Clinical and ultrasound characteristics of deep endometriosis affecting sacral plexus.

OBJECTIVE: To describe the sonomorphological changes and appearance of deep endometriosis (DE) affecting the nervous tissue of the sacral plexus (SP). METHODS: This was a retrospective study of symptomatic patients who underwent radical resection of histologically confirmed DE affecting the SP and who had undergone preoperative transvaginal sonography (TVS) between 2019 and 2023. Lesions were described based on the terms and definitions of the International Deep Endometriosis Analysis (IDEA), International Ovarian Tumor Analysis (IOTA) and Morphological Uterus Sonographic Assessment (MUSA) groups. A diagnosis of DE affecting the SP on TVS was made when the sonographic criteria of DE were visualized in conjunction with fibers of the SP and the presence of related symptoms corresponding to sacral radiculopathy. Clinical symptoms, ultrasound features and histological confirmation were analyzed for each patient included. RESULTS: Twenty-seven patients with DE infiltrating the SP were identified in two contributing tertiary referral centers. Median age was 37 (range, 29-45) years and all patients were symptomatic and presented one or more of the following neurological symptoms: dysesthesia in the ipsilateral lower extremity (n = 17); paresthesia in the ipsilateral lower extremity (n = 10); chronic pelvic pain radiating in the ipsilateral lower extremity (n = 9); chronic pain radiating in the pudendal region (n = 8); and motor weakness in the ipsilateral lower extremities (n = 3). All DE lesions affecting the SP were purely solid tumors in the posterior parametrium in direct contact with, or infiltrating, the S1, S2, S3 and/or S4 roots of the SP. The median of the largest diameter recorded for each of the DE nodules was 35 (range, 18-50) mm. Echogenicity was non-uniform in 23 (85%) of the DE nodules, with all but one of these nodules containing hyperechogenic areas. The shape of the lesions was irregular in 24 (89%) cases. Only one lesion exhibited a lobulated form, with all other irregular lesions showing a spiculated appearance. An acoustic shadow was produced in 20 (74%) of the nodules, all of which were internal. On color or power Doppler examination, 21 (78%) of the nodules showed no signal (color score of 1). The remaining six (22%) lesions showed a minimal color content (color score of 2). According to pattern recognition, most DE nodules were purely solid, non-uniform, hypoechogenic nodules containing hyperechogenic areas, with internal shadows and irregular spiculated contours, and were poorly vascularized on color/power Doppler examination. CONCLUSION: The ultrasound finding of a parametrial, unilateral, solid, non-uniform, hypoechogenic nodule with hyperechogenic areas and possible internal shadowing, as well as irregular spiculated contours, demonstrating poor vascularization on Doppler examination in proximity to or involving the structures of the SP, indicates DE affecting the SP. © 2024 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Renin-angiotensin system affects endothelial morphology and permeability of renal afferent arteriole.

The afferent arteriole (AA) is an important regulatory site of renal function and blood pressure. We have demonstrated endothelial fenestration and high permeability in the vicinity of renin granulated epithelioid cells in the juxtaglomerular portion of the afferent arteriole in different mammals. The permeability of fenestrated endothelium of afferent arteriole may be important in connection to various physiologic and pathophysiologic processes. We have assumed that the permeable fenestration may serve as a communication channel between the intravascular circulation and a pathway for renin secretion. Utilising the multiphoton image technique we were able to visualise the endothelial fenestration and renin granules of the in vitro microperfused AA and in vivo AA. We demonstrated that ferritin-positive, i.e., permeable portion of the afferent arteriole, under control conditions is on average 45 microm, which is about one-third to half of the total length of the afferent arteriole. The length of this portion is not constant and can change by physiologic and pharmacologic manipulation of renin formation. The permeability of the afferent arteriole is not changing only parallel with the pharmacologically stimulated renin secretion as already demonstrated in adult rats, but also with the change of renin appearance in afferent arteriole within the very first few days of life after birth. Independently from the age there is a significant correlation between the renin-positive and permeable portion of the AA. Further studies are necessary to clarify the physiological significance of afferent arteriolar permeability and its changes in the postnatal development of the kidney, as well as in correlation with activity of renin- angiotensin system.

