Enhanced topical delivery of dexamethasone by ß-cyclodextrin decorated thermoresponsive nanogels.

Highly hydrophilic, responsive nanogels are attractive as potential systems for the topical delivery of bioactives encapsulated in their three-dimensional polymeric scaffold. Yet, these drug carrier systems suffer from drawbacks for efficient delivery of hydrophobic drugs. Addressing this, ß-cyclodextrin (ßCD) could be successfully introduced into the drug carrier systems by exploiting its unique affinity toward dexamethasone (DXM) as well as its role as topical penetration enhancer. The properties of ßCD could be combined with those of thermoresponsive nanogels (tNGs) based on dendritic polyglycerol (dPG) as a crosslinker and linear thermoresponsive polyglycerol (tPG) inducing responsiveness to temperature changes. Electron paramagnetic resonance (EPR) studies localized the drug within the hydrophobic cavity of ßCD by differences in its mobility and environmental polarity. In fact, the fabricated carriers combining a particulate delivery system with a conventional penetration enhancer, resulted in an efficient delivery of DXM to the epidermis and the dermis of human skin ex vivo (enhancement compared to commercial DXM cream: ∼2.5 fold in epidermis, ∼30 fold in dermis). Furthermore, DXM encapsulated in ßCD tNGs applied to skin equivalents downregulated the expression of proinflammatory thymic stromal lymphopoietin (TSLP) and outperformed a commercially available DXM cream.

The efficacy and safety of capecitabine plus bevacizumab combination as first-line treatment in elderly metastatic colorectal cancer patients

Aim: The optimal treatment in older persons with metastatic colorectal cancer (mCRC) is complicated by a lack of general agreement. The aim of this study was to evaluate the activity of bevacizumab plus capecitabine combination in elderly mCRC patients who were not suitable for chemotherapy with irinotecan and oxaliplatin-containing regimens. Materials and methods: Seventy years and older patients with metastatic colorectal carcinoma were included in this retrospective study. Bevacizumab was administered at a dose of 7.5 mg/kg on day 1 as an intravenous (IV) infusion over 30-90 min every 21 days, and capecitabine was prescribed at 1000 mg/m2 twice daily on days 1-14 of the same 21-day schedule. Results: Eighty-two consecutive patients (47 men, 35 women) were included in the study. The mean age was 75.5 (SD 3.9, range 70-87). Half of the patients were older than 75 years. There were 55 patients (67.1 %) with a good Eastern Cooperative Oncology Group (ECOG) performance status (PS: 0-1) and the remaining 27 patients (32.9 %) had a poor ECOG performance status (PS: 2). With a median follow-up period of 18.5 months, the median progression-free survival (PFS) was 10 months (95 % CI, 7.8-12.1) and the median OS was 25 months (95 % CI, 18.6-31.3). The main toxicities recorded were non-hematological. Thirty-one patients (37 %) experienced grade 3/4 adverse events, the most common being hand–foot syndrome (9.8 %). No fatal toxicity resulting from this regimen was recorded. Conclusions: Considering the toxicity profile and survival outcomes, the combination regimen of capecitabine and bevacizumab is a potentially feasible treatment option in elderly mCRC patients (AU)

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Increased asymmetric dimethylarginine levels in severe transient tachypnea of the newborn.

OBJECTIVE: Nitric oxide (NO) is synthesized by NO synthase (NOS), and asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of NOS. We aimed to investigate l-arginine and ADMA levels in transient tachypnea of the newborn (TTN) and their relationship with systolic pulmonary artery pressure (PAP) and disease severity. STUDY DESIGN: Infants born at ⩾35 weeks gestational age with clinical signs and chest X-ray findings consistent with TTN were enrolled; controls were recruited at the same time. l-arginine and ADMA levels were measured at 12 to 24 h (first samples) and at 48 to 72 h (second samples). Systolic PAP was evaluated on the second day. Patients were divided according to the duration of tachypnea and designated as group A (duration ⩽72 h) and group B (duration >72 h). RESULTS: In the first samples, the ADMA levels were significantly higher in patients with TTN compared with controls (P<0.001). In the second samples, the ADMA levels were significantly higher in group B compared with that in group A (P=0.019). In group A patients, the second ADMA levels were significantly lower compared with that in the first samples (P<0.001), whereas the second ADMA levels remained unchanged compared with the first samples in group B. Systolic PAP values were significantly higher in group B compared with that in group A patients (P=0.033). CONCLUSION: Increased ADMA concentration may reduce NO synthesis, leading to increased PAP and thus longer duration of tachypnea.

