ABSTRACT
Ischaemic post-conditioning (IPostC) might represent an innovative surgical approach to protect organs from ischaemia and reperfusion (I/R) injury. We investigated the molecular mechanisms underlying the contrasting effects of IPostC on the early and late damage induced by testicular I/R injury. Testis I/R was induced by occluding the right testicular vessels using a clip. Male rats were divided into the following groups: sham, I/R and I/R + IPostC. In the I/R group, the clip was removed after 60 min of ischaemia, and reperfusion was allowed for 30 min, 1 and 30 days. In the I/R + IPostC group, three cycles of 30-sec reperfusion and 30-sec ischaemia were performed after 60 min of ischaemia and then reperfusion followed up for 30 min, 1 and 30 days. Following 30-min reperfusion, there was an increase in mitogen-activated protein kinases (MAPKs) in I/R rats; after 1 day of reperfusion, interleukin-6, tumour necrosis factor-α and nuclear factor-κB (NF-κB) expression were significantly increased; IκB-α expression reduced; and a marked damage in both testes was observed. IPostC inhibited MAPKs, cytokines and NF-κB expression, augmented IκB-α expression and decreased histological damage in testes subjected to I/R. After 30 days of reperfusion, I/R injury activated the apoptosis machinery, caused severe histological damage and reduced spermatogenic activity. By contrast, IPostC did not modify the apoptotic markers, the histological alterations as well as spermatogenic activity following 30 days of reperfusion. Our data demonstrate that IPostC protects the testis from the early damage induced by I/R injury, but it does not protect against the late damage.
Subject(s)
Ischemic Postconditioning , Reperfusion Injury/pathology , Spermatic Cord Torsion/pathology , Testis/injuries , Animals , Apoptosis , I-kappa B Proteins/biosynthesis , Interleukin-6/biosynthesis , Male , Mitogen-Activated Protein Kinases/biosynthesis , NF-KappaB Inhibitor alpha , NF-kappa B/antagonists & inhibitors , NF-kappa B/biosynthesis , Rats , Rats, Sprague-Dawley , Spermatogenesis , Tumor Necrosis Factor-alpha/biosynthesisABSTRACT
The effects of polydeoxyribonucleotide (PDRN), an agonist of the A2A adenosine receptors which when activated positively influences sperm activity, were tested in an experimental testicular ischaemia/reperfusion injury model. Anaesthetized male Sprague-Dawley rats were subjected to testicular torsion-induced ischaemia, followed by reperfusion (TI/R). Immediately after detorsion, randomized animals, including SHAM, received intraperitoneal injections of: (i) vehicle (1 mL/kg 0.9% NaCl solution); (ii) PDRN (8 mg/kg); (iii) DMPX (3,7-dimethyl-1-propargilxanthine, 0.1 mg/kg); or (iv) PDRN (8 mg/kg) + DMPX (0.1 mg/kg). Animals were euthanized at 1, 7 and 30 days following reperfusion. Vascular endothelial growth factor (VEGF) expression is normally associated with adenosine A2A receptor stimulation. After treatment, VEGF mRNA/protein expression quantified by qPCR and Western blot, vascular endothelial growth factor receptor-1 (VEGFR1) and endothelial nitric oxide synthase (eNOS) mRNA measured by qPCR, VEGF and VEGFR1 assessed using immunohistochemical methods, histological staining and spermatogenic activity were all analysed. Testis ischaemia-reperfusion (TI/R) injury caused increases in VEGF mRNA and protein, VEGFR1 and eNOS mRNA, histological damage and reduced spermatogenic activity. Immunostaining showed a lower expression of VEGF in germinal epithelial cells and a strong expression of VEGFR1 in Leydig cells after TI/R. PDRN administration increased significantly VEGF message/protein, VEGFR1 and eNOS message, decreased histological damage and ameliorated spermatogenic activity. PDRN might be useful in the management of testicular torsion.
