable of infecting humans and inducing severe and fatal neurological disorders. Neuropathogenesis and human central nervous system (CNS) invasion mechanisms of RVFV are still unknown, with only historical studies of autopsy data from fatal human cases in the 1980s and exploration studies in rodent models. One of the gaps in understanding RVFV human pathogenesis is how RVFV is able to cross the blood-brain barrier (BBB) in order to reach the human CNS. For the first time, we show that RVFV is able to directly infect cells of the human BBB in vitro to release viral particles into the human CNS, a well-characterized neuroinvasion mechanism of pathogens. Furthermore, we demonstrate strain-dependent variability of this neuroinvasion mechanism, identifying possible viral properties that could be explored to prevent neurological disorders during RVFV outbreaks.

Biological impact of manual blood exchange in malignant Bordetella pertussis infection in infants.

Manual blood exchange (MBE) is a leukoreduction therapy for hyperleukocytosis in Bordetella spp. We describe the impact of BE on clinical and biological parameters in critically ill children with malignant pertussis. This is a monocentric retrospective review of patients with malignant pertussis infection treated with MBE. It describes the evolution of haemodynamic, ventilatory, haematologic and metabolic characteristics before and after MBE. Between January 2006 and December 2021, nine patients (median age 43 days, range: 13-80 days) had 16 MBE for malignant pertussis. All patients were mechanically ventilated, and 7/9 patients developed pulmonary hypertension during their paediatric intensive care unit (PICU) stay. Overall, 3/9 patients survived, and the mean PICU length of stay was 8.5 days (range: 1-52 days). We found a significant reduction of the leukocyte count (pre-MBE: 61.8 G/L [interquartile range (IQR): 55.8-74.8] vs. post-MBE: 19.4 G/L [IQR: 17.7-24.1]; p ≤ 0.001) and significant oxygenation improvement (pre-MBE SpO2/FiO2: 190 [IQR: 106-200] vs. post-MBE SpO2/FiO2: 242 [IQR: 149-250]; p = 0.03). The main side effects were a significant reduction of thrombocytes (pre-MBE: 411 G/L [IQR: 166.5-563.5] vs. post-MBE: 66 G/L [IQR: 46-82.5]; p = <0.001) and of ionized calcium (iCa) (pre-MBE iCa: 1.3 [IQR: 1.22-1.37] vs. post-MBE iCa: 1.25 [IQR: 1.85-2.24]; p = 0.03). MBE efficiently reduces leukocytes and improves oxygenation in severe Bordetella pertussis infection in infants. Careful monitoring of calcium and thrombocytes seems mandatory.

Ophthalmic acid is a bloodborne metabolite that contributes to age-induced cardiomyocyte hypertrophy.

Cardiac aging involves the development of left ventricular hypertrophy alongside a decline in functional capacity. Here, we use neutral blood exchange to demonstrate that the acute removal of age-accumulated blood factors significantly regresses cardiac hypertrophy in aged mice. The reversal of hypertrophy was not attributed to age-associated hemodynamic effects, implicating a role of blood-derived factors. In addition, the overarching paradigm of systemic aging maintains that the age-related overabundance of plasma proteins are largely responsible for causing pathological phenotypes in tissues. Our results suggest that blood metabolites, not proteins, drive cardiac hypertrophy instead. Upon analyzing serum metabolomics data sets, we identified ophthalmic acid as a circulating metabolite whose levels increase with advanced age. Treatment of adult mouse and neonatal rat cardiomyocytes in culture with ophthalmic acid increased their relative surface areas. This study uncovers a non-protein metabolite that may contribute to cardiomyocyte hypertrophy during aging. Identifying a method to counteract ophthalmic acid's hypertrophic effects may reveal novel therapeutic opportunities for cardiac rejuvenation.

Blood-based therapies to combat neurodegenerative diseases.