The efficacy and safety of capecitabine plus bevacizumab combination as first-line treatment in elderly metastatic colorectal cancer patients.

AIM: The optimal treatment in older persons with metastatic colorectal cancer (mCRC) is complicated by a lack of general agreement. The aim of this study was to evaluate the activity of bevacizumab plus capecitabine combination in elderly mCRC patients who were not suitable for chemotherapy with irinotecan and oxaliplatin-containing regimens. MATERIALS AND METHODS: Seventy years and older patients with metastatic colorectal carcinoma were included in this retrospective study. Bevacizumab was administered at a dose of 7.5 mg/kg on day 1 as an intravenous (IV) infusion over 30-90 min every 21 days, and capecitabine was prescribed at 1000 mg/m(2) twice daily on days 1-14 of the same 21-day schedule. RESULTS: Eighty-two consecutive patients (47 men, 35 women) were included in the study. The mean age was 75.5 (SD 3.9, range 70-87). Half of the patients were older than 75 years. There were 55 patients (67.1 %) with a good Eastern Cooperative Oncology Group (ECOG) performance status (PS: 0-1) and the remaining 27 patients (32.9 %) had a poor ECOG performance status (PS: 2). With a median follow-up period of 18.5 months, the median progression-free survival (PFS) was 10 months (95 % CI, 7.8-12.1) and the median OS was 25 months (95 % CI, 18.6-31.3). The main toxicities recorded were non-hematological. Thirty-one patients (37 %) experienced grade 3/4 adverse events, the most common being hand-foot syndrome (9.8 %). No fatal toxicity resulting from this regimen was recorded. CONCLUSIONS: Considering the toxicity profile and survival outcomes, the combination regimen of capecitabine and bevacizumab is a potentially feasible treatment option in elderly mCRC patients.

AN UNUSUAL PRESENTATION OF JOUBERT SYNDROME AND RELATED DISORDERS IN A NEWBORN: PANHYPOPITUITARISM.

The Joubert syndrome is characterized by hypotonia, ataxia, facial dysmorphism, abnormal eye movement, irregular breathing pattern and cognitive impairment. The molar tooth sign is the pathognomonic midbrain-hindbrain malformation for Joubert syndrome. Joubert syndrome and related disorders (JSRD), are the clinically and genetically heterogen disorders in which the obligatory hallmark is the molar tooth sign (MTS). In this report, it was described the association of the molar tooth sign, absence of pituitary gland and corpus callosum agenesis on an infant with JSRD. To the best of our knowledge, this is the first case diagnosed as JSRD and panhypopituitarism without features of OFD VI.

Prognostic significance of ADAM17 expression in patients with gastric cancer who underwent curative gastrectomy