Subject(s)
Adenosine A2 Receptor Agonists/pharmacology , Polydeoxyribonucleotides/pharmacology , Reperfusion Injury/drug therapy , Spermatic Cord Torsion/drug therapy , Spermatogenesis/drug effects , Testis/blood supply , Animals , Immunohistochemistry , Leydig Cells/metabolism , Male , Nitric Oxide Synthase Type III/genetics , Nitric Oxide Synthase Type III/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , Random Allocation , Rats , Rats, Sprague-Dawley , Reperfusion Injury/metabolism , Reperfusion Injury/pathology , Spermatic Cord Torsion/metabolism , Spermatic Cord Torsion/pathology , Testis/drug effects , Testis/pathology , Vascular Endothelial Growth Factor A/genetics , Vascular Endothelial Growth Factor A/metabolism , Vascular Endothelial Growth Factor Receptor-1/biosynthesis , Vascular Endothelial Growth Factor Receptor-1/genetics , Vascular Endothelial Growth Factor Receptor-1/metabolismABSTRACT
Aquaporin-9 (AQP-9) regulates tissue hydration by promoting transmembrane exchanges of both water and solutes, such as lactate. The latter is a key metabolite of primary spermatocytes and of maturing haploid germ cells (h-GCs). The present investigation was aimed at immunolocalising human AQP-9 in both normal and varicocele testes. Histology and immmunocytochemistry were investigated in archival biopsies from 20 varicocele testes and in eight unaffected ones. AQP-9 immunostaining was performed using a rabbit antibody, and either focal or diffuse cell membrane labelling was recorded. Varicocele testes showed disarranged tubular compartments, with sloughing h-GCs, tissue hyperhydration, spermiogenesis failure and fibrosis. AQP-9 immunohistology of the control testes showed a diffuse cell membrane staining of the primary spermatocytes and h-GCs, without any positive reaction of spermatogonia and Sertoli cells. AQP-9 cell expression in the varicocele testes was focal or lacking in both adluminal and sloughing GCs. AQP-9 expression occurs in normal human testis, at cell membrane of primary spermatocytes and h-GCs, suggesting a possible role of AQP-9 in the water and lactate transport from Sertoli cells to GCs. AQP-9 is focal or lacking in adolescent varicocele testes, and this suggests AQP-9 to be downregulated in such testicular disorder, leading to lactate deprivation with subsequent hypospermatogenesis.
Subject(s)
Aquaporins/metabolism , Cell Hypoxia/physiology , Spermatocytes/metabolism , Spermatogenesis/physiology , Testis/metabolism , Varicocele/metabolism , Adolescent , Biopsy , Case-Control Studies , Cell Membrane/metabolism , Extracellular Matrix/metabolism , Humans , Male , Sertoli Cells/metabolism , Sertoli Cells/pathology , Spermatids/metabolism , Spermatids/pathology , Spermatocytes/pathology , Spermatozoa/metabolism , Spermatozoa/pathology , Testis/pathology , Varicocele/pathologySubject(s)
Testis/abnormalities , Child , Humans , Immunohistochemistry , Male , Sertoli Cells/pathology , Testis/pathologyABSTRACT
BACKGROUND: Aberrant Wingless type 1 glycoprotein (Wnt) pathway in ameloblastomas and a role of syndecan-1 (SDC1) in activating Wnt signalling were perspected. SDC1 shifting from epithelium to stroma was reported in invasive non-odontogenic neoplasms. The aim of this study was to reveal the role of SDC1 and Wnt1 in intraosseous ameloblastomas (IA(s)). METHODS: SDC1 and Wnt1 expressions were investigated in 29 ameloblastoma subtypes and seven tooth buds. RESULTS: SDC1 immunostaining strongly depicted stromal cells, extracellular matrix (ECM) and basement membranes of ameloblastomas. It also showed epithelial tumour cells in the acanthomatous and plexiform subtypes, and it often occurred in stellate reticulum cells and basal ameloblasts of tooth buds. Parallel Wnt1 expression occurred in ameloblastomatous epithelial cells, but it was common in basal cells of tooth buds too. Statistically, a significant correlation was found between the percentage of IA(s)-bearing SDC1-positive stromal cells and ECM and the percentage of IA(s)-bearing Wnt1-positive epithelial cells. CONCLUSIONS: A role of SDC1 in stromal cells and ECM can be hypothesized as a critical factor for carcinogenesis and local invasiveness of IA(s).
