Murat Alper

Investigations on the in vivo wound healing potential of Hypericum perforatum L.

ETHNOPHARMACOLOGICAL RELEVANCE Olive oil extract of the flowering aerial parts of Hypericum perforatum L. (Hypericaceae) is a popular folk remedy for the treatment of wounds in Turkey. AIM OF THE STUDY In order to prove the claimed utilization of the plant, the effects of the extracts and the fractions were investigated by using bioassay-guided procedures. For the wound healing activity assessment, in vivo excision and incision wound models were applied. For the anti-inflammatory activity, an in vivo model, based on the inhibition of acetic acid-induced increase in capillary permeability was used as well. Moreover, a parallel study was run on Hypericum scabrum L., which is a widespread species of the gender but not known as a folk remedy for wound healing, to provide a preliminary data to compare and emphasize the selection of correct plant species. RESULTS Initial investigations proved that the olive oil extract of Hypericum perforatum has a significant wound healing effect on excision (5.1-82.6% inhibition) and circular incision (20.2-100.0% inhibition) wound models. In order to determine the active wound healing ingredient(s), aerial parts of the plant was extracted with ethanol, noteworthy wound healing activity profile was observed with the wound models; between 18.3% and 95.6% in excision model and from 13.9% to 100.0% inhibitions in incision model were determined. The ethanolic extract was then submitted to successive solvent extractions with n-hexane, chloroform and ethyl acetate (EtOAc). Each solvent extract was also applied on the same wound models, consequently, EtOAc subextract was found to be the most active one by inhibiting wounds between 17.9% and 100.0% in excision model, subsequently between 9.4% and 100.0% in incision model. However, all subfractions obtained from the EtOAc subextract using Sephadex LH-20 column chromatography showed wound healing activity not more than the whole EtOAc subextract, which revealed that a possible synergistic activity that might be questioned. Among the active Sephadex fractions, Fr. A further yielded hyperoside, isoquercitrin, rutin and (-)-epicatechin and Fr. B yielded hypericin as the major components. Moreover, a dose-dependent anti-inflammatory activity was found for the ethanol extract, EtOAc subextract and Sephadex fractions of Hypericum perforatum. These results suggest that anti-inflammatory activity of the active fractions might have a contributory role in the wound healing effect of the plant. CONCLUSION Results of the present study have proved that aerial parts of Hypericum perforatum possess remarkable wound healing and anti-inflammatory activities supporting the folkloric assertion of the plant in Turkish folk medicine. Flavonoids [hyperoside, isoquercitrin, rutin and (-)-epicatechin] and naphthoquinones (hypericins) were found as the active components of Hypericum perforatum. On the other hand, ethanol extract of Hypericum scabrum showed neither remarkable wound healing nor anti-inflammatory activity demonstrating the importance of correct plant species selection in therapeutic applications.

A new mutation of the fukutin gene in a non‐Japanese patient

Fukuyama‐type congenital muscular dystrophy (FCMD), Walker–Warburg syndrome, and muscle‐eye‐brain disease are clinically similar autosomal recessive disorders characterized by congenital muscular dystrophy, cobblestone lissencephaly, and eye anomalies. FCMD is frequent in Japan, but no FCMD patient with confirmed fukutin gene mutations has been identified in a non‐Japanese population. Here, we describe a Turkish CMD patient with severe brain and eye anomalies. Sequence analysis of the patients DNA identified a homozygous 1bp insertion mutation in exon 5 of the fukutin gene. To our knowledge, this is the first case worldwide in which a fukutin mutation has been found outside the Japanese population. This report emphasizes the importance of considering fukutin mutations for diagnostic purposes outside of Japan. Ann Neurol 2003

Primary subcutaneous cyst hydatic disease in proximal thigh: an unusual localisation: a case report

BackgroundMusculoskeletal hydatidosis is very rare and represents 1% – 5.4% of all cases of echinococcosis. On clinical basis, infection mimics a soft-tissue tumor, and the preoperative radiological diagnosis is very important to avoid biopsy.Case PresentationWe report an unusual case of primary subcutaneous hydatidosis in proximity to vastus lateralis muscle. It was diagnosed according to the computed tomography appearance, clinical and pathological findings. A 43 year old female patient was admitted with a history of pain at proximal thigh for the last 30 days. On physical examination, a mass which was 4 × 5 cm in diameter, painful and erythamatous, was palpated over greater trochanter. Sedimentation rate was 40 mm in the first hour. CT (Computed Tomography) scan demonstrated, a soft tissue mass with central cystic component in the subcutaneous tissue near vastus lateralis muscle.Histopathological examination of the specimen revealed a pericystic structure, which consisted of connective tissue and scattered hyaline cells showing a necrotic basophilic structure that resembled a cuticular membrane. Treatment with high dose albendazole was conducted for 4 weeks.ConclusionsThis case illustrates that echinococcal disease should be considered in the differential diagnosis of every cystic mass in every anatomic location, especially when they occur in areas where the disease is endemic.