Backgrounds. A disintegrin and metalloproteinase (ADAM) 17 has been indicated to be an indispensable regulator of cellular events from proliferation to migration. Although prognostic importance of ADAM17 expression has been investigated in several tumours, its clinical utility as a useful prognostic molecular marker remains unclear in gastric cancer. In the current study, we evaluated the expression of ADAM17 and its prognostic significance in gastric cancer patients after curative gastrectomy. Methods. The prognostic significance of ADAM17 expression was analysed immunohistochemically in 156 patients with gastric cancer who had undergone curative gastrectomy, and the relationship between its expression and clinicopathological factors was also evaluated. Results. High ADAM17 expression was detected in 79 patients (51 %), whereas low expression was found in 77 cases (49 %). There was significant correlation between gender, histology, lymph node metastasis, vascular invasion, the presence of recurrence and high ADAM17 expression. Recurrence in patients with high ADAM17 expression was significantly higher than that for patients with low ADAM17 expression (p = 0.032). The median disease-free survival (DFS) time for patients with tumours with high ADAM17 expression was worse than that of patients with tumours with low ADAM17 expression (16.6 vs. 44.2 months, p = 0.004). In addition, patients with low ADAM17 expression had a higher median overall survival (OS) (49.6 vs. 26.9 months, p = 0.019) compared to those with high ADAM17 expression. Multivariate analysis indicated that the rate of ADAM17 expression was an independent prognostic factor for DFS, in addition to the already known important clinicopathological prognostic indicator. But the prognostic importance of ADAM17 expression could not be proved by multivariate analysis for OS. Conclusions. The potential value of ADAM17 expression as a useful molecular marker in gastric cancer progression should be evaluated comprehensively; it may predict recurrence and poor prognosis in patients with gastric cancer after curative resection (AU)

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Comparison of the effect of the rotation palatoplasty and V-Y pushback palatoplasty techniques on palate elongation with magnetic resonance imaging.

Most surgical techniques used in cleft palate repair require the extension of the palate to the pharynx. However, no adequate information exists regarding the extent to which this elongation obtained during operation continues in late postoperative period. In this study, we compared and measured palate elongation in patients with a cleft palate who underwent a V-Y pushback or rotation palatoplasty, by means of magnetic resonance images obtained before and 1 year after surgery. The hard palate, soft palate, and total palate lengths were measured for all of the patients, and the velopharyngeal opening area width was calculated. In patients who underwent the V-Y pushback technique (n=13), the total palate and soft palate lengths were shortened by an average of 0.10 and 0.14cm after surgery, respectively. However, the hard palate length was elongated by an average of 0.13cm. In the rotation palatoplasty group (n=13), the total palate, hard palate, and soft palate lengths were elongated by 0.57, 0.10, and 0.49cm, respectively. The velopharyngeal opening was narrowed by 0.06cm(2) using the V-Y pushback technique and by 0.29cm(2) using the rotational palatoplasty. This study demonstrated that the palate does not elongate during the V-Y pushback technique, as expected. However, rotational palatoplasty elongates the soft palate.

Prognostic significance of ADAM17 expression in patients with gastric cancer who underwent curative gastrectomy.

BACKGROUNDS: A disintegrin and metalloproteinase (ADAM) 17 has been indicated to be an indispensable regulator of cellular events from proliferation to migration. Although prognostic importance of ADAM17 expression has been investigated in several tumours, its clinical utility as a useful prognostic molecular marker remains unclear in gastric cancer. In the current study, we evaluated the expression of ADAM17 and its prognostic significance in gastric cancer patients after curative gastrectomy. METHODS: The prognostic significance of ADAM17 expression was analysed immunohistochemically in 156 patients with gastric cancer who had undergone curative gastrectomy, and the relationship between its expression and clinicopathological factors was also evaluated. RESULTS: High ADAM17 expression was detected in 79 patients (51 %), whereas low expression was found in 77 cases (49 %). There was significant correlation between gender, histology, lymph node metastasis, vascular invasion, the presence of recurrence and high ADAM17 expression. Recurrence in patients with high ADAM17 expression was significantly higher than that for patients with low ADAM17 expression (p = 0.032). The median disease-free survival (DFS) time for patients with tumours with high ADAM17 expression was worse than that of patients with tumours with low ADAM17 expression (16.6 vs. 44.2 months, p = 0.004). In addition, patients with low ADAM17 expression had a higher median overall survival (OS) (49.6 vs. 26.9 months, p = 0.019) compared to those with high ADAM17 expression. Multivariate analysis indicated that the rate of ADAM17 expression was an independent prognostic factor for DFS, in addition to the already known important clinicopathological prognostic indicator. But the prognostic importance of ADAM17 expression could not be proved by multivariate analysis for OS. CONCLUSIONS: The potential value of ADAM17 expression as a useful molecular marker in gastric cancer progression should be evaluated comprehensively; it may predict recurrence and poor prognosis in patients with gastric cancer after curative resection.