Subject(s)
Ameloblastoma/pathology , Syndecan-1/analysis , Wnt1 Protein/analysis , Ameloblastoma/classification , Ameloblasts/pathology , Basement Membrane/pathology , Cytoplasm/ultrastructure , Dental Enamel/pathology , Epithelial Cells/pathology , Extracellular Matrix/chemistry , Humans , Signal Transduction/physiology , Stromal Cells/pathology , Tooth Germ/pathologyABSTRACT
OBJECTIVES: Recent reports showed an altered density of interstitial cells of Cajal (ICCs) and of peripherin immunoreactive nerve fibres in obstructed uretero-pelvic junction. Our aim was to investigate ICCs immunoexpression and ureteral innervation in primary obstructive megaureter (POM). METHODS: 8 specimens of POM were obtained during tailoring. Restricted segments of ureters were divided from the dilated ones. C-kit and peripherin immunohistochemistry were performed. RESULTS: A normal distribution of ICCs was documented in both circular and longitudinal muscular layers of dilated segments. Marked muscular hypoplasia and a sparse or absent ICCs occurred in longitudinal muscular layer of restricted ureteral segments. A normal distribution of peripherin positive fibres was present in both dilated and restricted segments. CONCLUSIONS: Our data confirmed a defective muscolarization in restricted, aperistaltic POM. The lacking of ICCs in the longitudinal muscular layer is, probably, due to the absence of c-kit positive muscular embryological precursors. No alteration of peripherin immunoreactive nerve fibres network was observed in both dilated and restricted ureteral segments.
Subject(s)
Coiled Bodies/immunology , Coiled Bodies/pathology , Ureteral Obstruction , Female , Humans , Immunohistochemistry , Infant , Male , Muscle, Smooth/immunology , Muscle, Smooth/innervation , Muscle, Smooth/pathology , Nerve Fibers/immunology , Proto-Oncogene Proteins c-kit/immunology , Ureteral Obstruction/immunology , Ureteral Obstruction/pathology , Ureteral Obstruction/physiopathologyABSTRACT
AIM: Recent reports have shown an altered density of interstitial cells of Cajal (ICCs) and peripherin immunoreactive nerve fibres in uretopelvic junction obstruction. The aim was to investigate ICCs immunoexpression and ureteral innervation in primary obstructive megaureter (POM). METHODS: Eight specimens of POM were obtained during tailoring. Restricted segments of ureters were divided from dilated segments. C-kit and peripherin immunohistochemistry were performed. RESULTS: A normal distribution of ICCs was observed in both the circular and longitudinal muscle layers of the dilated segments. Marked muscle hypoplasia and sparse or no ICCs occurred in the longitudinal muscle layer of the restricted ureteral segments. A normal distribution of peripherin positive fibres was present in both the dilated and restricted segments. CONCLUSIONS: Our data confirm defective muscularization in restricted aperistaltic POM. The lack of ICCs in the longitudinal muscular layer is probably due to the absence of c-kit positive muscle embryological precursors. No alteration in the peripherin immunoreactive nerve fibres network was observed in either the dilated or the restricted ureteral segments.
Subject(s)
Coiled Bodies/metabolism , Intermediate Filament Proteins/metabolism , Muscle, Smooth/pathology , Proto-Oncogene Proteins c-kit/metabolism , Ureteral Obstruction/metabolism , Ureteral Obstruction/pathology , Female , Humans , Infant , Male , Muscle, Smooth/metabolism , Nerve Fibers/pathology , Nerve Tissue Proteins/metabolismABSTRACT
Endometrial polypoid adenomyomatosis in an 8-year-old German shepherd bitch is described. The lesion was associated with ovarian granulosa cell tumour and pyometra; grossly, it consisted of sessile or pedunculated processes with both epithelial and non-epithelial components, in which smooth muscle cells were predominant. The endometrium was diffusely atrophic and showed multifocal squamous metaplasia. The findings are discussed as possible consequences of the functioning ovarian tumour and pyometra, but an involvement of growth factors is also proposed.