Neurodegeneration, known as the progressive loss of neurons in terms of their structure and function, is the principal pathophysiological change found in the majority of brain-related disorders. Ageing has been considered the most well-established risk factor in most common neurodegenerative diseases, such as Parkinson's disease (PD) and Alzheimer's disease (AD). There is currently no effective treatment or cure for these diseases; the approved therapeutic options to date are only for palliative care. Ageing and neurodegenerative diseases are closely intertwined; reversing the aspects of brain ageing could theoretically mitigate age-related neurodegeneration. Ever since the regenerative properties of young blood on aged tissues came to light, substantial efforts have been focused on identifying and characterizing the circulating factors in the young and old systemic milieu that may attenuate or accentuate brain ageing and neurodegeneration. Later studies discovered the superiority of old plasma dilution in tissue rejuvenation, which is achieved through a molecular reset of the systemic proteome. These findings supported the use of therapeutic blood exchange for the treatment of degenerative diseases in older individuals. The first objective of this article is to explore the rejuvenating properties of blood-based therapies in the ageing brains and their therapeutic effects on AD. Then, we also look into the clinical applications, various limitations, and challenges associated with blood-based therapies for AD patients.

Continuous blood exchange in rats as a novel approach for experimental investigation

Blood exchange therapy, specifically Whole blood exchange (WBE), is increasingly being utilized in clinical settings to effectively treat a range of diseases. Consequently, there is an urgent requirement to establish convenient and clinically applicable animal models that can facilitate the exploration of blood exchange therapy mechanisms. Our study conducted continuous WBE in rats through femoral and tail vein catheterization using dual-directional syringe pumps. To demonstrate the applicability of continuous WBE, drug-induced hemolytic anemia (DIHA) was induced through phenylhydrazine hydrochloride (PHZ) injection. Notability, the rats of DIHA + WBE group all survived and recovered within the subsequent period. After the implementation of continuous WBE therapy day (Day 1), the DIHA + WBE group exhibited a statistically significant increase in red blood cells (RBC) (P = 0.0343) and hemoglobin (HGB) levels (P = 0.0090) compared to DIHA group. The rats in the DIHA + WBE group exhibited a faster recovery rate compared to the DIHA group, indicating the successful establishment of a continuous blood exchange protocol. This experimental approach demonstrates not just promising efficacy in the treatment of DIHA and offers a valuable tool for investigating the underlying mechanisms of blood exchange. Furthermore, it has a great potential to the advancement of biomedical research such as drug delivery exploration.

Neonatal and Obstetrical Outcomes of Pregnancies Complicated by Alloimmunization.

Despite advances in the prevention of rhesus (Rh)(D) alloimmunization, alloantibodies to Rh(D) and non-Rh(D) red blood cell antigens continue to be detected in ∼4% of US pregnancies and can result in hemolytic disease of the fetus and newborn (HDFN). Recent reports on HDFN lack granularity and are unable to provide antibody-specific outcomes. The objective of this study was to calculate the frequency of alloimmunization in our large hospital system and summarize the outcomes based on antibody specificity, titer, and other clinical factors. We identified all births in a 6-year period after a positive red blood cell antibody screen result during pregnancy and summarized their characteristics and outcomes. A total of 707 neonates were born after a positive maternal antibody screen result (3.0/1000 live births). In 31 (4%), the positive screen result was due to rhesus immune globulin alone. Of the 676 neonates exposed to alloantibodies, the direct antibody test (DAT) result was positive, showing antigen-positivity and evidence of HDFN in 37% of those tested. Neonatal disease was most severe with DAT-positive anti-Rh antibodies (c, C, D, e, E). All neonatal red blood cell transfusions (15) and exchange transfusions (6) were due to anti-Rh alloimmunization. No neonates born to mothers with anti-M, anti-S, anti-Duffy, anti-Kidd A, or anti-Lewis required NICU admission for hyperbilirubinemia or transfusion. Alloimmunization to Rh-group antibodies continues to cause a majority of the severe HDFN cases in our hospital system. In neonates born to alloimmunized mothers, a positive DAT result revealing antigen-positivity is the best predictor of anemia and hyperbilirubinemia.