Lower cocaine- and amphetamine-regulated transcript levels pose a risk for developing PCOS.

UNLABELLED: Cocaine- and amphetamine-regulated transcript (CART) is an anorectic neuropeptide abundantly expressed in the central, peripheral, and enteric nervous systems, as well as in several different endocrine cell types. Besides regulating food intake and endocrine function, it is also proposed to modulate ovarian function during follicular waves in cattle and has potent inhibitory effects on follicular development. Polycystic ovary syndrome (PCOS), presenting itself with multiple follicular ovarian cysts, is the most common endocrinological disorder among women of reproductive age. Here we aimed to investigate the association of this peptide with PCOS. Our research was designed as a case-control study, in which a total of 148 subjects (73 with PCOS and 75 age- and BMI-matched CONTROLS) were consecutively recruited. Fasting blood glucose (FBG), insulin, high-sensitivity C-reactive protein, lipids, follicle stimulating hormone, luteinizing hormone, estradiol, CART, and free testosterone levels were measured in all participants. Homeostasis model assessment of insulin resistance (HOMA-IR) and body mass index (BMI) were calculated. CART levels were found to be significantly lower in patients with PCOS (PCOS: 90.77 ± 5.98 pg/ml, CONTROLS: 93.24 ± 8.17 pg/ml, p=0.038). Pearson's correlation analysis showed that CART was significantly and negatively correlated with BMI and waist circumference in both (PCOS and control) groups. In CONTROLS only, CART was positively correlated with insulin and HOMA-IR, and negatively correlated with FBG. Logistic regression analysis results are suggestive of a possible protective effect of CART against PCOS (OR: 0.94, 95% CI=0.888-0.997, p=0.038).

USE OF COVER CROPS FOR WEED SUPPRESSION IN HAZELNUT (CORYLUS AVELLANA L.) IN TURKEY.

Weed management is critical in hazelnut (Corylus avellana) production. Weeds reduce nutrient availability, interfere with tree growth, and reduce hand-harvesting efficiency. Field experiments were conducted to test effects of cover crops as alternative weed management strategies in hazelnut. The cover crop treatments consisted of Trifolium repens L., Festuca rubra subsp. rubra L., Festuca arundinacea Schreb., Vicia villosa Roth. And Trifolium meneghinianum Celmand fallow with no cover crop. Control plots such as weedy control, herbicide control and mechanical control were added as reference plots. The lowest weed dry biomass was obtained from Vicia villosa plots, and there were no significant differences among all other cover crop treatments. The highest cover crop dry biomass was measured in the Trifolium meneghinianum plots. Regarding the effect of cover crops on hazelnut yields, the lowest yield was ob- tained from weedy control plots, while the highest yield was obtained from F. arundinacea plots. This research indicated that cover crops could be used as living mulch in integrated weed management programs to manage weeds in the hazelnut orchards.

Buried and trapped penis: a case report.

While buried penis cases are characterised by congenital normal attachments to penis, trapped penis cases are characterised by insufficiency of penile skin occurring as a complication after surgical operations such as circumcision. Unless diagnosed, circumcision procedures should be avoided in congenital concealed penis cases. Here we present a case of congenital buried penis with deteriorated clinical findings after two circumcision procedures at 1.5 years of age. The surgical treatment applied in this case is discussed.

Adaptation process of the skin graft to vaginal mucosa after McIndoe vaginoplasty.

