Cast Formation Research Articles

A histomorphometric study to evaluate the therapeutic effects of biosynthesized silver nanoparticles on the kidneys infected with Plasmodium chabaudi.

The study aimed to verify the pathogenic malarial kidney infections and histopathological pictures in mice infected with Plasmodium chabaudi using Indigofera oblongifolia leaf extract silver nanoparticles (IOLEAgNPs). Fifty healthy adult female mice C57BL/6 were used. Animals were divided into five groups, with each group of ten mice. The first control non-infected group was given distilled water for 7 days. The second group was orally given 50 mg/kg of IOLEAgNPs. The third, fourth, and fifth groups were injected intraperitoneally with 105 parasitized erythrocytes of P. chabaudi. After 1 h, the fourth group received 50 mg/kg of IOLEAgNPs, while the fifth group orally received 10 mg/kg chloroquine phosphate. The histopathology of the kidney was studied by routine histology method with hematoxylin-eosin staining. The kidney revealed cerebral microvessel congestion, hemorrhages, and necrosis. Cast formation, glomerulonephritis, tubular necrosis, and congestion were observed in the kidney cortex. Consequently, the targeted medical IOLEAgNPs reduced this degeneration impact on renal tissue. Proven that plant-source synthesized IOLEAgNPs play a preventive role as antimalarial agents in female mice infected with P. chabaudi.

Chronic kidney disease amplifies severe kidney injury and mortality in a mouse model of skin arsenical exposure.

In previously published work, we elucidated the role of cutaneous arsenical exposure in promoting acute kidney injury (AKI) in adult healthy mice. Here, we determine whether pre-existing chronic kidney disease (CKD) increases the severity of AKI. Following exposure to aristolochic acid (AA) (a nephrotoxic phytochemical in humans), mice manifested classical markers of CKD, including robust interstitial fibrosis and loss in kidney function. Skin challenge with phenylarsine oxide (PAO), a surrogate for warfare arsenicals, led to significantly worse kidney injury, as evidenced by tubulointerstitial fibrosis, glomerulosclerosis, a persistent loss of estimated glomerular filtration rate and mortality in AA-induced CKD mice compared to mice without CKD. These PAO-challenged CKD mice exhibited enhanced production of serum/urine NGAL, and a significant rise in serum creatinine along with histological markers of kidney injury, including brush border loss, tubular atrophy, cast formation, glomerular injury, and interstitial inflammatory cell infiltration. Serum cytokines IL-4, IL-6, IFN-γ, IL-12p70, TNF-α, and IL-18 significantly elevated in CKD mice following PAO exposure when compared to animals exposed to PAO alone. Furthermore, we found increased TUNEL-positive tubular cells in the kidneys of CKD mice following PAO exposure, suggesting enhanced PAO-mediated cell death in CKD mice. Mechanistically, we determined that DNA damage-regulated p53 signaling was a major mediator of cellular responses to PAO in CKD mice. In summary, our data demonstrate that CKD significantly increased severity of AKI following exposure to arsenicals and suggest that human populations with preexisting CKD could be highly susceptible to arsenical-mediated kidney injury and associated morbidity and mortality.

B-311 Relation of Free Immunoglobulin Ligh Chain Concentration to Overflow Proteinuria

