Connective Tissue Components Research Articles

Phosphate overload via the type III Na-dependent Pi transporter represses aortic wall elastic fiber formation.

Phosphate (Pi) induces differentiation of arterial smooth muscle cells to the osteoblastic phenotype by inducing the type III Na-dependent Pi transporter Pit-1/solute carrier family member 1. This induction can contribute to arterial calcification, but precisely how Pi stress acts on the vascular wall remains unclear. We investigated the role of extracellular Pi in inducing microstructural changes in the arterial wall. Aortae of Pit-1-overexpressing transgenic (TG) rats and their wild-type (WT) littermates were obtained at 8 weeks after birth. The thoracic descending aorta from WT and TG rats was used for the measurement of wall thickness and uniaxial tensile testing. Structural and ultrastructural analyses were performed using light microscopy and transmission electron microscopy. Gene expression of connective tissue components in the aorta was quantified by quantitative real-time polymerase chain reaction. Aortic wall thickness in TG rats was the same as that in WT rats. Uniaxial tensile testing showed that the circumferential breaking stress in TG rats was significantly lower than that in WT rats (p<0.05), although the longitudinal breaking stress, breaking strain, and elastic moduli in both directions in TG rats were unchanged. Transmission electron microscopy analysis of the aorta from TG rats showed damaged formation of elastic fibers in the aortic wall. Fibrillin-1 gene expression levels in the aorta were significantly lower in TG rats than in WT rats (p<0.05). Pi overload acting via the arterial wall Pit-1 transporter weakens circumferential strength by causing elastic fiber malformation, probably via decreased fibrillin-1 expression.

Unveiling putative modulators of mutable collagenous tissue in the brittle star Ophiomastix wendtii: an RNA-Seq analysis

Collagenous connective tissue, found throughout the bodies of metazoans, plays a crucial role in maintaining structural integrity. This versatile tissue has the potential for numerous biomedical applications, including the development of innovative collagen-based biomaterials. Inspiration for such advancements can be drawn from echinoderms, a group of marine invertebrates that includes sea stars, sea cucumbers, brittle stars, sea urchins, and sea lilies. Through their nervous system, these organisms can reversibly control the pliability of their connective tissue components (i.e., tendons and ligaments) that are composed of mutable collagenous tissue (MCT). The variable tensile properties of the MCT allow echinoderms to perform unique functions, including postural maintenance, reduction of muscular energy use, autotomy to avoid predators, and asexual reproduction through fission. The changes in the tensile strength of MCT structures are specifically controlled by specialized neurosecretory cells called juxtaligamental cells. These cells release substances that either soften or stiffen the MCT. So far, only a few of these substances have been purified and characterized, and the genetic underpinning of MCT biology remains unknown. Therefore, we have conducted this research to identify MCT-related genes in echinoderms as a first step towards a better understanding of the MCT molecular control mechanisms. Our ultimate goal is to unlock new biomaterial applications based on this knowledge. In this project, we used RNA-Seq to identify and annotate differentially expressed genes in the MCT structures of the brittle star Ophiomastix wendtii. As a result, we present a list of 16 putative MCT modulator genes, which will be validated and characterized in forthcoming functional analyses.

Inguinal hernia: a view from the 21st century (a review)

The proposed review is a look at the pathogenesis of inguinal hernia from the standpoint of molecular biology, as well as an attempt to understand the problems that are a consequence of explantation: issues of male fertility, chronic inflammation, carcinogenesis. It is proven that the pathogenesis of inguinal hernia is not reduced to a defect of the anterior abdominal wall. Moreover, the formation of this defect is preceded by a complex of modification of connective tissue components, which is based on the separation of the processes of extracellular matrix synthesis and matrix degradation with the predominance of the latter that disrupts the rotation of structures responsible for mechanical strength and elasticity. From this point of view, inguinal hernia is a multifactorial and heterogeneous disease.

The role of collagen in joint disorders: Applications in orthopedics, rheumatology, and sports medicine

Joint diseases are prevalent in orthopedic, rheumatological, and sports medicine fields, significantly impacting patients' quality of life. Collagen, a primary component of connective tissues, has emerged as a therapeutic agent for these conditions. This article explores the applications of collagen in joint diseases, comparing oral and intra-articular administration, evaluating optimal dosages, assessing single versus long-term therapies, discussing side effects, and examining the benefits of hydrolyzed versus non-hydrolyzed collagen. Additionally, explore various sources of collagen and their respective advantages for patient care.

