The protective effect of the proteasome inhibitor bortezomib on the uterus of ovariectomized rats.

Bortezomib (BORT) is an anti-tumour agent that inhibits proteasome, which is responsible for the degradation of many intracellular proteins. Although some side-effects and chemotherapeutic effects of BORT are known, there has not been enough research regarding its effects on different tissues of proteasome inhibition in the senile period (post-menopausal). The aim of this study was to investigate the safety of using BORT during the post-menopausal period. The post-menopausal effects of BORT were investigated on ovariectomized (OVX) Spraque-Dawley rats. The female rats were separated into three groups: control, ovariectomized (OVX), and OVX + BORT. OVX and OVX + BORT groups consisted of six rats in each. BORT was administered intraperitoneally in a dosage of 0.2 mg/kg two days a week for four weeks after OVX. The uteri of the rats were investigated using morphometrical, histopathological, and immunohistopathological methods. A striking atrophy in the endometrium and myometrium was observed due to an estrogen deficiency in the OVX group. The partial protective effect of BORT administration was observed morphometrically and histopathologically. In immunohistochemical research, cytoplasmic NF-KB activity was observed in the presence of proteasome inhibition in the endometrium. In light of these findings, the limited protective effects of post-menopausal BORT administration are worth mentioning.

Endometriosis in the Bartholin gland.

A case of endometriosis infiltrating the Bartholin gland is presented. The initial diagnosis was a Bartholin gland cyst. The clinical diagnosis was made during the operation when chocolate-colored fluid poured into operation field. Laparoscopy was done during the same operation and minimal endometriosis was found. The presence of endometriosis may be considered as a diagnosis in cases with cystic mass in the Bartholin gland and laparoscopy might be performed to rule out the presence of intraperitoneal endometriosis if a woman is infertile.

The significance of immunohistochemistry in the skin pathergy reaction of patients with Behçet's syndrome.

BACKGROUND: Behçet's syndrome is a chronic systemic immuno-inflammatory disorder affecting multiple organs with generalized vasculitis of arteries and veins. Although the aetiology is still unknown, endothelial dysfunction is one of the most prominent features in Behçet's syndrome. The skin pathergy reaction (SPR) is a non-specific hyperreactive lesion formation that is one of the major features and diagnostic criteria of the disease. It develops after 24-48 h at the site of the needle-prick, especially in the exacerbation period, and it is very similar to the erythematous papules or pustules that appear spontaneously in patients with Behçet's syndrome. Therefore, an investigation into the formation of the SPR lesion may contribute to the pathophysiology of skin lesions of this unique disorder. OBJECTIVE: To evaluate the immunological features of SPR formation by assessing the immunohistochemical staining of cell adhesion molecules and endothelial growth factor markers such as E-selectin, P-selectin and endoglin (CD 105). METHODS: Patients with Behçet's syndrome showing positive (n = 15) or negative (n = 10) SPR and 15 age- and sex-matched hospital-based healthy control subjects from a similar ethnic background were included in this study. Patients were divided into active and inactive stage by clinical findings and acute-phase reactant parameters including erythrocyte sedimentation rate (ESR) and neutrophil count. Punch biopsy specimens were obtained both from the lesion site on the forearms at 48 h and from normal skin approximately 5 cm adjacent to the SPR site. A biopsy was also obtained from the test application site in Behçet's syndrome patients with negative SPR and healthy volunteers. Biopsy specimens were then evaluated by immunohistochemical staining. RESULTS: Immunohistochemical examination demonstrated a mixed inflammatory cell infiltrate around the vessels and skin appendages that extended somewhat into the deep dermis. A positive segmental staining of E-selectin and P-selectin was noted in the endothelial cells of biopsies obtained from the patients with positive SPR. A positive segmental staining of CD 105 in the endothelial cells was also observed in the same group of patients. However, the immunostaining of the same markers was found to be negative in the biopsies obtained from normal skin of SPR-positive patients, SPR-negative patients and healthy control subjects. Both acute-phase reactant levels were significantly higher in the active stage than in inactive patients or healthy controls. CONCLUSION: Interaction of cellular adhesion molecules together with endothelial proliferation may play an important role in the formation of SPR lesions in patients with Behçet's syndrome. The involvement of the vascular endothelium in a large number of diseases including Behçet's syndrome supports the importance of vascular-specific adhesion molecules for their aetiopathogenesis.