Leukemia circulation kinetics revealed through blood exchange method

Leukemias and their bone marrow microenvironments undergo dynamic changes over the course of disease. However, little is known about the circulation kinetics of leukemia cells, nor the impact of specific factors on the clearance of circulating leukemia cells (CLCs) from the blood. To gain a basic understanding of CLC dynamics over the course of disease progression and therapeutic response, we apply a blood exchange method to mouse models of acute leukemia. We find that CLCs circulate in the blood for 1–2 orders of magnitude longer than solid tumor circulating tumor cells. We further observe that: (i) leukemia presence in the marrow can limit the clearance of CLCs in a model of acute lymphocytic leukemia (ALL), and (ii) CLCs in a model of relapsed acute myeloid leukemia (AML) can clear faster than their untreated counterparts. Our approach can also directly quantify the impact of microenvironmental factors on CLC clearance properties. For example, data from two leukemia models suggest that E-selectin, a vascular adhesion molecule, alters CLC clearance. Our research highlights that clearance rates of CLCs can vary in response to tumor and treatment status and provides a strategy for identifying basic processes and factors that govern the kinetics of circulating cells.

The Blood Brotherhood and Colonial Treaties and Alliances: Between Myth and Reality

Abstract This article examines the representation and use of the blood exchange between European expeditionary leaders, that worked in the service of king Leopold II, and African rulers in Central and East Africa during the late nineteenth century. While the blood brotherhood played a role in the appeasement of African rulers and the conclusion of treaties, the details and origins of the procedure are often unclear. Europeans believed that the blood brotherhood was an African legal custom, even though recent anthropological studies suggest it differed from the inter-African version of the blood brotherhood. Europeans styled the blood brotherhood as the African counterpart to the European treaty, which served to support the legality of the much-contested treaties that Leopold II’s representatives had concluded, often under dubious circumstances. While the blood brotherhood therefore functioned as a practical tool to establish European influence and sovereignty over African rulers, it was also as a means of glorifying the white European explorer as a pseudo-scientist and well-meaning broker of peace. This article complicates the traditional narrative of how treaties were concluded during the Scramble for Africa and highlights the need for a critical re-examination of the legal practices and representations of colonialism.

Educational Program on Nurses Knowledge about Blood Exchange Transfusion in Neonatal Care Units

Background: Exchange transfusion entails the sequential drawing and injecting of blood aliquots via peripheral or central venous and arterial lines. Notably, arterial lines—either peripheral or umbilical—should not be used for donor blood injections; rather, they should only be used for baby blood withdrawal. To ascertain the Nurses' Knowledge of Blood Exchange Transfusion in Neonatal Intensive Care Units Educational Program. Methods: Designing a quasi-experimental using (non-probability) To ascertain the impact of a training program on nurses' performance with regard to blood exchange transfusion, purposeful sampling was used. The "Statistical Package for Social Science (SPSS) software for Windows (Version 26)" is used to analyze data. Results: This result showed that 33.3%(10) of the study's nurses and 33.3%(10) of the control group's nurses were between the ages of 31 and 35.The study's findings regarding the gender of the nursing staff showed that 53.3% of the participants (19) were female. and of the fifteen participants, 63.3% were men. 50% of the participants are nurses.had a Nursing Institute (15) In terms of general years of experience, 33.3% (10) of the sample had six to ten years of experience, and 3.0% worked in the pediatric department. Conclusion: The study concluded that the nurses’ knowledge about the blood transfusion process before giving the educational program to the patients was poor, and through the intervention and giving the nursing program, their knowledge became good. The reason is due to the effectiveness of the effective programs.

Local Dialogues Between the Endocrine and Exocrine Cells in the Pancreas.

For many years, it has been taught in medical textbooks that the endocrine and exocrine parts of the pancreas have separate blood supplies that do not mix. Therefore, they have been studied by different scientific communities, and patients with pancreatic disorders are treated by physicians in different medical disciplines, endocrinologists and gastroenterologists, respectively. The conventional model that every islet in each pancreatic lobule receives a dedicated arterial blood supply was first proposed in 1932 and it has been inherited to date. Recently, in vivo intravital recording of red blood cell flow in mouse islets as well as in situ structural analysis of 3D pancreatic vasculature from hundreds of islets provided evidence for preferentially integrated pancreatic blood flow in 6 mammalian species. The majority of islets have no association with the arteriole and there is bidirectional blood exchange between the two segments. Such vascularization may allow an entire downstream region of islets and acinar cells to be simultaneously exposed to a topologically and temporally specific plasma content, which could underlie an adaptive sensory function as well as common pathogeneses of both portions of the organ in pancreatic diseases including diabetes.

Effect of HHFNC therapy on organ oxygenation and brain metabolism in neonates receiving exchange transfusion.