Abstract Background Free immunoglobulin light chains are small proteins that undergo substantial glomerular filtration. When high serum concentrations of free light chains occur in multiple myeloma, the high filtered load of light chains exceeds the uptake capacity of proximal tubules, and overflow proteinuria ensues. Massive excretion of light chains can lead to cast formation and renal injury. The present study sought to determine the relation of serum light chain concentration to overflow proteinuria. Methods Results for patients with plasma cell disorders were reviewed as approved by an institutional review board. A Binding Site Optilite analyzer measured serum free light chain concentrations. Urine and serum protein electrophoresis were performed on Helena agarose gels. A total of 170 paired serum and 24-hour urine specimens were evaluated for 36 patients with increased kappa light chains and 26 patients with increased lambda light chains. Results Overflow proteinuria with either immunoglobulin light chain presented with light chain as the major urinary protein and limited increases of urinary albumin. Light chain excretion exceeded albumin excretion when light chain excretion surpassed 100 mg/d. Similar results were obtained for cases with increased kappa and lambda free light chains. There was a general relation of increased serum kappa and lambda light chains and urinary excretion of the corresponding light chain. Limited urinary excretion of light chains (<120 mg/d) was seen when the serum light chain concentration was < 250 mg/L, representing an approximate threshold for substantial overflow proteinuria. Overflow proteinuria exceeding 2,000 g/d was seen only when serum free light chain concentrations exceeded 800 mg/L. However, a few patients with high serum light chain values (>1,000/L) had low urinary light chain excretion that was discordant from the relation of serum light chain concentration to light chain excretion. Serum light chain values >4,000 mg/L (N = 10) were all associated with overflow proteinuria of > 1,500 mg/d and, in 7 cases, >10,000 mg/d. In a few cases, there was evidence that serum light chain assays overestimated light chain concentrations. In one case, the serum free light chain value was twice the total protein and about 12-fold higher than the serum M-spike, suggestive of substantial overestimation. Conclusions Defining the relation between serum free light chain concentrations and the magnitude of overflow proteinuria helps identify patients at low and high risk of massive overflow proteinuria that can cause renal injury. Limited overflow proteinuria (<120 mg/d) occurred when serum light chain concentration was < 250 mg/L, and substantial overflow proteinuria occurred when serum light chains exceeded 4,000 mg/L Serum free light chain concentrations above 250 mg/L were incompletely predictive of urinary free light chain excretion; a few discordant cases with high measured serum light chain concentrations (>1,000 mg/L) and low excretion of light chains were observed. Further investigation is indicated for cases with possible overestimation of free light chains or discordance between serum light chain values and urinary light chain excretion. Unexpected results in some cases could relate to polymerization of free light chains as previously reported.

Intertwined Critical Realms: Caste, Babas, Deras, and Social Capital Formation in Punjab (India)

Deras are generally perceived as an alternative socio-religious space frequented mostly by lower castes and economically weaker sections of society. They promise to make a significant difference to the lives of such vulnerable sections of society by lending them much needed spiritual, moral, and social support. Within the sprawling premises of Deras, downtrodden find a welcoming ‘counter-public’ enriched with social capital, which offers them an egalitarian domain free from the afflictions of caste discriminations, social exclusion, and subtle indignities often faced by them within the mainstream religious spheres. The growth of Deras thus may be seen as an index of subaltern socio-cultural and syncretic religious realms generating a rich haul of social capital.

High buttocks supine position to reduce small bowel exposure in gynecological radiotherapy

PurposeTo minimize radiation exposure to the small bowel (SB) in patients undergoing treatment for gynecological tumors by adopting a comfortable positioning method.Methods and patientsAll 76 women undergoing Intensity-Modulated Radiation Therapy (IMRT) were included in this study. Patients were immobilized in a supine position using a vacuum bag and thermoplastic cast formation. In the trial group (n = 36), patients raised their buttocks and a solid foam pad was placed under the sacral tail before immobilization. The control group (n = 40) received treatment in the standard supine position. The SB was delineated from the pubic symphysis to the total iliac bifurcation in computed tomography (CT) scans.ResultIn the trial group, a significant reduction in SB volume within the pelvic cavity was observed (mean 399.17 ± 158.7 cc) compared to the control group (mean 547.48 ± 166.9 cc), with a p-value less than 0.001. The trial group showed a statistically significant reduction in the absolute volume of irradiated SB at each dose, ranging from the low dose (10 Gy) to the high dose (45 Gy). In the control group, a negative correlation was found between SB and bladder volumes (R = -0.411, P = 0.008), whereas in the trial group, this correlation was weaker (R = -0.286, P = 0.091), with no significant relationship observed between bladder volume and SB.ConclusionThe high buttocks supine position effectively reduces SB radiation exposure without the need for bladder distension. This positioning method holds promise for reducing SB irradiation in various pelvic tumors.

Caste, gender, race: Signposts of a feminist anti-caste approach

This commentary responds to the essay by Suraj Yengde titled ‘Race and Caste in the Making of US Sociology’, picks up a few threads in Yengde’s argument and attempts to unravel them in the interests of deepening this conversation on an issue that has returned to the foreground of global sociology and anthropology. Given the thin and tenuous disciplinary separations between sociology and social anthropology in India, especially evident in studies on caste, this commentary straddles these two disciplines in the Indian context and points to some interesting disciplinary intersections in the American context. Specifically, Yengde’s discussion of questions of caste, race and class is extended to look at Indian and diasporic contexts to speak to the specific intersections of caste, race, gender, class, region and temporality in contexts of caste formation drawing on the work of Joan Mencher and Gail Omvedt, among others.