Subject(s)
Adenomyoma/veterinary , Dog Diseases/pathology , Granulosa Cell Tumor/veterinary , Ovarian Neoplasms/veterinary , Polyploidy , Uterine Diseases/veterinary , Adenomyoma/pathology , Animals , Dogs , Endometrial Neoplasms/pathology , Female , Granulosa Cell Tumor/pathology , Ovarian Neoplasms/pathology , Uterine Diseases/pathologyABSTRACT
Inflammatory myofibroblastic tumor (IMT) of the ileum is a rare, usually solitary lesion, that frequently presents small-intestinal intussusception and obstruction. We describe an IMT of the ileum in a 4.5-year old child who presented a small bowel intussusception. During laparotomy, an annular mass around the ileum was resected, and the IMT was histologically diagnosed. Three months after the operation, the patients were hospitalized with the symptoms of intestinal obstruction. Laparotomy showed a ileal intussusception. Along the previous suture line of anastomosis, a smooth polypoid tumor was evident. Segmental resection of the ileum, including the tumor mass, was performed. The IMT was immunohistochemically diagnosed. The patient was asymptomatic at 3 year follow-up. A review of the literature for this rare entity emphasizes the importance of immunohistochemical confirmation of its benign nature. Because of the risk of local recurrence, IMT cases should have a long-term follow-up.
Subject(s)
Ileal Diseases/etiology , Ileal Neoplasms/complications , Intussusception/etiology , Neoplasm Recurrence, Local/complications , Child, Preschool , Humans , Ileal Neoplasms/surgery , MaleABSTRACT
Vaginal submucosal nodules were observed in a 67-year-old woman, with ultrasonographic features of an advanced uterine neoplasm. On biopsy, light microscopy suggested that the lesions might be metastatic foci from an extragenital cancer, with a prevalent tubular growth pattern. Parallel immunohistochemical reactions revealed a diffuse, strong CA 19-9 positivity in both the cell membrane and cytoplasm. Subsequently, high serum levels of such tumor marker were also found, and an extragenital cancer was suspected of pancreatic or biliary origin. A mass in the gallbladder fossa was then detected by computed tomography and a primary gallbladder adenocarcinoma was confirmed on ultrasound-guided biopsy.
Subject(s)
Adenocarcinoma/diagnosis , Gallbladder Neoplasms/diagnosis , Uterine Neoplasms/diagnosis , Vaginal Neoplasms/diagnosis , Adenocarcinoma/complications , Adenocarcinoma/secondary , Aged , Diagnosis, Differential , Fatal Outcome , Female , Gallbladder Neoplasms/pathology , Humans , Neoplasm Metastasis , Postmenopause , Uterine Hemorrhage/etiology , Uterine Neoplasms/complications , Uterine Neoplasms/secondary , Vaginal Neoplasms/secondarySubject(s)
Abdominal Neoplasms/secondary , Dog Diseases/pathology , Granulosa Cell Tumor/secondary , Testicular Neoplasms/veterinary , Abdominal Neoplasms/surgery , Animals , Dog Diseases/surgery , Dogs , Fatal Outcome , Granulosa Cell Tumor/pathology , Granulosa Cell Tumor/surgery , Granulosa Cell Tumor/veterinary , Male , Testicular Neoplasms/pathology , Testicular Neoplasms/surgeryABSTRACT
PURPOSE OF INVESTIGATION: Retrospective evaluation of hysteroscopic findings in the accurate diagnosis of endometrial carcinoma. METHODS: A retrospective monocentric study from January 1995 to December 2004. One hundred and four patients with hysteroscopic aspects evocative of endometrial carcinoma confirmed by endometrial biopsy during diagnostic hysteroscopy, by surgical hysteroscopic resection pieces or by hysterectomy specimen were included. RESULTS: Among the 104 patients, diagnostic hysteroscopy pointed out endometrial features suggestive of endometrial carcinoma in 102 cases. In two women diagnostic hysteroscopy failed to diagnose endometrial malignancy which was identified on pieces of polyps by surgical hysteroscopic resection. DISCUSSION: Polypoid proliferations cerebroid in appearance, with ulceration and necrosis, friable and with irregular vessels, represent endometrial findings highly indicative of malignancy. The diagnosis may be missed in cases of focal neoplasias, within endometrial polyps or in conditions of unsatisfactory endouterine visualization.