The relationship between expression of p53/bcl-2 and clinicopathological criteria in cervix squamous cell carcinomas.

OBJECTIVE: Thirty cases with squamous carcinomas of cervix who underwent total abdominal hysterectomy and bilateral salphingo-oopherectomy were reviewed histopathologically. MATERIALS AND METHODS: The tissues were stained immunohistologically with p53 and bcl-2. Ten cases were selected as well differentiated (large cell keratinizing) carcinoma, ten cases moderately differentiated (large cell non keratinizing) carcinoma and ten cases poorly differentiated carcinoma (includes small cell squamous cell carcinoma). RESULTS: We observed 11 cases (36.6%) with bcl-2 and 13 cases (43.3%) with p53 positivity. P53 expression showed the opposite correlation to bcl-2 staining. CONCLUSION: A decrease in bcl-2 reactivity and an increase in p53 positive staining was noted as the histological differentiation worsened.

Association of the Gln27Glu polymorphism of the beta-2-adrenergic receptor with preterm labor.

OBJECTIVES: To investigate a potential association between the beta-2-adrenergic receptor (B2AR) polymorphisms occurring at amino acid positions 16 (Arg16Gly) and 27 (Gln27Glu) and preterm labor. METHODS: Eighty patients with preterm labor and 76 control subjects were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: A significant association was found between Gln27Glu substitution and preterm labor (P=0.001). The frequency of Gly16 and Glu27 alleles were found to be higher in patients than in control women (0.54 vs. 0.48 and 0.42 vs. 0.26, respectively), and the odds ratio for the occurrence of preterm labor was 2.14 (95% CI, 1.32-3.46; P=0.002) for the Glu 27 allele. An early delivery was noted in 52.5% of patients. CONCLUSION: The Gln27Glu polymorphism of the B2AR gene may have a role in molecular pathogenesis of preterm labor. Glu27 allele in patients with preterm labor might be a risk factor for deliveries before 37 weeks of gestation.

The effects of tamoxifen on rat skin.

BACKGROUND: Tamoxifen (Tx) is used mostly in the treatment of breast and gynecological cancers. It is also widely used in the treatment of different dermatological disorders. However, its effects on skin have not been investigated previously. OBJECTIVE: To investigate the effects of Tx administration on rat skin. METHODS: Forty Spraque-Dawley female newborn rats were separated into two control groups and two experimental groups (n 10). One day after birth, the control groups of newborn rats were given 0.02 ml saline subcutaneously (s.c.) daily whereas experimental litters were treated with 100 microg Tx citrate in 0.02 ml saline s.c. daily for five days. The first control group and experimental group of rats were anesthetized at 21 days whereas the second control group and experimental group of rats were anesthetized on the 28th day. Histopathological assessments were made and compared with the control groups. RESULTS: Abnormal hair follicles were observed in both experimental groups of rats. Epidermal atrophy together with increased dermal fibrosis was more prominent in the first experimental group. Dermal fibrosis and lymphohistiocytic inflammatory cell infiltration were found to be prominent around the hair follicles in the second experimental group. CONCLUSION: Considerable harmful effects of Tx administration were observed on rat skin.

Atypical familial Papillon-Lefèvre syndrome.

The Papillon-Lefèvre syndrome is a rare autosomal recessive disorder. Consanguinity seems a notable prerequisite. Papillon-Lefèvre syndrome manifests in the first 6 months of life with rapidly progressive periodontitis and severe alveolar bone destruction leading to early loss of both the deciduous and permanent teeth in association with palmo-plantar hyperkeratosis. We present two unusual cases of familial Papillon-Lefèvre syndrome, one of whom has only late onset of mild skin lesions and the other has severe skin lesions and relatively mild periodontal disease. A number of other cases recently described have also had atypical features.

Effects of unilateral uterine artery ligation on skin development.