Abstract MP31: The effect of dual SGLT1/2 inhibition on the progression of salt-sensitive hypertension

The dual inhibition of sodium-glucose co-transporter 1 and 2 (SGLT1/SGLT2) presents a novel therapeutic approach to cardiovascular diseases. The FDA recently approved the dual SGLT1/2 inhibitor sotagliflozin (Sota) for treating heart failure regardless of ejection fraction. However, our understanding of the effects and mechanisms of SGLT2 and dual SGLT1/2 inhibitors in salt-sensitive hypertension (SS HTN) remains limited. Thus, additional studies are needed to reveal the role and mechanism(s) of SGLTi in SS hypertension. In our previous studies, we demonstrated the beneficial effect of SGLT2i dapagliflozin (Dapa) on SS HTN in male and female Dahl SS rats on blood pressure (MAP after 3 weeks on high salt diet were: Dapa vs. vehicle: 136 ± 3 vs. 156 ± 6 mmHg in males and 140 ± 5 vs. 160±9 mmHg in females). This study aims to define the effects and potential mechanisms of dual SGLT1/2 inhibition in managing SS HTN. Dual SGLT1/2 inhibition with Sota (30 mg/kg/day) prevented the development of SS HTN in Dahl SS in both sexes without changes in heart rate. By the 21 st day of the high-salt challenge, MAP was lower more than 30 mmHg in treated groups (Sota vs. vehicle: male rats 126 ± 2 vs 157 ± 5 mmHg (N=7, p=0.0002); female rats 126 ± 3 vs 167 ± 10 mmHg (N=6, p=0.0095). Under Sota treatment, rats had significantly increased diuresis (Sota vs. vehicle: males 69 ± 3 vs 35 ± 2 ml and females 48 ± 5 vs 31 ± 2 ml on day 21), glucose and sodium excretion. In both sexes, Sota treatment resulted in a lower heart-to-body weight ratio, and kidney weight was not changed. Also, Sota attenuated kidney fibrosis and protein cast formation (Sota vs. vehicle: cortex fibrosis in males 2.3 ± 0.4 vs 4.6 ± 0.5 % and females 2.0 ± 0.2 vs 4.0 ± 0.7 %, outer medullary protein casts in males 2.5 ± 0.2 vs 16.0 ± 2.6 % and 1.9 ± 0.3 vs 7.5 ± 0.9 % in females) without changes in albuminuria in both sexes. However, no changes in glomerular filtration rate or creatine clearance were detected. Based on our data, it can be inferred that dual SGLT1/2 inhibition prevents the development of SS HTN and kidney damage. Potential mechanisms underlying those beneficial effects of SGLT1/2 inhibition will be further explored.

Nandrolone decanoate induced kidney injury through miRNA-146a targeting IRAK1 and TRAF6 via activation of the NF-κB pathway: The effect of moderate exercise

Anabolic-androgenic steroids (AAS) abuse is linked to some abnormalities in several tissues including the kidney. However, the precise molecular mediators involved in AAS-induced kidney disorder remain elusive. The main objective of the present study was to investigate the effect of Nandrolone decanoate on kidney injury alone or in combination with moderate exercise and its related mechanisms. Thirty-two male Wistar rats were subdivided randomly into four groups. control (Con), Nandrolone (10 mg/kg)(N), Exercise (Exe), Nandrolone + Exercise (N+Exe). ResultsAfter 6 weeks, nandrolone treatment led to a significant increase in functional parameters such as serum cystatin c, urea, creatinine, albuminuria and Albumin/ creatinine ratio indicating kidney dysfunction. Moreover, nandrolone treatment increased vacuolization, focal inflammation, hemorragia, cast formation fibrosis in the renal tissue of rats. miRNA-146a increased in kidney tissue after nandrolone exposure by using RT-PCR which may be considered idealtheranomiRNAcandidates for diagnosis and treatment.Western blotting indicated that IRAK1, TRAF6, TNF-α, NF-κB, iNOS and TGF-β protein expressions were considerably elevated in the kidneys of nandrolone treated rats. Moderate exercise could alleviate the renal dysfunction, histological abnormalities and aforementioned proteins. Our findings suggested that nandrolone consumption can cause damage to kidney tissue probably through miRNA-146a targeting IRAK1 and TRAF6 via activation of the NF-κB and TGF-β pathway. These results provide future lines of research in the identification of theranoMiRNAs related to nandrolone treatment, which can be ameliorated by moderate exercise.