Angiotensin II activates plasminogen activator inhibitor-I promoter in renal tubular epithelial cells via the AT1 receptor.

BACKGROUND: Plasminogen activator inhibitor-1 (PAI-1) regulates normal extracellular matrix (ECM) metabolism and it is a key regulator of the fibrotic process. Both angiotensin II (Ang II) and angiotensin IV (Ang IV) have been reported to stimulate PAI-1 expression. It is not known how PAI-1 expression is regulated by the renin-angiotensin system (RAS) in renal tubular cells. METHODS: To dissect signaling mechanisms contributing to the up-regulation of the PAI-1 promoter, porcine proximal tubular cells stably expressing the rabbit AT1 receptor (LLC-PK/AT1) were transiently transfected with a luciferase reporter construct containing the PAI-1 promoter. Promoter activation was assessed by measuring luciferase activity from cell lysates. RESULTS: Ang II dose-dependently stimulated the transcriptional activity of the PAI-1 promoter in renal proximal tubular cells whereas Ang IV had no consistent effect on the promoter activity. Neither inhibition of the Extracellular Signal Regulated Kinase (ERK) cascade nor inhibition of the c-Jun-N-terminal Kinase (JNK) pathway did reduce the stimulation of the PAI-1 promoter by Ang II. However, genistein, a tyrosine kinase inhibitor blocked the effect of Ang II. CONCLUSION: Ang II but not Ang IV activates the PAI-1 promoter in renal proximal tubular cells and this effect is mediated by tyrosine kinases.

Unraveling the relationship between macula densa cell volume and luminal solute concentration/osmolality.

At the macula densa, flow-dependent changes in luminal composition lead to tubuloglomerular feedback and renin release. Apical entry of sodium chloride in both macula densa and cortical thick ascending limb (cTAL) cells occurs via furosemide-sensitive sodium-chloride-potassium cotransport. In macula densa, apical entry of sodium chloride leads to changes in cell volume, although there are conflicting data regarding the directional change in macula densa cell volume with increases in luminal sodium chloride concentration. To further assess volume changes in macula densa cells, cTAL-glomerular preparations were isolated and perfused from rabbits, and macula densa cells were loaded with fluorescent dyes calcein and 1-(4-trimethylammoniumphenyl)-6-phenyl-1,3,5-hexatriene p-toluenesulfonate. Cell volume was determined with wide-field and multiphoton fluorescence microscopy. Increases in luminal sodium chloride concentration from 0 to 80 mmol/l at constant osmolality led to cell swelling in macula densa and cTAL cells, an effect that was blocked by luminal application of furosemide. However, increases in luminal sodium chloride concentration from 0 to 80 mmol/l with concomitant increases in osmolality caused sustained decreases in macula densa cell volume but transient increases in cTAL cell volume. Increases in luminal osmolality with urea also resulted in macula densa cell shrinkage. These studies suggest that, under physiologically relevant conditions of concurrent increases in luminal sodium chloride concentration and osmolality, there is macula densa cell shrinkage, which may play a role in the macula densa cell signaling process.

Current mechanisms of macula densa cell signalling.

Macula densa cells couple renal haemodynamics, glomerular filtration and renin release with tubular fluid salt and water reabsorption. These cells detect changes in tubular fluid composition through a complex of intracellular signalling events that are mediated by membrane transport pathways. Increases in luminal fluid sodium chloride concentration result in alterations in cell sodium chloride concentration, cytosolic calcium, cell pH, basolateral membrane depolarization and cell volume. Macula densa signalling then involves the production and release of specific paracrine signalling molecules at their basolateral membrane. Upon moderate increases in luminal sodium chloride concentration macula densa cells release increasing amounts of ATP and decreasing amounts of prostaglandin E(2), thereby increasing afferent arteriolar tone and decreasing the release of renin from granular cells. On the other hand, further increases in luminal concentration stimulate the release of nitric oxide, which serve to prevent excessive tubuloglomerular feedback vasoconstriction. Paracrine signalling by the macula densa cells therefore controls juxtaglomerular function, renal vascular resistance and participates in the regulation of renin release.