Effect of photobiomodulation with different wavelengths on periodontal repair in non-hyperglycemic and hyperglycemicrats.

Hyperglycemic conditions is associated with more severe periodontitis and poorer outcomes after nonsurgical periodontal treatment (NPT). Then, these patients are candidates for adjunctive therapy associated with NPT. This study evaluates the effect of photobiomodulation (PBMT) at different wavelengths on periodontal repair in non-hyperglycemic/hyperglycemic animals. Sixty-four rats were submitted to induction of periodontitis by ligatures. Hyperglycemia was induced in half of these animals, whereas the other half remained non-hyperglycemic. The animals were subdivided into 4 groups according to the PBMT protocol applied at the time of ligature removal (n = 8): CTR: Without PBMT; IRL: PBMT with infrared laser (808 nm); RL: PBMT with red laser (660 nm); and RL-IRL: PBMT with red (660 nm) and infrared laser (808 nm). After a period of 7 days, the animals were euthanized. The parameters assessed by microtomography were the bone volume relative to total tissue volume (BV/TV%), distance from the cemento-enamel junction to the top of the bone crest (CEJ-CB), trabecular thickness, space between trabeculae, and number of trabeculae. Additionally, the percentage of inflammatory cells, blood vessels, and connective tissue matrix were assessed by histomorphometric analysis. PBMT reduced bone loss and increased trabecular density in hyperglycemic animals (p < .05), with RL being more effective in reducing linear bone loss (CEJ-CB), whereas RL-IRL was more effective in maintaining BV/TV%. PBMT reduced blood vessels and increased the connective tissue component in hyperglycemic animals (p < .05). RL-IRL reduced inflammatory cells regardless of the systemic condition of the animal (p < .05). PBMT (RL, RL-IRL) improves the repair of periodontal tissues in hyperglycemic animals.

Reviewing hereditary connective tissue disorders: Proposals of harmonic medicolegal assessments.

Hereditary connective tissue disorders (HCTDs) are a heterogeneous group of inherited diseases. These disorders show genetic mutations with loss of function of primary components of connective tissue, such as collagen and elastic fibers. There are more than 200 conditions that involve hereditary connective tissue disorders, while the most known are Marfan syndrome, Osteogenesis Imperfecta, and Ehlers-Danlos syndromes. These disorders need continuous updates, multidisciplinary skills, and specific methodologic evaluations sharing many medicolegal issues. Marfan syndrome and Ehlers-Danlos syndromes show a high risk of early sudden death. As a consequence of this, postmortem genetic testing can identify novel genotype-phenotype correlations which help the clinicians to assess personalized cardiovascular screening programs among the ill subjects. Genetic testing is also essential to identify children suffering from Osteogenesis Imperfecta, especially when a physical abuse is clinically suspected. However, this is a well-known clinical problem even though there are still challenges to interpret genetic data and variants of unknown significance due to the current extensive use of new genetic/genomic techniques. Additionally, the more significant applications and complexities of genomic testing raise novel responsibilities on the clinicians, geneticists, and forensic practitioners as well, increasing potential liability and medical malpractice claims. This systematic review provides a detailed overview on how multidisciplinary skills belonging to clinicians, medicolegal consultants, radiologists, and geneticists can cooperate to manage HCTDs from autopsy or clinical findings to genetic testing. Thus, technical aspects need to be addressed to the medicolegal community since there is no consensus works or guidelines which specifically discuss these issues.

The expression of intermediate filaments in the abomasum of ruminants: A comparative study.

Intermediate filaments (IFs) are key molecular factors of the cell and have been reported to play an important role in maintaining the structural integrity and functionality of the abomasum. This study was designed to determine the regional distribution, cellular localization and expression of several IFs, including CK8, CK18, CK19, vimentin, desmin, peripherin and nestin, as well as the connective tissue component laminin, in the bovine, ovine and caprine abomasa. Immunohistochemical analyses demonstrated varying levels of expression of CK8, CK18, CK19, vimentin, desmin, nestin, peripherin and laminin in the bovine, ovine and caprine abomasa. CK8 immunoreactions were particularly evident in the luminal and glandular epithelia of the glands found in the abomasal cardia, fundus and pylorus in all three species. In the bovine abomasum, CK18 immunoreactions were stronger in the parietal cells, compared to the chief cells. In the abomasum of all three species, the smooth muscle as well as the smooth muscle cells of the vascular media in the cardiac, fundic and pyloric regions showed strong immunoreactivity. In all three species, the cardiac, fundic and pyloric regions of the abomasum showed strong peripherin and nestin immunoreactions in the luminal and glandular epithelial cells, stromal and smooth muscle cells, nervous plexuses and blood vessels. The expression patterns of IFs and laminin in the ruminant abomasum suggest that these proteins play a structural role in the cytoskeleton and are effective in maintaining abomasal tissue integrity and stability.