A translational model of chronic diabetic nephropathy in the Nile grass rat.

Diabetic nephropathy (DN) is a major healthcare challenge for individuals with diabetes and associated with increased cardiovascular morbidity and mortality. The existing rodent models do not fully represent the complex course of the human disease. Hence, developing a translational model of diabetes that reproduces both the early and the advanced characteristics of DN and faithfully recapitulates the overall human pathology is an unmet need. Here, we introduce the Nile grass rat (NGR) as a novel model of DN and characterize key pathologies underlying DN. NGRs spontaneously developed insulin resistance, reactive hyperinsulinemia, and hyperglycemia. Diabetic NGRs evolved DN and the key histopathological aspects of the human advanced DN, including glomerular hypertrophy, infiltration of mononuclear cells, tubular dilatation, and atrophy. Enlargement of the glomerular tufts and the Bowman's capsule areas accompanied the expansion of the Bowman's space. Glomerular sclerosis, renal arteriolar hyalinosis, Kimmelsteil-Wilson nodular lesions, and protein cast formations in the kidneys of diabetic NGR occurred with DN. Diabetic kidneys displayed interstitial and glomerular fibrosis, key characteristics of late human pathology as well as thickening of the glomerular basement membrane and podocyte effacement. Signs of injury included glomerular lipid accumulation, significantly more apoptotic cells, and expression of KIM-1. Diabetic NGRs became hypertensive, a known risk factor for kidney dysfunction, and showed decreased glomerular filtration rate. Diabetic NGRs recapitulate the breadth of human DN pathology and reproduce the consequences of chronic kidney disease, including injury and loss of function of the kidney. Hence, NGR represents a robust model for studying DN-related complications and provides a new foundation for more detailed mechanistic studies of the genesis of nephropathy, and the development of new therapeutic approaches.

Effectiveness of setarud (IMOD™) in attenuating gentamicin-induced nephrotoxicity in male rats

BackgroundGentamicin (GEN) can have serious adverse effects including nephrotoxicity. Setarud (IMOD™) is a new herbal drug with beneficial immune effects, obtained by mixing Tanacetum vulgare (tansy), Rosa canina and Urtica dioica (nettle) extracts as well as selenium, flavonoids and carotenes. This novel study aims to evaluate the effectiveness of Setarud (IMOD™) in attenuating GEN-induced nephrotoxicity in male rats. Twenty-eight adult male Sprague Dawley rats (weighing 180–200 g) were randomly divided into four groups (7 rats in each group): Control, IMOD treated (20 mg/kg body weight), GEN treated (100 mg/kg body weight), and GEN + IMOD co-treated. Injections were done intraperitoneally for 12 days. Serum urea, creatinine (Cr), Cr clearance, malondialdehyde (MDA), reduced glutathione (GSH) level, and activities of antioxidant enzymes Peroxidase (POD), Catalase (CAT), and Glutathione peroxidase (GPx) were measured by the colorimetric method. Volume density of proximal convoluted tubule (PCT), tubular necrosis, tubular cast formation, and leukocytic infiltration were evaluated histopathologically.ResultsIn the GEN group, there were significantly higher serum urea, Cr, and MDA levels with lower Cr clearance, GSH levels, POD, GPx and CAT activities, and PCT volume density with presence of tubular necrosis compared to the control and IMOD groups (P < 0.05). Treatment with IMOD significantly reduced the levels of urea, Cr and MDA, and increased Cr clearance and the activities of POD and CAT enzymes (P < 0.05). No significant differences in the activity of GSH and GPx were reported in the GEN + IMOD co-treated group compared to the GEN group. Moreover, IMOD significantly ameliorated PCT volume density and renal lesions caused by GEN.ConclusionIMOD (20 mg/kg body weight) can attenuate GEN-induced nephrotoxicity in rats by inhibition of oxidative stress or increasing the normal activity of antioxidant enzymes. Further studies are recommended on the effects of different doses of IMOD.