Hepatic Energy Metabolism and the Differential Protective Effects of Sevoflurane and Isoflurane Anesthesia in a Rat Hepatic Ischemia-Reperfusion Injury Model

BACKGROUND: We investigated the effects of isoflurane and sevoflurane in a warm liver ischemia-reperfusion (IR) model on cytokines, hepatic tissue blood flow (HTBF), energy content, and liver structure. METHODS: Seventy-two Wistar rats were randomly assigned into 1 of 3 groups: Control group, no volatile anesthetics; sevoflurane group, 2% sevoflurane; isoflurane group, 1.5% isoflurane. Thirty minutes after the start of volatile anesthetics, rats were subjected to 45 min hepatic ischemia and 2 and 4 h of reperfusion. Rats were killed at the end of ischemia, 2 and 4 h of reperfusion. Aspartate aminotransferase and alanine aminotransferase, HTBF, malondialdehyde, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, energy charge, and histologic examination were used to evaluate the extent of liver injury. RESULTS: Serum alanine aminotransferase and aspartate aminotransferase levels were similar in control and isoflurane groups while there was a significant decrease in the sevoflurane group in the postischemic period (P < 0.01). HTBF was remarkably better in the sevoflurane group than in the isoflurane group and worse in the control group. Tissue malondialdehyde levels were significantly low in the sevoflurane group compared with the isoflurane group at 2 h of reperfusion (P < 0.05) and reached its maximum value in the postischemic period in the control group. After ischemia, 2 and 4 h of reperfusion, tumor necrosis factor-α and interleukin-1β values were lowest in the sevoflurane group and highest in the control group but it was not statistically significant (P > 0.05). In the sevoflurane group, hepatic adenosine triphosphate and energy charge were significantly high at all measurement times. At the postischemic period, energy charge was lower compared with the sevoflurane and isoflurane groups. The degree of hepatocyte injury was small in the sevoflurane group. CONCLUSIONS: Clinically relevant concentrations of sevoflurane given before, during, and after hepatic ischemia protected the liver against IR injury, whereas the effects of isoflurane on hepatic IR injury were not notable.

EGFR expression and gene copy number in triple-negative breast carcinoma

Most basal-like breast carcinomas are estrogen receptor negative, progesterone receptor negative, and cerb-B2/HER-2/neu negative--the so-called triple-negative breast carcinomas--with high epidermal growth factor receptor (EGFR) expression, which makes EGFR a target of treatment. We evaluated EGFR expression by immunohistochemistry (IHC) with two different clones (EGFR.31G7 and EGFR.25) and gene copy number by fluorescence in situ hybridization (FISH) with Locus specific identifier EGFR/CEP 7 dual probe in 62 triple-negative breast carcinomas. Any complete or incomplete membranous and/or cytoplasmic expression was regarded as IHC positive. Cases showing gene amplification (a ratio of EGFR gene to chromosome 7 of ≥ 2 or 15 copies per cell in ≥ 10% of cells) and high polysomy (≥ 4 copies in ≥ 40% of cells) were considered FISH po sitive. We detected EGFR.31G7 positivity in 38 of 62 cases (61.4%), which was composed of 12 of 62 (19.4%) cytoplasmic, 14 of 62 (22.6%) incomplete membranous, and 12 of 62 (19.4%) complete membranous staining. Among 38 of 49 (77.6%) EGFR.25-positive cases, 7 of 49 (14.3%) exhibited cytoplasmic, 10 of 49 (20.4%) exhibited incomplete membranous, and 21 of 49 (42.9%) exhibited complete membranous staining pattern. Ten of 62 (16.1%) FISH-positive cases were identified; 1 of 62 (1.6%) showed amplification, and the rest showed high polysomy. All FISH-positive cases were also found to be IHC positive (P = 0.01) by both EGFR clones. The amplified case displayed strong complete membranous staining with both clones. Among the high polysomic cases; 4 of 9 (44.4%) incomplete membranous, 4 of 9 (44.4%) complete membranous and 1 of 9 (11.1%) cytoplasmic expression of EGFR.31G7, and 6 of 8 (75%) complete membranous and 2 of 6 (25%) cytoplasmic expression of EGFR.25 were detected. Here, we report that membranous EGFR expression is associated with increased gene copy number (P = 0.035 for EGFR.31G7 and P = 0.026 for EGFR.25 clone). Because the markers to predict anti-EGFR treatment response in other system tumors such as EGFR mutation and amplification seem to be rare events in breast cancer, membranous staining pattern of EGFR might be the best way to decide the patient eligibility for anti-EGFR therapy.