Meningothelial hamartoma of scalp mimicking encephalocele in an infant: A case report and review of literature.

An extremely rare benign lesion of the scalp is reported in a 2-month-old infant. The lesion had been present since birth. On examination, a 3 × 4 cm skin-colored soft mass over the occipital midline area was observed. On ultrasound, a diagnosis of occipital encephalocele was suggested. A complete excision of the mass was performed. Histological examination showed a subcutaneous lesion, which showed haphazardly arranged epithelioid cell nests admixed with connective tissue components, adipose tissues, and pseudovascular patterns within the deep dermis. Immunohistochemistry showed positive expression of Epithelial membrane antigen (EMA) and Vimentin. Tumor cells showed negative expression for Glial Fibrillary acidic protein (GFAP), chromogranin, S-100, Smooth muscle actin (SMA), and CD 34. Based on the clinical presentation, histologic features, and results of ancillary studies, a diagnosis of meningothelial hamartoma of the scalp was given. The clinical behavior of this lesion is benign but it often causes diagnostic confusion and may mimic malignant tumors. It is crucial to recognize the main features of this lesion.

Three-year outcomes of a randomized clinical trial of perioperative vaginal estrogen as adjunct to native tissue vaginal apical prolapse repair

As the muscular and connective tissue components of the vagina are estrogen responsive, clinicians may recommend vaginal estrogen to optimize tissues preoperatively and as a possible means to reduce prolapse recurrence, but long-term effects of perioperative intravaginal estrogen on surgical prolapse management are uncertain. This study aimed to compare the efficacy of perioperative vaginal estrogen vs placebo cream in reducing composite surgical treatment failure 36 months after native tissue transvaginal prolapse repair. This was an extended follow-up of a randomized superiority trial conducted at 3 tertiary US sites. Postmenopausal patients with bothersome anterior or apical vaginal prolapse were randomized 1:1 to 1-g conjugated estrogen cream (0.625 mg/g) or placebo, inserted vaginally twice weekly for ≥5 weeks preoperatively and continued twice weekly for 12 months postoperatively. All participants underwent vaginal hysterectomy (if the uterus was present) and standardized uterosacral or sacrospinous ligament suspension at the surgeon's discretion. The primary report's outcome was time to failure by 12 months postoperatively, defined by a composite outcome of objective prolapse of the anterior or posterior walls beyond the hymen or the vaginal apex descending below one-third the total vaginal length, subjective bulge symptoms, and/or retreatment. After 12 months, participants could choose to use-or not use-vaginal estrogen for atrophy symptom bother. The secondary outcomes included Pelvic Organ Prolapse Quantification points, subjective prolapse symptom severity using the Patient Global Impression of Severity and the Patient Global Impression of Improvement, and prolapse-specific subscales of the 20-Item Pelvic Floor Distress Inventory and the Pelvic Floor Impact Questionnaire-Short Form 7. Data were analyzed as intent to treat and "per protocol" (ie, ≥50% of expected cream use per medication diary). Of 206 postmenopausal patients, 199 were randomized, and 186 underwent surgery. Moreover, 164 postmenopausal patients (88.2%) provided 36-month data. The mean age was 65.0 years (standard deviation, 6.7). The characteristics were similar at baseline between the groups. Composite surgical failure rates were not significantly different between the estrogen group and the placebo group through 36 months, with model-estimated failure rates of 32.6% (95% confidence interval, 21.6%-42.0%) and 26.8% (95% confidence interval, 15.8%-36.3%), respectively (adjusted hazard ratio, 1.55; 95% confidence interval, 0.90-2.66; P=.11). The results were similar for the per-protocol analysis. Objective failures were more common than subjective failures, combined objective and subjective failures, or retreatment. Using the Patient Global Impression of Improvement, 75 of 80 estrogen participants (94%) and 72 of 76 placebo participants (95%) providing 36-month data reported that they were much or very much better 36 months after surgery (P>.99). These data included reports from 51 of 55 "surgical failures." Pelvic Organ Prolapse Quantification measurements, Patient Global Impression of Severity scores, and prolapse subscale scores of the 20-Item Pelvic Floor Distress Inventory and Pelvic Floor Impact Questionnaire-Short Form 7 all significantly improved for both the estrogen and placebo groups from baseline to 36 months postoperatively without differences between the groups. Of the 160 participants providing data on vaginal estrogen usage at 36 months postoperatively, 40 of 82 participants (49%) originally assigned to the estrogen group were using prescribed vaginal estrogen, and 47 of 78 participants (60%) assigned to the placebo group were using vaginal estrogen (P=.15). Adjunctive perioperative vaginal estrogen applied ≥5 weeks preoperatively and 12 months postoperatively did not improve surgical success rates 36 months after uterosacral or sacrospinous ligament suspension prolapse repair. Patient perception of improvement remained very high at 36 months.