BACKGROUND: It has been previously demonstrated that intrauterine growth retardation (IUGR) due to vascular insufficiency in humans results in newborn infants with marked loss of subcutaneous fat and decreased content of differentiation-specific epidermal structural proteins. OBJECTIVE: In this study, the teratogenic effects of impaired maternal blood flow were investigated histologically on rat skin. MATERIALS & METHODS: Twenty Spraque-Dawley female rats were separated into two groups (n = 10), a control (sham-operated) and an experimental group. The experimental group of fetal rats were subjected to IUGR by unilateral ligation of the maternal uterine artery on the 18th day of pregnancy. The maternal rats were subjected to cesarean hysterectomy on the 21st day of pregnancy and a skin biopsy was taken from the respective litters of both groups. RESULTS: In histopathological examination, normal epidermis and dermis were observed in the control group of litters and littermate rats from the opposite uterine horn (non-ligated side). A statistically significant reduced body weight and height were noted in the ligated side of the litters. CONCLUSION: Our findings give further evidence to the concept that normal maternal blood flow is essential for fetal growth and decreased maternal blood flow may create an impairment in skin development.

The effects of sialoadenectomy & flutamide on skin development.

BACKGROUND: Epidermal growth factor is a low molecular weight polypeptide with 53 amino acids and is known to stimulate cell proliferation and differentiation in a wide range of tissues. The submandibulary gland in the mouse is a rich source of epidermal growth factor and decreased plasma epidermal growth factor levels have been observed after sialoadenectomy (removal of the submandibular glands). Furthermore. there is evidence that epidermal growth factor stimulates spermatogenesis and reverses antiandrogen induced cryptorchidism. OBJECTIVE: In the present study, the teratogenic effects of sialoadenectomy and antiandrogen (flutamide) administration on rat skin were investigated histologically. MATERIALS & METHODS: Thirty Spraque-Dawley female rats were separated into three groups (n = 10), a control (sham-operated) and two experimental groups. The first experimental group of rats were subjected to sialoadenectomy in order to create maternal EGF deficiency one month before copulation. The second experimental group of rats were given flutamide (10 mg/100 g) for ten days during pregnancy. Three months after birth, a penile skin biopsy was taken from respective offspring in all groups. RESULTS: A statistically significant reduced body weight and length were noted in the first group of litters (maternal EGF deficient) and in the flutamide administered group when compared to the control group. Atrophic epidermis and dermal adnexa were observed histologically as the teratogenic effects of sialoadenectomy and flutamide administration on rat skin development. CONCLUSION: Epidermal growth factor is a key hormone for skin development and antiandrogen administration may insult this process by interfering with epidermal growth factor metabolism.

Effects of clomiphene citrate on neonatal rat skin.

BACKGROUND: Clomiphene citrate is chemically related to non-steroidal estrogens, and has antiestrogenic properties. It is used in the treatment of anovulatory female infertility and its therapeutic effect mainly depends on inhibiting the negative feedback effects of endogenous estrogen by stimulating the gonadotropin releasing hormone. Today, it is also used in the treatment of male infertility. OBJECTIVES: In this study the effects of clomiphene citrate on skin maturation in neonatal rats were investigated. METHODS: Forty Spraque-Dawley female newborn rats were separated into two control and two experimental groups (n = 10). One day after birth. experimental newborn rats were given clomphene citrate subcutaneously in a dosage of 100 mg/kg/day for five days. The first experimental group of rats were anesthetised at 21 days whereas the second experimental group of rats were then anestetised on day 28. Biopsies were taken immediately from the perineal skin. Histopathological assessments were made and compared with their control groups. RESULTS: In both the experimental groups of newborn rats, increased keratinization and irregular hypertrophy were observed in the epidermal cells. Disorganization of the basal layer cells and hyperplasia were found to be more prominent in the first experimental group and dermal fibrosis and lymphohistiocytic inflammatory cell infiltration were especially prominent around the sebaceous glands in the second experimental group. CONCLUSION: The administration of clomiphene citrate in newborn rats showed impaired skin maturation.

Teratogenic effects of nicotine on rat skin.

