Laminin receptor 1 expression in premalignant and malignant squamous lesions of the cervix.

Laminin receptor 1 (LAMR) may have a role in the progression of premalignant squamous epithelial lesions to cervical cancer. Therefore, we aimed to investigate the expression of laminin receptor 1 (LAMR) in normal, premalignant, and malignant tissues of the uterine cervix. Paraffin blocks of 129 specimens with the diagnoses of normal cervical tissue (n = 33), cervical intraepithelial neoplasia (CIN) 1 (n = 30), CIN 2 (n = 14), CIN 3 (n = 28), and squamous cell carcinoma (n = 24) were immunohistochemically stained with LAMR antibody and its expression percentage, pattern, and intensity in these tissues were assessed. Compared to the other groups, the nonstaining with LAMR was highest in low grade squamous intraepithelial lesion (LSIL) (p < 0.0001). LAMR expression, which was positive in less than 50% of cells with weak staining, increased significantly between normal cervical epithelium and high-grade squamous intraepithelial lesion (HSIL) or invasive carcinoma, as well as between LSIL and HSIL (p < 0.0001). Between LSIL and invasive carcinoma, a significant increment was also observed for weak staining in less than 50% of cells (p < 0.001). LAMR expression, which was positive in more than 50% of cells with strong staining, was significantly higher in normal cervical tissue compared to the other groups (p < 0.0001). Disease progression related gradual increment of LAMR expression from normal cervical epithelium or LSIL towards HSIL or cervical cancer reveals that LAMR may play an important role in the transition from premalignant to malignant state in cervical lesions.

Histopathologic Follow-Up of Women with Inadequate ThinPrep™ Cervical Pap Tests and Positive High-Risk Human Papillomavirus Test Results.

INTRODUCTION: We found only a few studies that had performed high-risk human papillomavirus (hrHPV) analyses of inadequate ThinPrep™ Papanicolaou (Pap) tests. Therefore, this study aimed to analyze unsatisfactory ThinPrep Pap tests using hrHPV tests. The colposcopic biopsy results of cases with an unsatisfactory ThinPrep Pap test and positive hrHPV results were revealed. METHODS: Between January 1, 2018, and October 31, 2022, 965 (3.7%) of 25,958 liquid-based cytology specimens were evaluated as unsatisfactory. Ninety-five (9.8%) of 965 patients were positive for hrHPV. The colposcopic evaluation was performed in 28 (29.4%) of 95 patients, in whom 23 tests were adequate. RESULTS: Twenty-three colposcopy biopsy results showed that 17 (73.9%) of 23 patients had benign biopsy results. High-grade squamous intraepithelial lesions were observed in three (13%) of the 23 patients, and low-grade squamous intraepithelial lesions were observed in two (8.6%) of the 23 patients. One of the 23 (4.3%) patients had keratinized squamous cell carcinoma of the cervix diagnosed histologically, although no tumor was visible upon gynecologic examination. CONCLUSION: For the management of unsatisfactory Pap tests, The American Society for Colposcopy and Cervical Pathology (ASCCP) recommends repeat cytology within 2-4 months. Evaluation of such patients using hrHPV tests may triage those with squamous intraepithelial lesions, even invasive cervical cancer. More studies with a larger number of cases are needed to analyze the hrHPV status and biopsy follow-up of cases with unsatisfactory cytology.

Expression of Laminin Receptor 1 in Normal, Hyperplastic, and Malignant Endometrium.

Laminin receptor 1 may have a role in the progression from endometrial hyperplasia with or without atypia to endometrial cancer. Therefore, we aimed to investigate the pattern, percentage, and intensity of laminin receptor 1 expression in normal, hyperplastic, and neoplastic endometrium. Paraffin blocks of 131 specimens with the diagnoses of normal endometrium (n=25), endometrial hyperplasia with atypia (n=21) or without atypia (n=55), and endometrial cancer (n=30) were immunostained with laminin receptor 1 antibody, and its expression percentage, pattern, and intensity in the epithelial cytoplasm, basement membrane, and endometrial stroma of these tissues were assessed. When compared with hyperplasia with or without atypia and endometrial cancer, the percentage of nonstaining with laminin receptor 1 in the epithelial basement membrane was higher (96%), and the percentage of <50% staining with laminin receptor 1 was lower (4%) in the normal endometrium (P=0.001). While a progressive increment in staining percentage and density of epithelial cytoplasm and basement membrane was noted through an orderly progression from normal endometrium to endometrial hyperplasia without atypia, endometrial hyperplasia with atypia, and cancer of endometrium (P<0.001), such a relationship was not found for the staining percentage and density of endometrial stroma (P>0.05). Disease progression-related gradual increment in laminin receptor 1 expression in the epithelial basement membranes of hyperplastic endometrium with or without atypia and cancer of endometrium reveals that it may play a substantial role in the transition from premalignant to the malignant state of endometrial lesions.