The Effect of L-Carnitine on Critical Illnesses Such as Traumatic Brain Injury (TBI), Acute Kidney Injury (AKI), and Hyperammonemia (HA).

L-carnitine (LC) through diet is highly beneficial for critical patients. Studies have found that acetyl-L-carnitine (ALC) can reduce cerebral edema and neurological complications in TBI patients. It significantly improves their neurobehavioral and neurocognitive functions. ALC has also been shown to have a neuroprotective effect in cases of global and focal cerebral ischemia. Moreover, it is an effective agent in reducing nephrotoxicity by suppressing downstream mitochondrial fragmentation. LC can reduce the severity of renal ischemia-reperfusion injury, renal cast formation, tubular necrosis, iron accumulation in the tubular epithelium, CK activity, urea levels, Cr levels, and MDA levels and restore the function of enzymes such as SOD, catalase, and GPx. LC can also be administered to patients with hyperammonemia (HA), as it can suppress ammonia levels. It is important to note, however, that LC levels are dysregulated in various conditions such as aging, cirrhosis, cardiomyopathy, malnutrition, sepsis, endocrine disorders, diabetes, trauma, starvation, obesity, and medication interactions. There is limited research on the effects of LC supplementation in critical illnesses such as TBI, AKI, and HA. This scarcity of studies highlights the need for further research in this area.

Unusual Case of Vaginal Bleeding in A Teenager Caused by Endometrial Cast: Case Report and Literature Review

Introduction Endometrial cast, a rare occurrence in gynaecology, is the expulsion of the near entirety of the endometrial lining of the uterine cavity, often maintaining the shape of the uterus. Also known as membranous dysmenorrhoea and largely associated with use of a progesterone-containing contraceptive; some cases following oral contraceptive pills (OCP) use in adolescence for the management of heavy menstrual bleeding (HMB), have been reported. Case Report A 16-year-old nulliparous girl presented with a sudden passage of tissue per vagina (PV) following a short duration of PV bleeding and short-lasting crampy abdominal pain, after a 3-month regular use of Rigevidon® (a combined oral contraceptive pill (OCP) containing ethinylestradiol and levonorgestrel): a contraceptive choice. Noted was a previously normal menstrual cycle following menarche at age 12 with an unremarkable past medical history, a negative urine pregnancy test and an empty uterus on ultrasound scan. Histological examination of the 14cm-long flat fleshy mass with an intrauterine outline confirmed an endometrial or decidual cast. Discussion Cast formation, with different underlying mechanisms – inadequate estrogen opposition effect on endometrium from dysfunctional oestrogen-progesterone imbalance +/- dysfunctional progesterone-mediated cellular Tissue inhibitors to- and matrix metallopeptidases (TIMP/MMP) – has been associated with HMB, ectopic gestations, miscarriages and secondary postpartum haemorrhage. Our case had no preceding significant risk factors and inadequate sonographic-evidence- a common occurrence in literature. This led to diagnostic and management challenges, increasing anxiety and treatment morbidity. Management in young women should be expectant +/- hormonal treatment. Reassurance with individualised progestogens type and dose will aid contraceptive-compliance. Conclusion While endometrial/decidual cast is not associated with a deleterious health effect, it can be distressing to patients and a diagnostic challenge to clinicians, unfamiliar with it. More research into underpinning pathways and disease associations is needed.

Effect of verbascoside against acute kidney injury induced by rhabdomyolysis in rats.

Rhabdomyolysis is a pathological condition caused by muscle tissue degradation. In this condition, intracellular contents enter the bloodstream, and acute kidney injury (AKI) develops. Verbascoside (VB) is one of the most common phenylethanoid glycosides and has antioxidant and anti-inflammatory effects. This study investigated the effects of VB on AKI induced by rhabdomyolysis in rats. Male Wistar rats were divided into six groups (n = 6): (1) control group (normal saline), (2) 50% glycerol (10 ml/kg, IM, single injection, only on the first day), (3)-(5) 50% glycerol (same as group 2) + VB (30, 60, and 100 mg/kg, IP, 4 days), and (6) VB (100 mg/kg). Serum and kidney tissue samples were collected on day 5. Subsequently, serum creatinine (Cr), blood urea nitrogen (BUN), renal glutathione (GSH), malondialdehyde (MDA), lipocalin associated with neutrophil gelatinase (NGAL), tumor necrosis factor-alpha (TNF-α), and pathological changes were investigated. The injection of glycerol elevated levels of kidney damage markers, including Cr and BUN in serum, MDA, TNF-α, and NGAL, along with a reduction in GSH levels in the kidney tissue. The administration of VB (100 mg/kg) significantly lowered the levels of these markers, indicating the therapeutic effect of VB against AKI caused by rhabdomyolysis. Histopathological examinations revealed enhanced myoglobin cast formation and tubular necrosis in the glycerol group, which was reduced in rats that received VB, although this reduction did not reach statistical significance. VB can reduce rhabdomyolysis-induced AKI through its anti-inflammatory and antioxidant effects and decrease kidney damage severity.