Effects of 32 d of spaceflight on tendon collagen fibril morphology and nanomechanics

INTRODUCTION: Collagen is an essential component of connective tissue and plays a crucial role in elasticity, stability, and force distribution. While the adaptations of tendon to internal stimuli have been extensively researched, the impact of environmental factors (such as microgravity) on its structure and function at the nanoscopic scale (i.e., fibril level) remains largely unexplored. The purpose of this study was to determine the effects of 32 days (d) aboard the International Space Station (ISS) on murine tendon collagen fibril morphology and nanomechanics (Young’s Modulus, YM). We hypothesized there would be a decrease in fibril size and YM after spaceflight. Methods: Quadriceps tendon samples from female C57BL/6J mice from NASA Rodent Research-1 underwent chemical processing and mechanical isolation. Subsequently, collagen fibrils (n=56) were studied via atomic force microscopy (AFM; JPK NanoWizard 4a) to compare the morphology (diameter, height) and nanomechanics (average YM) between spaceflight (SF) and ground control (GC) specimens. The qp-BioAC-CB1 cantilever (spring constant: 0.3 N/m, tip radius: 10μm) was used under quantitative imaging mode (QI) for all force and morphological measurements. The data from 56 micrographs (SF n=30; GC n=26) was processed via the JPK Data Processing Software (Version 6.4.5.), and finally analyzed with Gwyddion (Version 2.62). A 2-way MANOVA compared all measurements. Results: More ‘small fibrils’ (height &lt;50nm) were identified in the SF vs GC samples. SF fibrils averaged 20.3% smaller (width) compared to GC, but this difference was not significant (p&gt;0.05). Additionally, while there was a trend for a lower YM in the SF samples, YM for SF specimens was not statistically different between groups (GC=3.26±1.94 MPa; SF= 2.76±1.44 MPa) (p&gt;0.05). CONCLUSION: To our knowledge, this is the first investigation to use AFM QI-mode on tendon collagen fibrils after spaceflight. While there were no statistically significant changes in mean fibril size and YM between SF and GC, these results suggest that collagen fibrils may require more time to adapt to changes in their environment, and/or more rapid changes may take place at different levels of the collagen hierarchy. Our data provides valuable insight into mammalian tissue adaptations during spaceflight. Future research should continue these investigations with longer-duration missions to build a time-course of tendon adaptations to microgravity. FUNDING: CSUBIOTECH New Investigator Grant (JRB). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Acquired Perforating Dermatosis: Clinical and Histopathological Analysis of 95 Patients From One Center.

Acquired perforating dermatosis (APD) is a disease group characterized by transepidermal elimination of dermal connective tissue materials such as collagen, elastic fibers, and keratin through the epidermis and observed with pruritic skin lesions. In this study, we aim to clarify the clinical, histopathological, and dermoscopic characteristics of APD, identify the associated systemic disease, and figure out treatment options. This study was designed as a single-center retrospective, observational, cross-sectional study. We evaluated all accessible APD cases between January 2004 and June 2022 in a tertiary care hospital. A total of 95 patients with confirmed APD were included in the study. Sixty percent of the patients were women and 40% were men. The median age at diagnosis was 63.1 years (35-85 years). The most common site of lesions was the lower extremities which were detected in 86.31% of the patients. The concomitant systemic disease was identified in 84.21% of the patients. The most common systemic disease was type 2 diabetes mellitus (65.26%). Antihistamines and topical corticosteroids were the most commonly prescribed treatment agents. Transepidermal elimination of dermal connective tissue components is a feature of APD and the disease usually presents with pruritic papules and nodules with central keratotic crust or plug. The diagnosis of APD requires a clinical examination and histological investigation. APD is usually accompanied by systemic comorbidities. There are several topical and systemic medications available for APD, however, sometimes the therapy might be challenging.