OBJECTIVE: There are many methods of treatment of vaginal agenesis. METHODS: In this study, patients who underwent McIndoe vaginoplasty were evaluated for development of vaginal mucosa. Vaginal pH measurements, smears, and punch biopsies were obtained from seven patients postoperatively at 3, 6, and 12 months after having McIndoe vaginoplasty. RESULTS: Neovaginal smears indicated no specific data for mucosal development at the 3rd and 6th month after the operation. However, Doderlein bacilli were determined at the 12th month. Histopathological examination of punch biopsies revealed dermal and subdermal thickening at the 3rd month, partial adaptation to mucosa at 6th month, and full adaptation to mucosa at 12th month. Also normal vaginal pH levels were recorded at the 12th month. CONCLUSION: As a result of the adaptation process, the split thickness skin graft acquired both histological and physiological characteristics of normal vaginal mucosa. Also, neovaginal epithelium was evaluated to be macroscopically similar to normal vaginal mucosa, 12 months after the operation.

The effects of cover crop on weed control in collard (Brassica olerecea var acephala) and lettuce (Lactuca sativa L.).

Leafy vegetables are not very competitive and weed interference can cause considerable yield losses in collard (Brassica olerecea var acephala) and lettuce (Lactuca sativa L.). Currently there are no pre or post emergence herbicides registered for weed control in these vegetables in Turkey. For this reason, alternative weed control strategies need to be developed. Cover crop residue could represent an alternative method of weed management in these crops. Field studies were conducted in 2004 at the Black Sea Agricultural Research Institute experimental field in Samsun, Turkey. The cover crop treatments consisted of Sorghum bicolor (L.) Moench, Sorghum vulgare Pers., Vicia villosa L., Amaranthus cruentus L., Pisum sativum L. and the bare ground with no cover crop. All cover crops were seeded by hand and incorporated into the soil on 11 May, 2004. Each plot was 10 m2 (2 x 5 m) and arranged in a randomized complete block design with four replications. All cover crops were incorporated into the soil by discing on 1 September 2004 at flowering stage of the cover crops. Broadleaved weed species were dominant in the experimental area. Most cover crops established well and S. bicolor biomass was the highest. The number of weed species emerging in all treatments was different at 14 DAD (days after desiccation). Similar results were observed at 28 and 56 DAD. Treatments with Vicia villosa residues had fewer weed species and lower total weed densities than other treatments.

[The use of real-time polymerase chain reaction and enzyme immunoassay for the diagnosis of acute parvovirus B19 infections in immunosuppressed patients]. / Immünsüpresif hastalarda akut parvovirus B19 enfeksiyonunun tanisinda enzim immún yóntemi ile gerçek zamanli polimeraz zincir reaksiyonunun kullanimi.

Human parvovirus B19 (PV-B19) infection may lead to very serious clinical situations such as transient aplastic crisis in patients with hemolytic anemia, thrombocytopenia, neutropenia and transient arthritis accompanied with erythema infectiosum, especially in immunosuppressed patients. Early diagnosis of PV-B19 infection is of critical importance especially in immunosuppressed patients since the necessary precautions can be undertaken accordingly. In this study, PV-B19 IgM and IgG antibodies and viral DNA have been searched by enzyme immunoassay (ELISA) and real-time polymerase chain reaction (PCR), respectively, in 50 PV-B19 suspected immunosuppressed patients. Viral IgM, IgG and DNA positivities were detected in 7 (14%), 20 (40%) and 7 (14%) of the patients, respectively. During the first week three patients were found DNA and IgM positive but IgG negative, while four patients were found positive for the viral DNA, IgM and IgGs. The DNA copy numbers were high in all of the patients during the first week, with a gradual decrease during a seven-week follow-up period. IgM antibodies have disappeared in the sixth week in three of the patients and at the end of the seventh week in four of the patients. Although the IgG antibodies were negative in three patients in the first week, they became positive in the second week and the titers gradually increased during the following weeks. According to the results of this study, it can be concluded that, in high risk groups such as immunosuppressed patients, in addition to ELISA, real-time PCR method would be helpful for the early diagnosis of PV-B19 infections.