Exchange transfusion therapy is a complex and invasive procedure with a high risk coefficient. This method involves replacing the entire blood of a child with fresh blood with double circulating blood volume in a short period, typically in 1-2 h. This procedure can cause the body's internal environment to be unstable, which can put newborns under a lot of stress. This stress can lead to many, including abnormal laboratory biochemical examination, low or high blood pressure, and apnea. There is also the possibility of secondary infection and, in severe cases, cardiac arrest. This study investigated the effects of Humidified high-flow nasal cannula (HHFNC) ventilation on hemodynamic stability and oxygenation during exchange transfusion in neonates. Furthermore, the effects on brain metabolism and salivary cortisol during exchange transfusion were also analyzed. In this study, the control group consisted of 45 cases of children who underwent simple blood exchange between 1 May 2017, and 31 December 2019 control group. The observation group consisted of 33 cases of children who underwent blood exchange under HHFNC support between 1 January 2020, and 30 April 2022. The study compared various physiological parameters between the control and the observation group. These included blood gas analysis, pulmonary artery pressure, ejection fraction, invasive mean arterial pressure, heart rate, cerebral oxygenation, intestinal oxygenation, renal oxygenation, and duration of blood exchange. Furthermore, the study also compared the changes in brain metabolic and salivary cortisol indicators between the two groups of children. The results did not reveal any significant difference in PH, PaO2, and duration of blood exchange between the control and the observation group. However, the observation group's invasive mean arterial pressure, ejection fraction, cerebral oxygenation, intestinal oxygenation, and renal oxygenation were higher than those of the control group. Furthermore, compared with the control group, the pulmonary artery pressure, heart rate, and PaCO2 were lower in the observation group. There was a statistically significant difference between the two groups of children in the relevant clinical indicators (total bilirubin, hemoglobin, SPO2, etc.) after exchange transfusion. After 1 h of blood exchange and after blood exchange, the salivary cortisol levels of the observation group were lower than the control group. The difference was statistically significant. The NAA/Cho and Cho/Cr values of the two groups of children were also significantly different. During blood exchange, unstable hemodynamics substantially impact organ oxygenation. The results of this study suggest that HHFNC and specific ventilation pressure support can improve the respiratory rate and help maintain blood flow stability and organ oxygenation. This technique can also reduce adverse reactions caused by blood exchange, minimizing patient stress and reducing the impact on brain metabolism.

Improving Nurses' Performance Regarding Care of Neonates with Hyperbilirubinemia Undergoing Blood Exchange: An Educational Program

Improving Nurses' Performance Regarding Care of Neonates with Hyperbilirubinemia Undergoing Blood Exchange: An Educational Program

Placental vessel segmentation and registration in fetoscopy: Literature review and MICCAI FetReg2021 challenge findings

Fetoscopy laser photocoagulation is a widely adopted procedure for treating Twin-to-Twin Transfusion Syndrome (TTTS). The procedure involves photocoagulation pathological anastomoses to restore a physiological blood exchange among twins. The procedure is particularly challenging, from the surgeon’s side, due to the limited field of view, poor manoeuvrability of the fetoscope, poor visibility due to amniotic fluid turbidity, and variability in illumination. These challenges may lead to increased surgery time and incomplete ablation of pathological anastomoses, resulting in persistent TTTS. Computer-assisted intervention (CAI) can provide TTTS surgeons with decision support and context awareness by identifying key structures in the scene and expanding the fetoscopic field of view through video mosaicking. Research in this domain has been hampered by the lack of high-quality data to design, develop and test CAI algorithms. Through the Fetoscopic Placental Vessel Segmentation and Registration (FetReg2021) challenge, which was organized as part of the MICCAI2021 Endoscopic Vision (EndoVis) challenge, we released the first large-scale multi-center TTTS dataset for the development of generalized and robust semantic segmentation and video mosaicking algorithms with a focus on creating drift-free mosaics from long duration fetoscopy videos. For this challenge, we released a dataset of 2060 images, pixel-annotated for vessels, tool, fetus and background classes, from 18 in-vivo TTTS fetoscopy procedures and 18 short video clips of an average length of 411 frames for developing placental scene segmentation and frame registration for mosaicking techniques. Seven teams participated in this challenge and their model performance was assessed on an unseen test dataset of 658 pixel-annotated images from 6 fetoscopic procedures and 6 short clips. For the segmentation task, overall baseline performed was the top performing (aggregated mIoU of 0.6763) and was the best on the vessel class (mIoU of 0.5817) while team RREB was the best on the tool (mIoU of 0.6335) and fetus (mIoU of 0.5178) classes. For the registration task, overall the baseline performed better than team SANO with an overall mean 5-frame SSIM of 0.9348. Qualitatively, it was observed that team SANO performed better in planar scenarios, while baseline was better in non-planner scenarios. The detailed analysis showed that no single team outperformed on all 6 test fetoscopic videos. The challenge provided an opportunity to create generalized solutions for fetoscopic scene understanding and mosaicking. In this paper, we present the findings of the FetReg2021 challenge, alongside reporting a detailed literature review for CAI in TTTS fetoscopy. Through this challenge, its analysis and the release of multi-center fetoscopic data, we provide a benchmark for future research in this field.