Analysis of early morphological and functional perivulnar changes in the mucosa of the cecum after suturing with different surgical threads

The correct choice of suture material is the key to successful treatment in abdominal surgery, particularly pediatric surgery. Given this, experimental studies on the effect of sutures made with different surgical threads are one of the most urgent surgery needs. The aim - to conduct a comparative analysis of early morphological and functional changes in the perivulnar region of the mucosa of the rabbit cecum after suturing with polyglactin-910 and polycaprolactone modified with L-arginine. Materials and methods. The study was conducted on 25 rabbits aged 8-10 months in compliance with all bioethical standards and recommendations. The control group consisted of 5 animals; the first experimental group, in which synthetic surgical polyfilamentous absorbable suture polyglactin-910 was used to close the wound defect, and the second experimental group, in which monofilamentous absorbable suture polycaprolactone modified with L-arginine was used to close the wound defect, consisted of 10 rabbits each. All stages of surgical access and sampling of intact cecal wall tissues were performed in the control group. The rabbits of the experimental groups underwent colotomy followed by suturing of the large intestine with appropriate suture material. Each experimental group was divided into two subgroups (5 rabbits in each), in which the condition of the perivulvar region was studied on days 3 and 7, respectively. The animals were not euthanised; during the second operation, tissues of the cecum were taken from the sutured area and the formed scar at the appropriate time. Histological, semi-thin serial sections, electron microscopic, morphometric, and statistical methods were used. Discussion. The average thickness of the cecal mucosa after colotomy increased significantly on days 3-7 when using both surgical threads, but when using polycaprolactone modified with L-arginine, the above indicator was 63.06% and 22.46% lower, respectively, due to a decrease in hyperhydration of the connective tissue component of the mucosa, leukocyte infiltration in the perivulnar area and acceleration of reparative processes. Conclusions. Polycaprolactone modified with L-arginine has a positive effect on the course of morphological and functional processes in the perivulnar region of the rabbit cecum's mucosa. In terms of its characteristics, it is not worse than polyglactin-910. No conflict of interests was declared by the authors.

The rs2018736 fibulin-5 polymorphism as a determinant for pelvic organ prolapse: a case–control study

Objective Fibulin-5 is a connective tissue component and may play a role in pelvic organ prolapse (POP) pathogenesis. This study aimed to verify the association of the rs2018736 polymorphism of the fibulin-5 gene with POP in postmenopausal Brazilian women, and to determine the risk factors for POP. Method This observational, cross-sectional, case–control study assessed postmenopausal women with advanced POP (stages III and IV) and control women (stages 0 and I) by examination and peripheral blood sample collection. DNA sequences were analyzed by real-time reverse-transcriptase polymerase chain reaction. A logistic regression model was used with p < 0.05 for significance. Results A total of 565 participants were evaluated (325 POP and 240 control). The homozygous C allele of rs2018736 (CC) was protective against POP (odds ratio [OR] 0.49, 95% confidence interval [CI] 0.26–0.91). Age (OR 1.09, 95% CI 1.05–1.13), number of pregnancies (OR 1.14, 95% CI 1.01–1.28), vaginal delivery (OR 5.32, 95% CI 2.58–11.01), forceps delivery (OR 3.34, 95% CI 1.72–6.47), weight of newborn (OR 1.0007, 95% CI 1.0002–1.0011), family history of POP (OR 2.35, 95% CI 1.24–4.44), hypertension (OR 1.74, 95% CI 1.01–3.00) and diabetes (OR 2.19, 95% CI 1.07–4.48)] were independent predictors for POP; cesarean (OR 0.02, 95% CI 0.005–0.09) was protective. Conclusion The rs2018736-CC genotype of the fibulin-5 gene has a protective role against POP.

Effect of quercetin administration on electron microscopic changes in testicular interstitial endocrinocytes during long-term central blockade of luteinising hormone in rats