Subject(s)
Endometrial Neoplasms/diagnosis , Hysteroscopy , Aged , Aged, 80 and over , Female , Humans , Middle Aged , Retrospective StudiesABSTRACT
OBJECTIVES: To investigate the immunoexpression of aquaporin-1 (AQP-1), a major transmembrane water channel, in high-grade varicocele testes, which are known to imply an unbalanced transmembrane water flow, in both tubular and extratubular compartments. METHODS: Light microscopy and AQP-1 immunohistologic examination were carried out on incisional testicular biopsies from 20 adolescent boys, aged 13 to 18 years, with grade 2 or 3 idiopathic varicocele. Testicular tissue from 4 autopsied subjects of matched age were also investigated as parallel controls. RESULTS: At microscopic examination, the tubular lumina and extracellular matrix were expanded and venular profiles dilated. Cytoplasmic vacuoles were frequent in the Sertoli cells, spermatogonia, and spermatocytes, together with premature sloughing of germ cells and residual cytoplasmic droplets inside the spermatozoa, if present. Diffuse AQP-1 positivity occurred at venular endothelial cell membranes and, unexpectedly, at the cell membranes of the Sertoli cells, diploid germ cells, and haploid cells. In the control testes, focal AQP-1 immunolabeling was confined to the microvessel endothelial cells, without any positive reaction in the tubular or extratubular compartments. CONCLUSIONS: This is the first report showing AQP-1 cell expression in adolescent varicocele testes in both tubular and extratubular compartments. It was associated with the main histologic features of unbalanced water flow in the tubular and interstitial compartments of the testis. Immunocytochemical patterns revealed AQP-1 as a possible critical reabsorption factor, acting to reduce abnormal fluid retention in endotubular cells and the extracellular matrix and, to a lesser extent, in Leydig cells.
Subject(s)
Aquaporins/analysis , Testis/chemistry , Varicocele/metabolism , Absorption , Adolescent , Aquaporin 1 , Aquaporins/physiology , Blood Group Antigens , Body Fluids/metabolism , Body Water/metabolism , Endothelial Cells/chemistry , Extracellular Matrix/metabolism , Humans , Immunoenzyme Techniques , Leydig Cells/metabolism , Male , Seminiferous Tubules/chemistry , Testis/pathology , Varicocele/pathologyABSTRACT
OBJECTIVES: The aim of this study was to demonstrate the ultrasonographic features of prenatal bilateral torsion of the testis, and its histological correlation and management. PATIENT: A newborn presented at delivery with both testes enlarged, swollen and tender. Prenatal ultrasound (US) showed enlarged, hyperechoic testes. Colour Doppler US examination was performed. RESULTS: US revealed both testes to be heterogeneous. Colour Doppler US did not reveal any flow signal. On inguinal exploration both testes appeared necrotic. Histology showed recognizable seminiferous tubules and Leydig cells. CONCLUSION: We believe that both testes should be left in situ after bilateral detorsion even if their macroscopic appearance is necrotic.
