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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.

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The case of a 14-year-old girl suffering from Klippel-Trenaunay syndrome associated with multiple port-wine stain type vascular anomalies and varicose veins involving upper limbs is described. Finger deformations are common in Klippel-Trenaunay syndrome. In our patient, striking hypertrophy of soft tissues and overgrowth of bones were observed on both forearms and finger deformations were observed particularly on right thumb and index finger. Although lower limb involvement is very common amongst the patients with Klippel-Trenaunay syndrome, in our patient involvement of the lower limbs was not observed.

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BACKGROUND: Anastrozole is a third-generation nonsteroidal aromatase inhibitor which is used in the treatment of breast cancers. Anastrozole has also been used in the treatment of dermatomyositis skin eruptions but its direct effects on skin have not been well documented. OBJECTIVE: To study the effects of anastrozole administration on neonatal rat skin. METHODS: Forty Sprague-Dawley female newborn rats were separated into two control groups and two experimental groups (n = 10). One day after birth the control group of newborn rats were given daily 0.02 ml saline subcutaneously for a period of 15 days. The first experimental group of rats were treated with 0.05 mg/100g/day anastrozole subcutaneously for 15 days whereas the second experimental group of rats were given 0.25 mg/100g/day anastrozole subcutaneously for 15 days. Histopathological assessments were made and compared with the control groups. RESULTS: Increased keratinization, strippling, hypertrophic epidermal cells and disorganization of the epidermal cells were observed in the first experimental group. In the second experimental group in addition to these pathologic findings acantholysis was observed. CONCLUSION: The administration of anastrazole in newborn rats showed considerable harmful effects.

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OBJECTIVE: To assess neurotological status and its ophthalmological correlates in Behçet's disease. STUDY DESIGN: A cross sectional study in which 17 patients with Behçet's disease and 13 healthy controls were included. PATIENTS AND METHODS: The patients were divided into two groups: those with and without end stage ocular involvement. Neurotological status was evaluated with audiological tests (pure tone and speech audiometry, tympanometry, short increment sensitivity index, tone decay, and evoked response audiometry), and Dix-Halpike positional testing. RESULTS: The positional test was normal. The audiological test results of the patients with and without end stage ocular involvement were not significantly different (p>0.05). A sloping audiogram with bilateral symmetric and mild sensorineural hearing loss was the main audiogram obtained. There was no relationship between the presence or absence of the end stage ocular involvement and the otological parameters studied excluding I-III interval on evoked response audiometry (p>0.05). CONCLUSION: Although the main underlying pathogenetic factor in Behçet's disease is the autoimmune vasculitis, the mechanisms involved in the pathogenesis of neurological and ocular damage may be different. Alternatively, the differential involvement of certain organ systems may not reflect the nature of the disease process itself, but rather the manner in which each organ responds to injury.

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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.

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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.

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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.

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BACKGROUND: Vasospasm is one of the underlying causes of morbidity and mortality in subarachnoid haemorrhage (SAH). The therapeutic effects of intracarotid infusion of spermine/nitric oxide complex (SPER/NO) on cerebral vasospasm in an experimental model of SAH were investigated. METHOD: Twenty-four adult male New Zealand white rabbits (2.6-3.4 kg in weight) were randomly divided into four groups (n=6), as follows: (I) control group (without SAH and drug), (II) SAH alone group (with SAH, without drug), (III) SAH placebo group (with SAH and saline), and (IV) SAH-SPER/NO group (with SAH and SPER/NO). The fresh autologous non-heparinized blood was injected into the cisterna magna to induce a SAH, after 24 hour SAH, the substance (saline or SPER/NO) was delivered to animals. All rabbits were scarified at 48-hours of induced SAH. The basilar artery with surrounding tissue was removed from the cranium and processed for paraffin embedding. Histopathological and stereological examinations of the basilar artery were done. FINDINGS: In the SPER/NO treated group of rabbits, the histopathological changes were less severe than in the SAH-alone and SAH-placebo groups. Regarding the intracarotid pressure, there was a statistically significant difference between SAH-alone and SAH-SPER/NO groups and also between SAH-SPER/NO and control groups (p<0.05). The mean cross sectional area of basilar arteries was 0.26 mm(2) in the control, whereas in SAH alone, placebo and SAH-SPER/NO groups were 0.13, 0.15 and 0.20 mm(2), respectively. INTERPRETATION: It is well known that NO is a critical substance involved in cerebral vascular dynamics. Present results indicate that treatment of vasospasm with SPER/NO in SAH may be promising. However, further studies should be done on this substance to clarify its effect on vasospasm before using the drug in clinical situations.

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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.

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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.

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To determine the standard width and shape of the nasolacrimal canal (NLC) in the coronal plane, a retrospective review of 950 coronal paranasal CT sections was undertaken. The coronal diameter of NLC was measured at its upper and lower ends and anomalies in its configuration noted. The mean diameters of the NLC were 4.8 +/- 1.2 mm and 4.7 +/- 1.1 mm on the right and left sides, respectively. There was no difference in the mean NLC diameter between the right and left sides, upper and lower portions or males and females. In two cases, an abnormal dilation of the NLC at its inferior portion was encountered. A marked enlargement of the NLC can occur in the absence of a neoplastic or obstructive process and may be detected as an isolated finding representing idiopathic or congenital enlargement. Segmental NLC dilatation is not always an indicator of pathology, particularly in asymptomatic cases, and should be considered a rare anatomic variation.

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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.

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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.

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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.

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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.

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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.

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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.

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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.

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