Megalin-related mechanism of hemolysis-induced acute kidney injury and the therapeutic strategy.

Hemolysis-induced acute kidney injury (AKI) is attributed to heme-mediated proximal tubule epithelial cell (PTEC) injury and tubular cast formation due to intratubular protein condensation. Megalin is a multiligand endocytic receptor for proteins, peptides, and drugs in PTECs and mediates the uptake of free hemoglobin and the heme-scavenging protein α1-microglobulin. However, understanding of how megalin is involved in the development of hemolysis-induced AKI remains elusive. Here, we investigated the megalin-related pathogenesis of hemolysis-induced AKI and a therapeutic strategy using cilastatin, a megalin blocker. A phenylhydrazine-induced hemolysis model developed in kidney-specific mosaic megalin knockout (MegKO) mice confirmed megalin-dependent PTEC injury revealed by the co-expression of kidney injury molecule-1 (KIM-1). In the hemolysis model in kidney-specific conditional MegKO mice, the uptake of hemoglobin and α1-microglobulin as well as KIM-1 expression in PTECs was suppressed, but tubular cast formation was augmented, likely due to the nonselective inhibition of protein reabsorption in PTECs. Quartz crystal microbalance analysis revealed that cilastatin suppressed the binding of megalin with hemoglobin and α1-microglobulin. Cilastatin also inhibited the specific uptake of fluorescent hemoglobin by megalin-expressing rat yolk sac tumor-derived L2 cells. In a mouse model of hemolysis-induced AKI, repeated cilastatin administration suppressed PTEC injury by inhibiting the uptake of hemoglobin and α1-microglobulin and also prevented cast formation. Hemopexin, another heme-scavenging protein, was also found to be a novel ligand of megalin, and its binding to megalin and uptake by PTECs in the hemolysis model were suppressed by cilastatin. Mass spectrometry-based semiquantitative analysis of urinary proteins in cilastatin-treated C57BL/6J mice indicated that cilastatin suppressed the reabsorption of a limited number of megalin ligands in PTECs, including α1-microglobulin and hemopexin. Collectively, cilastatin-mediated selective megalin blockade is an effective therapeutic strategy to prevent both heme-mediated PTEC injury and cast formation in hemolysis-induced AKI. © 2024 The Pathological Society of Great Britain and Ireland.

A gradient model of renal ischemia reperfusion injury to investigate renal interstitial fibrosis.

Background: The progression from acute kidney injury to chronic kidney disease poses a significant health challenge. Nonetheless, a constraint in existing animal models of renal ischemia/reperfusion (I/R) injury is the necessity for a severe injury, almost reaching a life-threatening level, to trigger the subsequent onset of renal fibrosis. Hence, we explored an adapted gradient approach to induce I/R injury, aiming to promote the progression of renal fibrosis while preserving the overall normal functioning of the kidney. Methods: In each group, 6-8 male C57BL/6 mice were used for model construction, with all undergoing sodium pentobarbital anesthesia and left kidney removal. Subsequently, a silk thread was passed beneath the lower renal branch, elevating the right kidney under a 20-g weight's tension via a pulley system for durations of 30, 40, or 60min. Afterwards, we lowered the kidney, sutured the wound, and administered intraperitoneal saline. Mice in different groups were euthanized following reperfusion for 1, 3, 7, or 28days. Results: We observed a complete cessation of blood flow in the lower pole, while an incomplete cessation in the upper pole in the elevated kidney. Significant renal impairment was evident on day 1 with a 60min ischemic period (187.0 ± 65.3 vs 17.9 ± 4.8μmol/L serum creatinine in normal; p < .001), but not with 30 or 40min. On day 1, tubular necrosis and hyaline cast formation was evident in both lower and upper poles. On day 3, renal function returned to normal and remained normal through day 28. Histologic damage resolved in the upper pole over days 3 to 7, resulting in normal histology on day 28. By contrast, there was sustained tubular damage tubular in the lower pole on days 3 and 7, which failed to resolve and led to significant renal fibrosis by day 28. Conclusion: We created a model demonstrating clinically "silent" renal fibrosis.