Expression of laminin receptor 1 in human placentas from normal and preeclamptic pregnancies and its relationship with the severity of preeclampsia.

OBJECTIVES: To investigate the expression of laminin receptor 1 (LR1), a non-integrin-type laminin receptor, in preeclamptic and normal third-trimester placentas, as well as to investigate whether its expression differs with disease severity. STUDY DESIGN: Third trimester placental samples obtained from deliveries of preeclamptic (n=34) and normotensive healthy pregnant women (n=35) were immunohistochemically studied for the expression of LR1. The placentas from both mild (n=14) and severe (n=20) preeclamptic pregnancies were further assessed for strength of LR1 expression according to disease severity. RESULTS: When compared with normal placentas, the staining with LR1 protein in cytotrophoblasts and syncytiotrophoblasts was lower in preeclamptic placentas (P<0.05 and P<0.01, respectively). The intensity of staining with LR1 in decidual cells, cytotrophoblasts, syncytiotrophoblasts, and extracellular matrix cells of preeclamptic placentas did not vary with disease severity (P>0.05). CONCLUSIONS: Decreased LR1 expression in cytotrophoblasts and syncytiotrophoblasts of preeclamptic placentas, which may be independent of disease severity, might have a role in shallow trophoblastic invasion in preeclampsia.

Left ovarian gonadoblastoma with yolk sac tumor in a young woman.

Gonodoblastomas with ovarian germ cell tumors other than dysgerminoma coexists very rarely with yolk sac tumor (YST). Because of this rarity, we report a case of gonadoblastoma with YST. An 18-year-old female patient was admitted to our hospital with an abdomino-pelvic mass. Ultrasonographical examinations revealed a 15X14 cm heterogenous pelvic mass with calcific foci in the left adnexal area. Macroscopically, the resected mass was oval and measured 18X15X15 cm and weighed 3150 gm. Histological examination showed both gonadoblastic and YST areas. There were many gonadoblastic nests in the subcapsular areas of the tumor. The gonadoblastic nests were composed of large and small cells. The YST areas showed enteric differentiation and numerous hyaline globules. Immunohistochemical examination may help in the diagnosis of these gonadoblastoma with YST.

Cavernous hemangioma presenting as a giant cervical mass: a case report.

Intramuscular hemangiomas of the head and neck are rare congenital vascular tumors and are sparsely reported. Hemangiomas account for approximately 7% of benign tumors and usually present as a mass that suddenly enlarges. Hemangiomas are mostly seen on the trunk and extremities, but can also appear on the head and neck region. A10-year-old boy was referred to our clinic for puffiness and swelling on the right side of his neck. Neurological examination was normal, but we observed an advanced degree of restriction in neck movement. An MRI study showed a soft tissue mass 9 x 8 x 5 in size. The mass was totally extracted by surgical intervention and pathological analysis revealed that it was a cavernous hemangioma. The patient's neck movement returned to normal after surgery. No relapse occurred during 1-year follow-up.

A case of langerhans cell histiocytosis with anal fistula.

Langerhans cell histiocytosis (LCH) is an uncommon clinically heterogeneous disorder characterized by the proliferation and accumulation of Langerhans cells with local infiltration of tissues and organ destruction. LCH takes many clinical forms, affecting different systems and different sites in the same system with variable outcomes. Bone, skin, lymph node, pituitary, liver, lung, bone marrow and spleen involvement can be seen in patients with LCH. Involvement of the perianal site is rare. In this article, a 16-month-old boy with multiple organ involvement including skin, liver, lung, and bone is presented. Aside from these systemic involvements, he also had a simple anal fistula. According to our best knowledge, this case of LCH with anal fistula is only the second to be reported in childhood. We would like to emphasize that LCH may be associated with anal fistula; therefore, we suggest that patients with LCH should be examined for this condition.

Protective effect of sildenafil (Viagra) in transient spinal cord ischemia.