A Patient with Target Cells and Hyperkalemia - or why Hematologists Should Still be Able to ‘Fly by Sight‘

INTRODUCTION: Hematology has changed. Both benign and malignant hematology rely heavily on new diagnostic techniques, such as flow-cytometry, cytogenetics and most recently single gene analysis by next generation sequencing. Examination of a blood smear has come out of favor and is usually performed by lab technicians and not by the hematologist. This case report describes how examination of the blood smear which showed an unexpected red blood cell morphology eventually led after 40 years to the right diagnosis. CASE: R. C. is a 42-year-old male (100 kg = 220 lbs, 1,83 m = 6 ft, BMI 29,9) diagnosed in childhood with spherocytosis. His medical history was remarkable for that after birth he needed blood exchange for kernicterus (bilirubin-induced brain dysfunction), and since age 3 months he had epileptic seizures. His blood counts were not that abnormal and since he had no or only mild anemia throughout his whole life he received no further w/u for his blood disorder. Another remarkable finding was that he always had hyperkalemia but since he had no symptoms (no palpitations, dyspnea, chest pain, nausea, or vomiting) and nobody found an explanation no further workup was pursued. In November 2022 he presented to a nearby hospital for epileptic seizures. His spleen was mildly enlarged (14,5 x 6,7 cm) and because of his h/o spherocytosis the neurologist sent him for hematologic re-evaluation. His physical was unremarkable except for that the margin of the spleen was palpable. He was neither pale nor icteric. He drinks no alcohol and does not smoke. Medications were lamotrigen, cholecalciferol, and cenobamate. His blood counts are shown in the table. Since his MCHC was normal, which does not fit spherocytosis, we ordered a blood smear shown in the figure. There were no spherocytes but many target cells. Then we sent for an eosin-5′-maleimide (EMA) binding test which was also unremarkable (124% binding, with spherocytosis usually &amp;lt; 80%). However, acidified glycerol lysis test showed increased osmotic fragility (lysis time 45 sec., normal &amp;gt; 1800 sec). This unusual combination together with his hyperkalemia led to the hypothesis of a disorder related to the xerocytosis or stomatocytosis complex. However, the morphologic picture did not fit stomatocytosis. We therefore sent for NGS analysis which revealed a heterozygous mutation of SLC2A1, variant c.857G&amp;gt;A; p.Gly286Asp (stomatin-deficient cryohydrocytosis). Stomatin-deficient cryohydrocytosis is a very rare congenital deficiency in GLUT1 and stomatin with moderate hemolytic anemia, pseudohyperkalemia and various neurologic defects. The occurrence of target cells (but no stomatocytes) with cryohydrocytosis has - to our knowledge - been reported only once before. CONCLUSIONS: In Germany benign hematology no longer plays the role it had 30-40 years ago. This may be due to the fact that congenital anemias and erythrocyte abnormalities occur less frequently in the relatively homogeneous German population, at least less often than in southeastern Europe or in other countries. Also, patients with mild stable anemia that do not require treatment, are often not seen by a hematologist. To the authors' opinion the most relevant change is that blood smear examination, which is reimbursed with 50 cents has fallen out of fashion in daily practice. However, in this case only the blood smear revealed, that the prior diagnosis of spherocytosis could not be correct. There were no spherocytes but target cells. The patient, though, had not the typical factors associated with target cells (no liver disease, no hyperlipidemia, no thalassemia or iron deficiency). Eventually NGS analysis revealed stomatin-deficient cryohydrocytosis. We present this case because it was the blood smear examination that eventually led to the right diagnosis. All hematologists should have a microscope “next door” and even if blood smear examination is reimbursed poorly it is a diagnostic tool still at the core of our profession