Quercetin is a flavonoid with potential health benefits and it may help prevent cardiovascular diseases, reduce the risk of degenerative brain processes and cancer, and has antioxidant properties that neutralise free radicals. Substances in this group also have antioxidant properties, which help the body protect itself from the harmful effects of free radicals by neutralising these unstable molecules. Research indicates that the impact of free radicals on cell structure is associated with the development of chronic diseases such as diabetes, cancer, and cardiovascular pathologies. The aim of the study was to investigate the effect of quercetin administration on electron microscopic changes in the interstitial endocrinocytes of the testes under long-term central blockade of the synthesis of luteinising hormone by tryptorelin. The experiment involved 35 sexually mature male white rats. They were divided into two groups: the control group (I) received saline, while group II received subcutaneous injections of tryptorelin at a dose of 0.3 mg of active ingredient per kg of rat body weight to induce experimental central deprivation of luteinising hormone synthesis and additionally, quercetin was administered three times a day by gastric tube in terms of body weight. The study has demonstrated that the administration of tryptorelin results in structural and functional changes in the connective tissue components of rat testes. Specifically, there are quantitative and qualitative disorders in the population of interstitial endocrine cells, as well as electron microscopic changes at the subcellular level. Various pathological changes and abnormalities in the functional activity of the internal components of the cell were detected on days 270 and 365 of the experiment. The frequency, number, and size of Reinke crystals in relation to the cell volume correlated with changes in cells and increased at later stages of the study. A similar correlation with testosterone levels has not been found in the literature, which leads us to classify Reinke crystals as the result of degenerative processes in the cell. Thus, additional administration of quercetin reduces the adverse effect of tryptorelin and delays the onset of changes in the structure of interstitial endocrinocytes from day 180 to later observation periods.

(197) The Impact of Connective Tissue Disorders on Rates of Penile Fracture and Peyronie’s Disease

Abstract Introduction Ehlers Danlos Syndrome (EDS) and collagen-related hypermobility disorders are well known to cause frequent joint dislocations, easy bruising, and poor wound healing. Marfan syndrome is caused by a mutation in the protein fibrillin, a key component of collagen and elastin connective tissue, whose dysfunction causes the marfanoid phenotype. Currently, little is known regarding the impact of connective tissue disorders on men’s sexual health. As a first step in exploring this association, we investigated two physical phenomena that may be impacted by collagen disorders, penile fractures and Peyronie’s disease. Objective This study aims to investigate rates of penile fracture and Peyronie’s disease in EDS and Marfan syndrome patients. Methods A multi-center, international, electronic health record network (TriNetX) was queried to identify adult male patients with or without EDS between 1993 and 2023 using ICD-10 codes Q79.6, Q79.60, and Q79.62 specific for EDS and EDS related hypermobility syndrome. TriNetX was separately queried for Marfan syndrome using ICD-10 code Q87.4. Incidence and prevalence of penile fractures and Peyronie’s disease were compared between patients with and without the diseases of interest. Penile fractures were identified using ICD-10 codes S39.840, S39.84A, S39.84S, S39.84D. Peyronie’s disease was defined using ICD-10 code N48.6. Odds ratios were generated with 95% confidence intervals. All statistical analyses were conducted within the TriNetX platform. Results Data was queried from 82 healthcare organizations to yield 11,937 EDS patients, and from 101 healthcare organizations to yield 13,705 Marfan syndrome patients. 109 healthcare organizations contributed data to yield a control group of 63,790,628 men. Men with EDS had a 25 times higher rate of penile fractures (0.09%) compared to men without EDS (OR 25; 95% CI [13.8-47.8]). Men with Marfan’s syndrome had a 23 times higher rate of penile fractures (0.08%) compared to men without Marfan’s syndrome (OR 23; 95% CI [12.4-43.1]). Men with Marfan’s syndrome also had a significantly higher incidence of Peyronie’s disease compared to men without Marfan’s syndrome (OR 1.9; 95% CI [1.2-3]). The difference in rates of Peyronie’s disease was not significantly higher for men with EDS (OR 1.4; 95% CI [0.8 – 2.5]). Conclusions Patients with EDS and Marfan syndrome are at an over 20 times higher risk for penile fracture. These increased risks may be due to EDS’s and Marfan syndrome’s effects on collagen and fibrillin/elastic fibers, respectively, which are significant structural components of the corpora cavernosa. Patients with these syndromes should be aware of this increased risk and further research is needed to establish how to council these patients about taking appropriate precautions. Disclosure No.

Assessment of IL-8 Levels in Saliva of Healthy and Chronic Periodontitis Individuals