BACKGROUND: Nicotine is a well-known toxic alkaloid substance with several teratogenic effects. In animal studies it has been observed that nicotine led to intrauterine growth retardation and intrauterine growth abnormalities including anancephaly, neonatal death and low birth weight. However, the teratogenic effects of nicotine have not previously been observed on skin. OBJECTIVE: We performed a study in order to observe histologically the teratogenic effects of nicotine on rat skin. MATERIALS & METHODS: Ten female Wistar-albino rats were separated into two groups, a control and an experimental group (n = 5). After the first week of pregnancy, the experimental group of rats were given nicotine intraperitoneally in a dosage of 2 mg/kg for two weeks. RESULTS: Striking teratogenic effects were observed in the experimental group of neonatal rats. Increased mitotic activity was noticed in the basal cells and hypertrophic epithelial cells were prominent in the epidermis. Chronic inflammatory cell infiltrate, fibrosis and extravasation of the erythrocytes were found in the dermis and hair follicles. CONCLUSION: Considerable teratogenic effects of nicotine were observed histologically on newborn rat skin.

Congenital non-familial unilateral basaloid follicular hamartoma.

Basaloid follicular hamartoma is not a well-recognized clinical entity and has often been diagnosed as trichoepithelioma or basal cell carcinoma. It is a unique benign follicular tumour which comprises a variety of clinical manifestations. We present the case of a 24-year-old male with unilateral basaloid follicular hamartoma present at birth and later misdiagnosed as basal cell carcinoma. Histological features of basaloid follicular hamartoma are not always diagnostic and clinico-pathological correlation is particularly important to distinguish this benign hamartoma from other basaloid tumours including basal cell carcinoma. Continuous follow-up of our patient did not reveal any clinical or histological malignant transformation.

Histopathological assessment of the prophylactic effect of gingko-biloba extract on intestinal ischemia-reperfusion injury.

In this experimental study, the prophylactic effects of Gingko-Biloba Extract (GBE) were examined after experimental ischemia on intestinal wall damage. 50 Wistar-Albino rats (2.5 month old) were gathered and separated into 5 groups (n:10). Group 1 was subjected to a laparotomy (sham-operated group) whereas all other experimental groups were subjected to an occlusion of their superior mesenteric arteries for 30 minutes and a period of 20 minutes reperfusion following occlusion. Group 2 was not given any prophylactic agent during the experiment (untreated control group). GBE was administered in a dosage of 50 mg/kg (i.v.) as a prophylactic agent to Group 3 one hour prior to laparotomy whereas Group 4 was given GBE at 50 mg/kg (i.v.) just before ischemia. Group 5 was given GBE in the same dosage just before reperfusion. Immediately after reperfusion, a biopsy was taken from the ileum (10 cm proximity to ileocaecal valve) for histopathological assessment. A significant prophylactic effect of GBE was observed in Group 5 in which GBE was administered just before reperfusion.

Do microwave ovens affect the eyes?

The cataractogenic effects of the microwave oven on rat eyes were investigated histologically. Twenty-one adult Wistar-Albino rats (2-2.5 months old) were divided into three groups (n = 7): a control group (sham-exposed) and two experimental groups. The experimental rats was confined in special cages and placed next to the closed door of a microwave oven. The first experimental group was given 15 minutes of daily exposure and the second, 30 minutes, for 1 month. Biomicroscopic examination detected no pathological damage to the lens in the experimental rats. Histologically, there was a lens of single-layered epithelium in the control group. In the first experimental group, there was slight pleomorphism in the superficial epithelial cell contours and vacuolizations in the lens fibers; the second experimental group, had pronounced pleomorphism and pyknosis of the nuclei in the superficial epithelium. Some of the superficial epithelial cells had disappeared and were histologically observed as acellular areas. Single-layered epithelium became disorganized and formed multilayered epithelial groups in the superficial epithelium. Vacuolization was more prominent in this group. Personal exposure from microwave ovens is generally minimal because of the rapid decrease in power density with distance. Microwave oven users do not normally stand as close to the oven as the rats in our study were placed; therefore, it is difficult to suggest that microwave ovens always have cataractogenic effects on human eyes.