Pulmonary hypertension in sickle cell disease

Sickle cell disease (SCD) is a complex genetic disorder that has long challenged both patients and healthcare professionals. One of its chronic and debilitating complications is pulmonary hypertension (PH). SCD-associated PH is often post-capillary, secondary to left heart disease. It can also sometimes be pre-capillary with multiple and often interrelated mechanisms including obstructive remodeling of the pulmonary vascular bed secondary to hemolysis, endothelial dysfunction, thrombosis, hypoxia, or associated risk factors like portal hypertension. Screening symptomatic patients with echocardiographic signs of PH is crucial to determine those who should undergo right heart catheterization, the cornerstone exam to diagnose and categorize patients with PH. The workup following the diagnosis relies on identifying the cause of PH to personalize treatment. Ongoing efforts are made to treat this complex condition, starting with treating the underlying disease with hydroxyurea or chronic blood exchange transfusion. Robust data on the efficacy of PAH-specific therapies are lacking in this specific population. Initiation of such therapies must be made by an expert center after a case-by-case assessment of the benefit-risk ratio according to the phenotype and the mechanisms involved in the development of PH. Efforts are also poured into studying the interventional and medical therapies used on chronic thromboembolic PH for patients presenting with a thrombotic form. The management of those patients requires a multidisciplinary approach, with conjoint efforts from PH and SCD specialists.

The Computed Sinusoid

Hepatic sinusoids are lined with thin endothelial cells with transcellular pores, termed fenestrations. These fenestrations are open channels that connect the sinusoidal lumen to the underlying Space of Disse (SoD) and the hepatocytes of the liver parenchyma. Fenestrations range from 0.05 to 0.35 µm in diameter and cover 5–15% of the sinusoidal endothelial surface area, depending on their location along the sinusoids. The direct measurement of hemodynamic parameters, such as pressure and flow velocity, remains challenging within the narrow sinusoids. Such knowledge would increase our understanding of the physiology of the hepatic niche and possible implications in aging or diseases in which fenestrations are reduced or lost. Few simulations of liver blood flow focus on the level of the individual sinusoid, and fewer still include the transcellular pores (fenestrations) of the sinusoidal endothelium. Furthermore, none have included (i) a porosity gradient along the sinusoid wall, modeled using through-all pores rather than a porous medium, (ii) the presence of the SoD, or (iii) lymphatic drainage. Herein, computed fluid dynamics (CFD) simulations were performed using a numerical model with relevant anatomical characteristics (length, diameter, porosity, inlet/outlet pressure, and lymphatic outflow from the portal region of the SoD). The greatest contribution to luminal velocity magnitude and pressure was the overall shape of the vessel. Divergent-radius models yielded velocity magnitudes 1.5–2 times higher than constant-radius models, and pressures were 5–8% lower in the divergent-radius models compared to the constant-radius models. Porosity only modestly contributed to luminal pressure. The luminal velocity magnitude was largely unaffected by the presence or absence of lymphatic drainage. Velocity magnitudes through fenestrations were lower in higher-porosity models (20%) vs. lower-porosity models (5%) across all models (0.4–0.55-fold lower). Velocity magnitudes through the space of Disse were increased 3–4 times via the addition of lymphatic drainage to the models, while pressures were decreased by 6–12%. The flow velocity in the SoD was modified via differences in porosity, while the flow velocity in the lumens of the sinusoids was largely unaffected. The overall shape of the vessel is the single most important factor in the pressure flow behavior of the sinusoidal lumen. The flow rate over hepatocytes and the SoD is modestly affected by the distribution of porosity along the sinusoid and greatly affected by the lymphatic drainage, parameters that would be of interest for modeling the exchange of blood with the hepatic parenchyma.

In-situ Gels for Brain Delivery: Breaching the Barriers.