ABSTRACT Inflammation of the gums and other tissues supporting the teeth, as well as gradual loss of attachment and bone, are the results of chronic periodontitis, an infectious illness. During inflammation, a group of low molecular weight proteins called cytokines facilitate a complex interaction between inflammatory cells (such neutrophils) and other cellular components in connective tissue. The cytokine interleukin-8 (IL-8) is a potent neutrophil chemoattractant. Therefore, it is possible that IL-8 is crucial to the development of periodontitis’s pathology. Objectives: 1) To estimate concentration of IL-8 levels in healthy individuals and chronic periodontitis individuals. 2) To compare IL-8 levels in healthy and chronic periodontitis individuals Materials and Methods: Participants in this research will be recruited from among those who visit the outpatient department (OPD) at the NGH Institute of Dental Sciences and Research Centre, Belagavi, run by the Maratha Mandal. Control Group: Subjects with no clinical attachment loss (CAL) and a probing depth of 3.0 mm are considered to be periodontally healthy. Those in Group 2 (chronic periodontitis) have a chronic form of the disease, as shown by a probing pocket depth (PPD) of less than 5 mm and CAL of less than 2 mm. Unstimulated saliva sample will be collected in a 5 mL wide-mouthed sterile container by spitting method. Samples collected will be centrifuged. The supernatant is collected and stored at –80°C and then assayed for IL-8 concentration by using the standardized IL-8 ELISA kit.

Phenomena of Intussusceptive Angiogenesis and Intussusceptive Lymphangiogenesis in Blood and Lymphatic Vessel Tumors.

Intussusceptive angiogenesis (IA) and intussusceptive lymphangiogenesis (IL) play a key role in the growth and morphogenesis of vessels. However, there are very few studies in this regard in vessel tumors (VTs). Our objective is to assess the presence, characteristics, and possible mechanisms of the formation of intussusceptive structures in a broad spectrum of VTs. For this purpose, examples of benign and malignant blood and lymphatic VTs were studied via conventional procedures, semithin sections, and immunochemistry and immunofluorescence microscopy. The results demonstrated intussusceptive structures (pillars, meshes, and folds) in benign (lobular capillary hemangioma or pyogenic granuloma, intravascular papillary endothelial hyperplasia or Masson tumor, sinusoidal hemangioma, cavernous hemangioma, glomeruloid hemangioma, angiolipoma, and lymphangiomas), low-grade malignancy (retiform hemangioendothelioma and Dabska tumor), and malignant (angiosarcoma and Kaposi sarcoma) VTs. Intussusceptive structures showed an endothelial cover and a core formed of connective tissue components and presented findings suggesting an origin through vessel loops, endothelialized thrombus, interendothelial bridges, and/or splitting and fusion, and conditioned VT morphology. In conclusion, the findings support the participation of IA and IL, in association with sprouting angiogenesis, in VTs, and therefore in their growth and morphogenesis, which is of pathophysiological interest and lays the groundwork for in-depth molecular studies with therapeutic purposes.

BIOCHEMICAL MARKERS OF BLOOD SERUM AND ARTICULAR CARTILAGE IN DIFFERENT FORMS OF IDIOPATHIC COXARTHROSIS PROGRESSION

Deformation due to arthrosis of the hip joint affects 40 % of the total number of patients with osteoarthritis, which is from 7 to 25 % of the adult population. For the activity of the pathological process evaluation we studied biochemical changes in the metabolism of collagen, namely: glycosaminoglycans (GAG), hydroxyproline (HP) fractions, collagenase, hyaluronidase activity, etc. Objective. To determine the biochemical changes in blood serum and articular cartilage depending on the form of progression of idiopathic coxarthrosis. Methods. 23 patients were examined (8 (34.8 %) men, 15 (65.2 %) women, age 45‒75 years and more) with idiopathic arthrosis of the hip joint IV stage (Kellgren–Lawrence). Progression forms of idiopathic coxarthrosis were distinguished: group I — rapid (the period from the initial to the final stage of the disease was 5 years and less), II — moderate (5‒10 years), III — slow (over 10 years). Collagenase activity, HP fractions, total GAG content were determined in patients’ blood serum, and collagen content was determined in the cartilage tissue of the femoral head. Results. Compared with the age reference norm in the blood serum of patients of group I activity collagenase increased to 114 %, in II and III — 122 and 135 %, respectively; the content of the free fraction of GP — up to 111, 169, 128 %, respectively; GAG concentrations — up to 110, 122, and 135 %, respectively; protein-bound HP was reduced to 60% in group II, up to 84 % — in group III. In cartilage tissue, the GAG content decreased in group III to 63 %, II — 55 %, I — 47 %; collagen — 32, 25, 24 % in accordance. Conclusions. The course of idiopathic coxarthrosis is determined by metabolic changes in the components of the organic basis of connective and cartilaginous tissues in blood serum. The most profound changes were found in the synthetic phase of HP metabolism, especially in the group with a rapid course disease. A decrease in the content of organic components of connective tissue (GAG and collagen) was determined

Reasons and Mechanisms of Development of Mastopathy (Review of Literature)