ABSTRACT
The authors are interested in determining causes of gallbladder cancer (GBC). By this intention, they theorize a correlation between genetic modifications (which are responsible of malignant transformation of biliary epithelium) and some intestinal infections. From 1999 to 2004 they observed 15 GBC and all 15 gallbladder have been analyzed histologically and from microbiological aspect; by these means from 1999 till 2004 they have studied also 30 persons with colelithiasis. The authors noticed that bile of both groups contained, in three cases in the first and in 8 cases in the second, a germ named Escherichia Coli which normally lives in intestine, while in 10 operated gallbladders of the first group and 12 of the second there was a positive for k-ras. They are studying to confirm their theories.
Subject(s)
Gallbladder Neoplasms/etiology , Aged , Female , Humans , Male , Middle AgedABSTRACT
A 30-year-old Standardbred stallion was examined for unilateral scrotal swelling. Physical and ultrasound examinations revealed a painless enlarged left testis with a non-homogeneous echogenicity, when compared with the controlateral testis. The stallion underwent left unilateral orchiectomy. Grossly, the excised testis was irregularly enlarged (12 x 9 x 9 cm; weight: 530 g) and firm. The sections showed that testicular parenchyma was replaced by a lobulated, greyish-white mass, which involved the epididymal head. At microscopy, a dual Leydig and Sertoli cell tumour component could be seen. Neoplastic Sertoli cells were prevalent and presented pleomorphic cells, mitotic figures and occasional vascular invasion. Tumour patterns showed tubular and solid areas, cord-like or diffuse in appearance, among which newly formed Leydig cell nests and low-density fibrillar bundles were interposed. Immunohistochemically, a weak to moderate immunostaining for vimentin, AE(1)/AE(3) cytokeratin, alpha-1-antitrypsin and CD99 antigens was found in the growing Sertoli cells, whose nuclear MIB-1 labelling index scored 13 +/- 2%. The Leydig tumour cells, on the other hand, displayed a moderate to strong positivity for alpha-inhibin, vimentin, AE(1)/AE(3) cytokeratin, neurone-specific enolase and CD99. On the basis of these findings, a diagnosis of malignant mixed sex cord-stromal tumour was made.
Subject(s)
Horse Diseases/pathology , Sex Cord-Gonadal Stromal Tumors/veterinary , Testicular Neoplasms/veterinary , Animals , Horse Diseases/surgery , Horses , Immunohistochemistry/veterinary , Leydig Cells/pathology , Male , Orchiectomy/veterinary , Sertoli Cells/pathology , Sex Cord-Gonadal Stromal Tumors/pathology , Sex Cord-Gonadal Stromal Tumors/surgery , Testicular Neoplasms/pathology , Testicular Neoplasms/surgeryABSTRACT
OBJECTIVE: A case of Stage IIA primary ovarian leiomyosarcoma (LMS) with an unfavorable outcome 24 months after total abdominal hysterectomy with bilateral salpingo-oophorectomy, despite chemotherapy treatment, is described. Eighteen months from surgery the patient showed peritoneal spreading with ascites, liver and lung metastases. The present study was aimed to compare tumor growth fraction with cell density, lesion stage and clinical course. METHODS: The surgical specimens were evaluated by histological, histochemical, and immunocytochemical methods. Under microscopy, mitotic index (MI) was estimated, as a ratio of mitotic figures per 1000 tumor cells. Immunohistology was also carried out to reveal some intermediate-type filamentous proteins, as histogenetic markers, and the MIB1 monoclonal antibody was used to assess the percent of MIB1-positive nuclei (MIB1 labeling index). RESULTS: The histologic findings and immunohistology of the assayed intermediate filamentous proteins substantiated a diagnosis of LMS, with associated coagulation necrosis and not rare mitotic figures. A dual tumor component was observed, representing both the pleomorphic and myxoid LMS-variants. On the basis of the quantitative findings, a MI of 10.9 and a MIB1-LI of 23.1 were calculated, on average. CONCLUSIONS: The proliferation indices in the described variant of ovarian LMS, denote a fast growing malignancy. They agree with the tumor stage at operation and the subsequent fatal outcome.