The blood-brain barrier (BBB) regulates blood and chemical exchange in the central nervous system. It is made up of brain parenchyma capillary endothelial cells. It separates the interstitial cerebrospinal fluid from the circulation and limits brain drug entry. Peptides, antibodies, and even tiny hydrophilic biomolecules cannot flow across the BBB due to their semi-permeability. It protects the brain from poisons, chemicals, and pathogens, and blood cells penetrate brain tissue. BBB-facilitated carrier molecules allow selective permeability of nutrients such as D-glucose, L-lactic acid, L-phenylalanine, L-arginine, and hormones, especially steroid hormones. Brain barriers prevent drug molecules from entering, making medication delivery difficult. Drugs can reach specific brain regions through the nasal cavity, making it a preferred route. The in-situ gels are mucoadhesive, which extends their stay in the nasal cavity, allows them to penetrate deep and makes them a dependable way of transporting numerous medications, including peptides and proteins, straight into the central nervous system. This approach holds great potential for neurological therapy as they deliver drugs directly to the central nervous system, with less interference and better drug release control. The brain affects daily life by processing sensory stimuli, controlling movement and behaviour, and sustaining mental, emotional, and cognitive functioning. Unlike systemic routes, the nasal mucosa is extensively vascularized and directly contacts olfactory sensory neurons. Compared to the systemic circulation, this improves brain bioavailability of medications. Drugs can be delivered to the brain using in-situ gel formulations safely and efficiently, with a greater therapeutic impact than with traditional techniques.

Hematopoietic aging: Cellular, molecular, and related mechanisms.

Aging is accompanied by significant inhibition of hematopoietic and immune system function and disruption of bone marrow structure. Aging-related alterations in the inflammatory response, immunity, and stem cell niches are at the root of hematopoietic aging. Understanding the molecular mechanisms underlying hematopoietic and bone marrow aging can aid the clinical treatment of aging-related diseases. In particular, it is unknown how the niche reprograms hematopoietic stem cells (HSCs) in an age-dependent manner to maintain normal hematopoiesis in elderly individuals. Recently, specific inhibitors and blood exchange methods have been shown to reshape the hematopoietic niche and reverse hematopoietic aging. Here, we present the latest scientific discoveries related to hematopoietic aging and hematopoietic system rejuvenation, discuss the relationships between hematopoietic niche aging and HSC aging, and describe related studies on stem cell-mediated regulation of hematopoietic aging, aiming to provide new ideas for further study.

Impact of Metabolic Stress on BeWo Syncytiotrophoblast Function.

During placental formation, cytotrophoblasts (CTBs) fuse into multinucleate, microvilli-coated syncytiotrophoblasts (STBs), which contact maternal blood, mediating nutrient, metabolite, and gas exchange between mother and fetus, and providing a barrier against fetal infection. Trophoblasts remodel the surrounding extracellular matrix through the secretion of matrix metalloproteinases (MMPs). Maternal obesity and diabetes mellitus can negatively impact fetal development and may impair trophoblast function. We sought to model the impact of metabolic stress on STB function by examining MMP and hormone secretion. The BeWo CTB cell line was syncytialized to STB-like cells with forskolin. Cell morphology was examined by electron microscopy and immunofluorescence; phenotype was further assessed by ELISA and RT-qPCR. STBs were exposed to a metabolic stress cocktail (MetaC: 30 mM glucose, 10 nM insulin, and 0.1 mM palmitic acid). BeWo syncytialization was demonstrated by increased secretion of HCGβ and progesterone, elevated syncytin gene expression (ERVW-1 and ERVFRD-1), loss of tight junctions, and increased surface microvilli. MetaC strongly suppressed syncytin gene expression (ERVW-1 and ERVFRD-1), suppressed HCGβ and progesterone secretion, and altered both MMP-9 and MMP-2 production. Metabolic stress modeling diabetes and obesity altered BeWo STB hormone and MMP production in vitro.

Off with the blues: Therapeutic plasma exchange in a case of copper sulphate poisoning

CuSO4 (Copper sulphate) poisoning though rare, is associated with high mortality. It involves multiple organ systems and if not dealt with promptly can lead to death. Supportive care and chelation therapy along with TPE (therapeutic plasma exchange), whole blood exchange or red cell exchange can be employed in management. We report such a case where swift clinical improvement was seen after TPE.