This review article examines the relationship between various etiological factors in the development of mastopathy. Multiple exogenous and endogenous risk factors disrupt the normal ratio of sex hormones, causing hyperestrogenism and hyperproliferation of the epithelium in breast tissue, which leads to the development of mastopathy. In the presence of polymorphism of coding genes (ESR1 and PRG), mastopathy also increases the risk of developing breast cancer. Disturbances in the ESR1 receptor gene (Estrogen Receptor 1) lead to changes in the sensitivity of receptors to hormones and even to its loss. According to the literature, polymorphism in the intronic region of the ESR1 gene is associated with the risk of fibrocystic mastopathy. The presence of polymorphism of the PRG (Progesterone Receptor Genes) gene may cause the occurrence of defective forms of PR (Progesterone Receptor) with disruption of the ligand- and hormone-binding zones, which is confirmed by the effects of progesterone in tissues. Thus, progesterone deficiency makes possible excessive proliferation of not only epithelial cells, but also the connective tissue component of the mammary gland. In this case, the expression of the progesterone receptor gene is regulated by the level of estrogen. The association of various combinations of predisposition genes indicates the presence of a specific combination of genotypes for each clinical and pathogenetic variant. In proliferative forms of mastopathy, foci with an excess content of estrogen receptors in the epithelium and high activity of cell proliferation and apoptosis are formed in the breast tissue; there is an increase in the content of alpha-estrogen receptors, a change in the relative content of alpha- and beta-estrogen receptors, A- and B-progesterone receptors; the sensitivity of the epithelium to estradiol increases; a complex of cyclin-dependent kinases, alpha-transforming and epidermal growth factors is activated; the proliferative activity of the epithelium increases; apoptosis processes are disrupted; vascularization of the parenchyma increases. All these pathological mechanisms that increase the risk of breast cancer have not yet been sufficiently studied both at the experimental and clinical level. In the treatment of mastopathy, diet therapy, psychological correction, hormonal drugs, non-hormonal drugs, such as vitamins, minerals, hepatoprotectors, diuretics, enzyme drugs, immunocorrectors, adaptogens, non-steroidal anti-inflammatory drugs, herbal remedies are used. The general disadvantages of most of the remedies used today are attempts to eliminate the causes of mastopathy rather than conducting pathogenetic treatment.

THE ROLE OF INTRAUTERINE ANTIGEN EXPOSURE IN THE MORPHOGENESIS OF CEREBRAL BLOOD VESSELS

Introduction. The state of cerebral vessels in children of the first year of life with congenital toxoplasmosis, both active and without signs of activity (as models of antenatal antigenic exposure), was considered. The patients were born to mothers whose pregnancy proceeded with mild preeclampsia and perinatal damage to the nervous system. The features of the morphogenesis of the brain vessels of rats after exposure to antigens in the antenatal period were experimentally investigated. Materials and Methods. 119 children of the first year of life were examined. 43 patients with toxoplasmosis, 25 children from women whose pregnancy was complicated by mild preeclampsia, and 28 children with perinatal lesions of the nervous system of hypoxic-ischemic genesis due to antenatal hypoxia of the fetus. The comparison group consisted of 23 healthy children with an uncomplicated antenatal history. Experimental study of the morphogenesis of brain vessels of Wistar rats after intrauterine administration of antigens according to the method of M.A. Voloshin. Results. At 1–2 and 7–8 months of life, in children with antigenic antenatal exposure and perinatal lesions of the nervous system of hypoxic-ischemic genesis, blood flow disorders in the anterior cerebral arteries, vessels of the nail bed, manifestations of endothelial dysfunction and impaired function of the sympathoadrenal system were detected. In the experiment, after the intrauterine introduction of antigens of various nature, an increase in the proportion of the connective tissue component in blood vessels was established, and a significant decrease in the ratio of muscle and connective tissue components from the 1st to the 60th day of postnatal development. Changes in indicators of carbohydrate metabolism and a decrease in glycogen in the anterior cerebral artery of rats 1–60 days of life with antigenic antenatal exposure indicate long-term changes in metabolic disorders of carbohydrate metabolism in the anterior cerebral arteries. By extrapolating the results obtained in the experiment on rats, it is possible to predict metabolic disorders in the vessels of people of the appropriate age, which to a certain extent explains the ultrasound and biomicroscopic changes in vessels, endothelial dysfunction detected in children with antigenic antenatal stimulation at 1–2 and 7–8 months of life. Conclusions. The identified features indicate a change in the morphogenesis of brain vessels after antenatal antigenic exposure and are the background for the formation of central nervous system pathology in children