Prospective study of the neuroprotective activity of sildenafil in a rat spinal ischemia model. The present study involved 21 male Sprague-Dawley rats. The animals were divided into 3 groups. Physiological serum was administered intraperitoneally to the 8 rats in the control group at the beginning of reperfusion for a period of 20 min after abdominal aortal occlusion. Sildenafil (Viagra) was administered as a single 10-mg/kg/day intraperitoneal dose to the 8 rats in the sildenafil group at the beginning of reperfusion after 20 min of abdominal aortal occlusion. No occlusion was performed and no agent was administered to the 5 rats in the sham group, but the abdominal aorta was reached by means of surgical intervention. Before the animals were sacrificed, several physiological and biochemical parameters were investigated, preoperative and postoperative motor functions were also assessed, and somatosensory evoked potential (SEP) monitoring and histopathological examinations were carried out. No differences were found between the physiological and biochemical parameters in each of the 3 groups. Neurological scoring performed after reperfusion demonstrated a significant improvement in the neurological results relative to those of the control group over 48 h in subjects that received sildenafil. These animals also showed better 24-hour SEP results, measured in terms of extended latency and decreased amplitude, than the control animals. A histopathological study showed reduced ischemic symptoms in rats that received sildenafil compared with those in the control group. However, no anomalies were observed in the sham group with respect to the histopathological and neurological findings. These results indicate that neurological damage due to spinal-cord ischemia-reperfusion injury can be reduced by sildenafil.

Attenuation of bleomycin-induced lung fibrosis by oral sulfhydryl containing antioxidants in rats: erdosteine and N-acetylcysteine.

Antioxidant therapy may be useful in diseases with impaired oxidant antioxidant balance such as lung fibrosis. The effects of sulfhydryl-containing antioxidant agents N-acetylcysteine (NAC) and erdosteine on the bleomycin-induced lung fibrosis were compared in rats. The animals were divided into four groups: Vehicle + vehicle, vehicle + bleomycin (2.5 U/kg), bleomycin + (10 mg/kg), and bleomycin + NAC (3 mmol/kg). Bleomycin administration resulted in prominent lung fibrosis as measured by lung hydroxyproline content and lung histology which is almost completely prevented by erdosteine and NAC. Hydroxyproline content was 18.7 +/- 3.5 and 11.2 +/- 0.6 mg/g dried tissue in bleomycin and saline treated rats, respectively (P < 0.001), and this level was 11.3 +/- 1.2 and 13.8 +/- 1.2 mg/g dried tissue in erdosteine and NAC pretreated, respectively. Erdosteine and NAC significantly reduced depletion of glutathione peroxidase, and prevented increases in myeloperoxidase activities, nitric oxide, and malondialdehyde levels in lung tissue produced by bleomycin. Data presented here indicate that erdosteine and NAC similarly prevented bleomycin-induced lung fibrosis and their antioxidant effects were also similar in this experiment.

Effects of aminoguanidine and antioxidant erdosteine on bleomycin-induced lung fibrosis in rats.

Reactive oxygen and nitrogen species have been implicated in the pathogenesis of bleomycin-induced lung fibrosis. The effects of aminoguanidine and erdosteine on the bleomycin-induced lung fibrosis were evaluated in rats. The animals were placed into five groups: Vehicle + vehicle, vehicle + bleomycin (2.5 U/kg), bleomycin + aminoguanidine (200 mg/kg), bleomycin + erdosteine (10 mg/kg), and bleomycin + erdosteine + aminoguanidine. Bleomycin administration resulted in prominent lung fibrosis as measured by lung hydroxyproline content and lung histology, which is completely prevented by erdosteine and aminoguanidine. A strong staining for nitro tyrosine antibody in lung tissue and increased levels of lung NO were found in bleomycin group, that were significantly reduced by aminoguanidine and erdosteine. Aminoguanidine and erdosteine significantly prevented depletion of superoxide dismutase and glutathione peroxidase and elevated myeloperoxidase activities, malondialdehyde level in lung tissue produced by bleomycin. Data presented here indicate that aminoguanidine and erdosteine prevented bleomycin-induced lung fibrosis and that nitric oxide mediated tyrosine nitration of proteins plays a significant role in the pathogenesis of bleomycin-induced lung fibrosis. Also our data suggest that antifibrotic affect of antioxidants may be due to their inhibitory effect on nitric oxide generation in this model.