Volatile anesthetic preconditioning attenuated sepsis induced lung inflammation

BACKGROUND This study aimed to evaluate the differential protective effects of isoflurane or sevoflurane on lung inflammation in a rat model of cecal ligation and puncture (CLP) induced sepsis. METHODS Seventy-two rats were assigned to control, sevoflurane, or isoflurane groups. At 2 and 4 h, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β), nitrate/nitrate levels (NO), total antioxidant capacity (TAC), and intercellular cell adhesion molecule-1 (ICAM-1) were determined. At 12 and 24 h, malondialdehyde (MDA), myeloperoxidase (MPO), and histologic changes were evaluated. Survival was monitored for 7 d after CLP. RESULTS Sevoflurane (75%) and isoflurane (63%) significantly improved survival rate compared with control rats (38%). When sevoflurane and isoflurane groups were compared, sevoflurane pretreatment showed significant decrease in NO at 2 h [1045 (803-1274)/1570 (1174-2239) and 4 h [817 (499-1171)/1493 (794-2080)]; increase in TAC at 4 h [580.0 (387-751)/320 (239-512)]; decrease in MDA at 12 h [2.5 (1.1-4.2)/5.4 (4-73)] and 24 h [10.8 (6.0-14.0)/15.9 (9-28)]; and decrease in MPO at 24 h [145.8 (81-260)/232 (148-346)]. The difference in the ICAM-1 expression of the isoflurane and sevoflurane groups was not significant at both measurement times. The architectural integrity of the alveoli was preserved in all the groups. The injury scores of the three groups at 12 and 24 h did not show any significant difference. CONCLUSIONS Both sevoflurane and isoflurane attenuated inflammatory response, lipid peroxidation, and oxidative stress. Furthermore, sevoflurane was more effective in modulating sepsis induced inflammatory response at the chosen concentration in sepsis model.

Extensive cutaneous metastasis of transitional cell carcinoma of the bladder

Abstract Cutaneous metastasis of bladder carcinoma is extremely rare. Iatrogenic implantations have been the main cause in the majority of cases of transitional cell carcinoma with cutaneous metastasis. Otherwise, primary cutaneous metastasis is accepted as the late manifestation of systemic spread. The present paper describes a case of relatively early and extensive skin metastasis of transitional cell carcinoma in a 78‐year‐old man. The patient had a histopathological diagnosis of poorly differentiated (grade III) muscle invasive transitional cell carcinoma with a staging of T2NOMO 6 months prior to presenting. He presented to our outpatient clinic with a 3‐month history of skin lesions as multiple, rubbery subcutaneous nodules. Radiological reinvestigation revealed no other metastatic site (including bone and lung), except for a metastatic nodule in the liver. The present paper reports an interesting and rare case of extensive skin metastasis of transitional cell carcinoma as the primary complaint.

A rare malignancy of the parotid gland: oncocytic carcinoma

Oncocytic carcinomas are uncommon; they represent 11% of all oncocytic salivary gland neoplasms, 0.5% of all epithelial salivary gland malignancies and 0.18% of all epithelial salivary gland tumors. A 65-year-old woman was admitted to our ENT clinic with a history of a painless left preauricular mass. No lymph node was palpable on either side of her neck. Computed tomography demonstrated a 3×3-cm solid lesion in the left parotid gland. As oncocytes and atypical cells were seen at the cytologic examination of a fine-needle aspiration biopsy, this finding suggested a malignant epithelial tumor. Total parotidectomy by preserving the facial nerve was performed. The result of the pathologic examination was oncocytic carcinoma regarding histopathologic and immunohistochemical findings and especially the invasive growth pattern. We preferred a close follow-up to an elective neck dissection, and reserved the neck dissection for a recurrence. The prognosis of oncocytic carcinomas is not well known because of their low incidence. Further investigation of the prognosis of patients with oncocytic carcinoma of the parotid gland is warranted as more cases are reported.

The preparation of ciprofloxacin hydrochloride-loaded chitosan and pectin microspheres: THEIR EVALUATION IN AN ANIMAL OSTEOMYELITIS MODEL

Ciprofloxacin hydrochloride-loaded microspheres were prepared by a spray-drying method using pectin and chitosan. The effects of different polymers and drug ratios were investigated. The most appropriate carriers were selected by in vitro testing. A rat methicillin-resistant Staphylococcus aureus osteomyelitis model was used to evaluate the effects of the loaded microspheres. The drug was released rapidly from the pectin carrier but this was more sustained in the chitosan formulation.Chitosan microspheres loaded with ciprofloxacin hydrochloride were more effective for the treatment of osteomyelitis than equivalent intramuscular antibiotics.

Persistent serpentine supravenous hyperpigmented eruption associated with docetaxel

Various mucocutaneous reactions have been reported with the use of systemic docetaxel. We describe a 47‐year‐old man who developed a persistent serpentine supravenous hyperpigmented eruption (PSSHE), beginning at the site of docetaxel injection and spreading along the superficial venous network in the anterior aspect of the right forearm and distal arm. The eruption occurred after the first infusion of docetaxel following insufficient venous washing. A second infusion was administered through a vein in the other forearm, but this time, abundant venous washing was performed and a similar eruption did not occur. To our knowledge, this is the second report of docetaxel‐induced supravenous discoloration and we discussed the terminology and mechanism of this unique reaction.