Omeprazole, nitrendipine, famotidine and stress-induced ulcers.

BACKGROUND: Omeprazole inhibits gastric acid secretion by blocking the proton pump of the gastric parietal cell. Nitrendipine is a derivative of the dihydropyridine group of calcium channel blockers and administrated for angina and hypertension. Famotidine is one of the newer histamine H2-receptor antagonists and heals gastric and duodenal ulcers by reducing gastric acid output. OBJECTIVES: The healing effects of omeprazole, nitrendipine and famotidine on stress-induced gastric ulcers were investigated in rats. METHODS: Forty male Wistar-albino rats were separated into five groups (n = 8), a control (non-stress) and four experimental (stress) groups. Experimental rats were treated with omeprazole, nitrendipine, famotidine or a placebo after the stresses of starvation and cold-restraint. RESULT: Macroscopically, the mean area of the affected lesional mucosa was 1/4 of the total gastric mucosa in the famotidine treated group and 1/5 of the total gastric mucosa in the nitrendipine treated group. A considerably decrease was observed in the omeprazole treated group in which the mean area of the lesional mucosa was only in 1/8 of the total gastric mucosa. On microscopic examination, congestive vessels and chronic inflammatory cell infiltrates were significantly reduced in the omeprazole treated group. Tissue regeneration was more prominent in the omeprazole group than the other groups. CONCLUSION: Omeprazole was found to be superior in terms of the effect on the healing process to nitrendipine and famotidine. Although therapeutic effects of nitrendipine and famotidine were observed, those were less than omeprazole.

Comparison of microsuturing to the use of tissue adhesives in anastomosing sciatic nerve cuts in rats.

The purpose of this study was to investigate and to compare the effects of microsuturing to that of tissue adhesives (Tisseel) on the healing of anastomosing peripheral nerve incisions. Forty-five Wistar-Albino rats were placed in special cages and separated into three groups (n = 15). In the control group, biliteral sciatic nerves were explored but no incision was made. In the first experimental group, bilateral sciatic nerves were incised and end-to-end anastomosing was performed by microsuturing the epineurium. In the second experimental group, tissue adhesive (Tisseel) was used alone in anastomosing the sciatic nerve cuts. Assessments of the healing processes were demonstrated by 1.electromyography (EMG), 2. measuring the electrical responses of the anastomosed nerves after electrical stimuli, 3. histopathological examination. Statistical analysis of the EMG findings showed that the Tisseel group was the closest in the healing process to the control group. After applying electrical stimuli to the dissected nerves, the resistance value of the Tisseel group was nearest to those of the control group. The histopathological examinations showed highly degenerative nerve bundles and prominent foreign body granuloma at the anastomosed sites of the microsutured group. The granulomatous inflammation was observed to be much less in the Tisseel group. We conclude that the healing effect of Tisseel was found to be superior to that of microsuturing as demonstrated by the findings of EMG, electrical responses of the anastomosed nerves, and histopathological examination.

Acceptable radiation leakage of microwave ovens on pregnant and newborn rat brains.

The present article was intended to investigate the possible effects of the acceptable radiation leakage of microwave ovens on pregnant and new-born rat brains. Twenty-seven pregnant Wistar-albino rats were separated into three groups (n = 9), a control group (sham-exposed) and two experimental groups. The experimental gravid rats were confined in Plexiglas cages and placed next to the closed door of a microwave oven (power-output: 550 W). The NIR 15 (NIR: non-ionising radiation) group of gravid rats were exposed to the leakage of microwave ovens daily for 15 minutes whereas the NIR 30 group was exposed daily for 30 minutes during their pregnancies. The most striking changes were observed in the NIR 30 group of rats. Congestive vessels, edema and degenerative neurones were noticed in all experimental dams. Chronic inflammatory cell infiltrate, and focal necrosis of neurones were seen only in the NIR 30 group of dams. Progressive edema and conspicuous congestive vessels were seen in the offspring of both experimental groups. Chronic inflammatory cell infiltrate, haemorrhage, necrotic neural tissues, and degenerative neurones with a reactive glial proliferation were observed only in the offspring of the NIR 30 groups.