Erdosteine prevents bleomycin-induced pulmonary fibrosis in rats.

Oxidative stress plays an important role in the pathogenesis of idiopathic pulmonary fibrosis. Therefore, erdosteine, an antioxidant, is expected to have an inhibitor potential against the disease. Rats were given one dose of bleomycin in pulmonary fibrosis groups and saline in controls. The first dose of oral erdosteine (10 mg/kg/day) was given 2 days before the bleomycin injection to achieve the plateau level in blood and continued until killing. At day 14, fibrotic changes were evaluated, using Aschoft's criteria and lung hydroxyproline content. Bleomycin produced a fivefold increase in fibrosis score that was decreased by 87% by erdosteine (P>0.001) and almost twofold increases in hydroxyproline content which were completely prevented by erdosteine. Myeloperoxidase activities and MDA levels, which were significantly higher in the bleomycin group, were then significantly attenuated by erdosteine. These results revealed that oral erdosteine may prevent the development of acute pulmonary inflammation caused by bleomycin injection via the repression of neutrophil accumulation and lipid peroxidation, resulting in the inhibition of subsequent lung fibrosis.

Monostotic fibrous dysplasia originating from ethmoid bone: treatment with endoscopic approach.

We present a case of monostotic fibrous dysplasia of the ethmoidal sinus in an 11-year-old boy. This condition is of interest to the otorhinolaryngologist because of the difficulty of differential diagnosis and treatment. This tumorlike growth was not restricted to the right ethmoidal sinus, but also compressed the orbit and the globe. Endoscopic and transnasal removal of the mass with a drill was performed under general anesthesia. No residual tumor was observed 6 months later.

Role of caffeic acid phenethyl ester, an active component of propolis, against cisplatin-induced nephrotoxicity in rats.

We have investigated the effect of caffeic acid phenethyl ester (CAPE) on cisplatin-induced nephrotoxicity in rats. Administration of a single dose of cisplatin resulted in the elevation of blood urea nitrogen and creatinine in serum, as well as nitric oxide in kidney tissue of rats. Cisplatin also caused reduction of catalase (P < 0.0001), superoxide dismutase (P = 0.149) and glutathrone peroxidase (P < 0.0001) activities in kidney tissue. Although cisplatin caused elevation in malondialdehyde levels and myeloperoxidase activities in kidney tissue, they were not statistically significant. Caffeic acid phenethyl ester was found to be protective against cisplatin-induced antioxidant enzyme reductions. Treatment with free-radical scavenger CAPE attenuated the increase in plasma blood urea nitrogen and kidney nitric oxide levels, and showed histopathological protection against cisplatin-induced acute renal failure. Extensive epithelial cell vacuolization, swelling, desquamation and necrosis were observed in the kidney of the cisplatin-treated rat. There were also larger tubular lumens in cisplatin-treated rats than those of the control and the CAPE groups. Caffeic acid phenethyl ester caused a marked reduction in the extent of tubular damage. It is concluded that administration of cisplatin imposes an oxidative stress to renal tissue and CAPE confers protection against the oxidative damage associated with cisplatin. This mechanism may be attributed to its free-oxygen-radical scavenging activity.

Ginkgo biloba prevents mobile phone-induced oxidative stress in rat brain.

BACKGROUND: The widespread use of mobile phones (MP) in recent years has raised the research activities in many countries to determine the consequences of exposure to the low-intensity electromagnetic radiation (EMR) of mobile phones. Since several experimental studies suggest a role of reactive oxygen species (ROS) in EMR-induced oxidative damage in tissues, in this study, we investigated the effect of Ginkgo biloba (Gb) on MP-induced oxidative damage in brain tissue of rats. METHODS: Rats (EMR+) were exposed to 900 MHz EMR from MP for 7 days (1 h/day). In the EMR+Gb groups, rats were exposed to EMR and pretreated with Gb. Control and Gb-administrated groups were produced by turning off the mobile phone while the animals were in the same exposure conditions. Subsequently, oxidative stress markers and pathological changes in brain tissue were examined for each groups. RESULTS: Oxidative damage was evident by the: (i) increase in malondialdehyde (MDA) and nitric oxide (NO) levels in brain tissue, (ii) decrease in brain superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities and (iii) increase in brain xanthine oxidase (XO) and adenosine deaminase (ADA) activities. These alterations were prevented by Gb treatment. Furthermore, Gb prevented the MP-induced cellular injury in brain tissue histopathologically. CONCLUSION: Reactive oxygen species may play a role in the mechanism that has been proposed to explain the biological side effects of MP, and Gb prevents the MP-induced oxidative stress to preserve antioxidant enzymes activity in brain tissue.