Dynamic Evolution of Repetitive Elements and Chromatin States in Apis mellifera Subspecies.

In this study, we elucidate the contribution of repetitive DNA sequences to the establishment of social structures in honeybees (Apis mellifera). Despite recent advancements in understanding the molecular mechanisms underlying the formation of honeybee castes, primarily associated with Notch signaling, the comprehensive identification of specific genomic cis-regulatory sequences remains elusive. Our objective is to characterize the repetitive landscape within the genomes of two honeybee subspecies, namely A. m. mellifera and A. m. ligustica. An observed recent burst of repeats in A. m. mellifera highlights a notable distinction between the two subspecies. After that, we transitioned to identifying differentially expressed DNA elements that may function as cis-regulatory elements. Nevertheless, the expression of these sequences showed minimal disparity in the transcriptome during caste differentiation, a pivotal process in honeybee eusocial organization. Despite this, chromatin segmentation, facilitated by ATAC-seq, ChIP-seq, and RNA-seq data, revealed a distinct chromatin state associated with repeats. Lastly, an analysis of sequence divergence among elements indicates successive changes in repeat states, correlating with their respective time of origin. Collectively, these findings propose a potential role of repeats in acquiring novel regulatory functions.

Kidney Injury by Unilateral Ureteral Obstruction in Mice Lacks Sex Differences

Introduction: Renal fibrosis is a critical event in the development and progression of chronic kidney disease (CKD), and it is considered the final common pathway for all types of CKD. The prevalence of CKD is higher in females; however, males have a greater prevalence of end-stage renal disease. In addition, low birth weight and low nephron number are associated with increased risk for CKD. This study examined the development and severity of unilateral ureter obstruction (UUO)-induced renal fibrosis in male and female wild-type (ROP +/+) and mutant (ROP Os/+) mice, a mouse model of low nephron number. Methods: Male and female ROP +/+ and ROP Os/+ mice were subjected to UUO, and kidney tissue was collected at the end of the 10-day experimental period. Kidney histological analysis and mRNA expression determined renal fibrosis, tubular injury, collagen deposition, extracellular matrix proteins, and immune cell infiltration. Results: Male and female UUO mice demonstrated marked renal injury, kidney fibrosis, and renal extracellular matrix production. Renal fibrosis and α-smooth muscle actin were increased to a similar degree in ROP +/+ and ROP Os/+ mice with UUO of either sex. There were also no sex differences in renal tubular cast formation or renal infiltration of macrophage in ROP +/+ and ROP Os/+ UUO mice. Interestingly, renal fibrosis and α-smooth muscle actin were 1.5–3-fold greater in UUO-ROP +/+ compared to UUO-ROP Os/+ mice. Renal inflammation phenotypes following UUO were also 30–45% greater in ROP +/+ compared to ROP Os/+ mice. Likewise, expression of extracellular matrix and renal fibrotic genes was greater in UUO-ROP +/+ mice compared to UUO-ROP Os/+ mice. In contrast to these findings, ROP Os/+ mice with UUO demonstrated glomerular hypertrophy with 50% greater glomerular tuft area compared to ROP +/+ with UUO. Glomerular hypertrophy was not sex-dependent in any of the genotypes of ROP mice. These findings provide evidence that low nephron number contributes to UUO-induced glomerular hypertrophy in ROP Os/+ mice but does not enhance renal fibrosis, inflammation, and renal tubular injury. Conclusion: Taken together, we demonstrate that low nephron number contributes to enhanced glomerular hypertrophy but not kidney fibrosis and tubular injury. We also demonstrate that none of the changes caused by UUO was affected by sex in any of the ROP mice genotypes.

СТРАТЕГИЯ ПРОТИВОДЕЙСТВИЯ ПЕНИТЕНЦИАРНОЙ СУБКУЛЬТУРЕ С ПОЗИЦИИ СИСТЕМНОГО АНАЛИЗА

The article analyzes the prison subculture from the standpoint of systems theory. It is noted that the existence of informal strata of convicts and stable prison caste formation can be justified by the laws of synergetics, a science that explains the behavior of dissipative structures. It is shown that the main characteristics of a self-organizing system are characteristic of a prison society structured according to the stratification type. From the point of view of systems theory, possible models of countering the expansion of the prison subculture are considered: 1) destruction of the system; 2) the introduction of innovative elements with the formation of new laws of interaction of individual elements of the system; 3) depriving the self-organizing system of the ability to self-replication. The most acceptable choice in the existing conditions is the last option. The conclusion is made about the prospects of the current penitentiary policy of our state.

Investigation the effects of 2-aminoethoxydiphenyl borate (2-APB) on aminoglycoside nephrotoxicity

ABSTRACT Investigation the protective effect of transient receptor potential channel modulator 2-Aminoethoxydiphenyl Borate (2-APB) on aminoglycoside nephrotoxicity caused by reactive oxygen species, calcium-induced apoptosis and inflammation was aimed. Forty Wistar rats were divided (n=8) as follows: Control group; DMSO group; 2-APB group; Gentamicin group (injected 100 mg/kg gentamicin intramuscularly for 10 days); Gentamicin+ 2-APB group (injected 2 mg/kg 2-APB intraperitoneally, then after 30 minutes 100 mg/kg gentamicin was injected intramuscularly for 10 days). Blood samples were collected for biochemical analyses, kidney tissue samples were collected for light, electron microscopic and immunohistochemical investigations. In gentamicin group glomerular degeneration, tubular dilatation, vacuolization, desquamation of tubular cells and hyaline cast formation in luminal space and leukocyte infiltration were seen. Disorganization of microvilli of tubular cells, apical cytoplasmic blebbing, lipid accumulation, myelin figure like structure formation, increased lysosomes, mitochondrial swelling and disorganization of cristae structures, apoptotic changes and widening of intercellular space were found. TNF-α, IL-6 and caspase 3 expressions were increased. BUN and creatinine concentrations were increased. Increase in MDA levels and decrease in SOD activities were determined. Even though degeneration still continues in gentamicin+2-APB treatment group, severity and the area it occupied were decreased and the glomerular and tubule structures were generally preserved. TNF-α, IL-6, caspase 3 immunoreactivities and BUN, creatinine, MDA concentrations were reduced and SOD activities were increased markedly compared to gentamicin group. In conclusion, it has been considered that 2-APB can prevent gentamicin mediated nephrotoxicity with its anti-oxidant, anti-apoptotic and anti-inflammatory effects.

Urinary liver-type fatty acid binding protein is a biomarker reflecting renal damage and the ameliorative effect of drugs at an early stage of histone-induced acute kidney injury.

Circulated histones play a crucial role in the pathogenesis of infectious diseases and severe trauma, and it is one of the potential molecular targets for therapeutics. Recently, we reported that histone is one of the causative agents for urinary L-FABP increase. However, the mechanism is still unclear, especially in severe cases. We further investigated the mechanism of urinary L-FABP increase using a more severe mouse model with histone-induced kidney injury. This study also aims to evaluate the therapeutic responsiveness of urinary L-FABP as a preliminary study. Human L-FABP chromosomal transgenic mice were administrated 30 mg/kg histone from a tail vein with a single dose. We also performed a comparative study in LPS administration model. For the evaluation of the therapeutic responsiveness of urinary L-FABP, we used heparin and rolipram. The histological change with cast formation as a characteristic of the models was observed in proximal tubules. Urinary L-FABP levels were significantly elevated and these levels tended to be higher in those with more cast formation. Heparin and rolipram had the ameliorative effect of the cast formation induced by histone and urinary L-FABP levels significantly decreased. Histone is one of the causative agents for the increase of urinary L-FABP at an early stage of AKI. In addition, it suggested that urinary L-FABP may be useful as a subclinical AKI marker reflecting kidney damage induced by histone. Furthermore, urinary L-FABP reflected the degree of the damage after the administration of therapeutic agents such as heparin and PDE4 inhibitor.