Inhibitory effect of caffeic acid phenethyl ester on bleomycine-induced lung fibrosis in rats.

BACKGROUND: Pulmonary fibrosis (PF) induced by anticancerogenic bleomycin (BLM) is one of the more common side effects encountered during cancer treatment. It has been suggested in the last decades that the main responsible agent in PF is reactive oxygen species which were generated also in normal physiological conditions in the human body. In this experimental study, we investigated the preventive or attenuating effects of caffeic acid phenethyl ester (CAPE) that has been demonstrated to have anti-inflammatory, cytocytatic, anticancerogenic, antiprolipherative and antioxidant effects on BLM-induced PF. METHODS: Thirty-six Sprague-Dawley rats were divided randomly into four groups as sham operation, BLM, BLM + vitamin E (vit E), and BLM + CAPE groups. BLM (7.5 mg/kg, single dose) was applied intratracheally, and CAPE and vit E intraperitoneally in the appropriate groups. At the end of the fibrosis processes, lung tissues were removed and the levels of tissues hydroxyproline (OH-proline), malondialdehyde (MDA) and NO as well as the activities of superoxide dismutase (SOD), catalase (CAT) and myeloperoxidase (MPO) were determined. Also, the weights of the rats were recorded at 7th and 14th days of the experiments. RESULTS: BLM application to the rats resulted in a significant increase in the OH-proline level as compared to the controls. Administration of CAPE and vit E led to the remarkable reduction of total lung OH-proline levels compared to the rats treated with BLM alone (p < 0.0001). There were a decreases in antioxidant enzyme (SOD and CAT) activities while an increase in MPO activity in BLM group was found vs. the control group (p < 0.0001). CAPE had a regulator effect on these parameters: the increase in CAT and SOD activities and the decrease in MPO activity were seen after CAPE application. NO, MDA and OH-proline levels were increased in BLM group vs. the control group. CAPE was more effective in decreasing the tissue levels of NO, MDA and OH-proline than vit E. MPO activity, as a good marker of neutrophil sequestration to the tissues, in the BLM group was decreased by CAPE approximately to the control group. CONCLUSION: We suggest that CAPE is more effective on the prevention of BLM-induced fibrosis via antioxidant and free radical scavenger properties than vit E at the doses used in the present study. CAPE has some attenuating effects on BLM-induced PF affecting both oxidant and antioxidant systems as well as neutrophils sequestration.

Colchicine-induced myopathy in a teenager with familial Mediterranean fever.

OBJECTIVE: To report a case of colchicine-induced myopathy in a teenager with familial Mediterranean fever (FMF). CASE SUMMARY: A 15-year-old boy of Turkish origin, diagnosed as having FMF at the age of 14 years, was treated with colchicine 1.5 mg/d. He had experienced only 2 mild peritonitis attacks with fever within 1 year. The patient used the recommended dose regularly, and he described progressive proximal muscle weakness and generalized myalgias, which started 1 month before presentation. Physical examination showed proximal muscle weakness in his arms and legs. Laboratory tests revealed elevated serum creatine kinase, aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase. All other laboratory values were within normal range. Electromyographic investigation revealed a myopathic pattern in proximal muscles without any neuropathic changes. A biopsy of the deltoid muscle showed vacuolar degeneration of striated muscle fibers with no inflammatory findings. DISCUSSION: Colchicine, the most important drug in treatment of FMF, can cause myopathy in patients with impaired renal and hepatic function. In our patient, an objective causality scale showed that therapeutic doses of colchicine for FMF were the definite cause of myopathy, even though his renal and hepatic function were normal. The treatment of FMF attacks in patients who cannot use colchicine is an important problem. There are insufficient data about the use of immunosuppressive agents in the treatment of FMF attacks; however, we now successfully control the attacks with colchicine 0.5 mg/d and azathioprine 2 mg/kg/d. CONCLUSIONS: Colchicine-induced myopathy should be excluded in patients with FMF who present with generalized muscle weakness. Clinicians should be aware that myopathy can occur in patients with FMF who have normal renal and hepatic function.