Daidzein nanosuspension in combination with cisplatin to enhance therapeutic efficacy against A549 non-small lung cancer cells: an in vitro evaluation.

Lung cancer is the most common cause of cancer-related mortality, chemo-resistance, and toxicity limit treatment. The focus is on innovative combined phytotherapy to improve treatment outcomes. Our aim was to investigate the potential effects of daidzein nanosuspension (DZ-NS) and its combination with cisplatin (CIS) on A549 non-small lung cancer cells. Cytotoxicity was investigated using MTT and Chou-Talalay methods. Oxidative, apoptotic, and inflammatory markers were analyzed by ELISA and qRT-PCR. The IC50 value for DZ-NS was 25.23 µM for 24 h and was lower than pure DZ (IC50 = 835 µM for pure DZ). DZ-NS (at IC50x2 and IC50 values) showed synergistic cytotoxicity with CIS. The cells treated with DZ-NS had low TOS and OSI levels. However, DZ-NS failed to regulate Cas3 and TGF-ß1 activation in A549 cells. MMP-9 gene expression was significantly suppressed in DZ-NS-treated cells, especially in combination therapy. DZ represents a potential combination option for the treatment of lung cancer, and its poor toxicokinetic properties limit its clinical use. To overcome these limitations, the effects of the nanosuspension formulation were tested. DZ-NS showed a cytotoxic effect on A549 cells and optimized the therapeutic effect of CIS. This in vitro synergistic effect was mediated by suppression of MMP-9 and not by oxidative stress or Cas3-activated apoptosis. This study provides the basis for an in vivo and clinical trial of DZ-NS with concurrent chemotherapy.

Outcomes of high-risk breast lesions diagnosed using image-guided core needle biopsy: results from a multicenter retrospective study.

PURPOSE: The clinical management of high-risk lesions using image-guided biopsy is challenging. This study aimed to evaluate the rates at which such lesions were upgraded to malignancy and identify possible predictive factors for upgrading high-risk lesions. METHODS: This retrospective multicenter analysis included 1.343 patients diagnosed with high-risk lesions using an image-guided core needle or vacuum-assisted biopsy (VAB). Only patients managed using an excisional biopsy or with at least one year of documented radiological follow-up were included. For each, the Breast Imaging Reporting and Data System (BI-RADS) category, number of samples, needle thickness, and lesion size were correlated with malignancy upgrade rates in different histologic subtypes. Pearson's chi-squared test, the Fisher-Freeman-Halton test, and Fisher's exact test were used for the statistical analyses. RESULTS: The overall upgrade rate was 20.6%, with the highest rates in the subtypes of intraductal papilloma (IP) with atypia (44.7%; 55/123), followed by atypical ductal hyperplasia (ADH) (38.4%; 144/375), lobular neoplasia (LN) (12.7%; 7/55), papilloma without atypia (9.4%; 58/611), flat epithelial atypia (FEA) (8.7%; 10/114), and radial scars (RSs) (4.6%; 3/65). There was a significant relationship between the upgrade rate and BI-RADS category, number of samples, and lesion size Lesion size was the most predictive factor for an upgrade in all subtypes. CONCLUSION: ADH and atypical IP showed considerable upgrade rates to malignancy, requiring surgical excision. The LN, IP without atypia, pure FEA, and RS subtypes showed lower malignancy rates when the BI-RADS category was lower and in smaller lesions that had been adequately sampled using VAB. After being discussed in a multidisciplinary meeting, these cases could be managed with follow-up instead of excision.

In Vivo Evaluation of Nanoemulsion Formulations for Metformin and Repaglinide Alone and Combination.

Repaglinide and Metformin are used to treat Type 2 diabetes. Repaglinide with poor water solubility has relatively low oral bioavailability (56%) and undergoes hepatic first-pass metabolism. The oral bioavailability of metformin HCl is also low (about 50-60%). The purpose of this study was to prepare nanoemulsion formulations containing metformin HCl or repaglinide alone or in combination and characterize them in vitro and in vivo. Nanoemulsion formulations containing metformin HCl and/or repaglinide were successfully prepared and in vitro characterized. In addition, in vivo efficacy of nanoemulsion formulations was evaluated in a streptozotocin-nicotinamide-induced diabetic rat model. Biochemical, histopathological, and immunohistochemical evaluations were also performed. The mean droplet size and zeta potential values of nanoemulsion formulations were in the range of 110.15±2.64-120.23±2.16 nm and -21.95 - -24.33 mV, respectively. The percent entrapment efficiency values of nanoemulsion formulations were in the range of 93.600%-96.152%. All nanoemulsion formulations had a PDI of ≤0.223. A statistically significant decrease was observed in the blood glucose values of the diabetic rats treated with nanoemulsion formulations containing active substance/substances, compared to diabetic rats (control) (p<0.05). Nanoemulsion formulations (especially nanoemulsion containing metformin HCl and repaglinide combination) have a better antidiabetic activity and are more effective in reducing oxidative stress caused by diabetes.

The Nanosuspension Formulations of Daidzein: Preparation and In Vitro Characterization

Objectives: Daidzein (DZ), a water-insoluble isoflavone, has many beneficial effects (anti-inflammatory, antioxidant, and anticancer effects, etc.) on human health. DZ has a very low oral bioavailability related to its physicochemical properties (low solubility, intense metabolism of DZ in the intestine and liver). This study aimed to prepare and in vitro characterize the nanosuspension formulations of DZ to improve the poor solubility and efficacy of DZ. Materials and Methods: DZ nanosuspension formulations were prepared with media milling technique using zirconium oxide beads as milling media. Pluronic F127 and polyvinylpyrrolidone (PVP) K30 (formulation A; F-A) and sodium dodecyl sulfate (SDS) (SDS + pluronic F127 + PVP K30; formulation B; F-B) were used as stabilizers. The nanosuspension formulations were evaluated for morphological properties, particle sizes, zeta potential, DZ content, saturation solubility, dissolution, and their cytotoxic effects on RG2 glioblastoma tumor cells. Results: F-A and F-B formulations were nanosized (in the range of about 181-235 nm) and had negative zeta potential values before and after lyophilization. The DZ content of F-A and F-B formulations were found to be 93.68±0.78% and 89.75±0.49%, respectively. Fourier transform infrared spectroscopy analysis showed that there was no significant interaction between DZ and the excipients. Differential scanning calorimetry and X-ray diffraction analyses confirmed no change in the crystal structure of DZ in F-A and F-B formulations. Conclusion: In this study, the nanosuspension formulations were successfully prepared and characterized in vitro. Nanosuspension formulations increased the saturation solubility, dissolution rate, and cytotoxic effect of DZ.

Assessment of Pharmacokinetic Parameters of Daidzein-Containing Nanosuspension and Nanoemulsion Formulations After Oral Administration to Rats.

BACKGROUND AND OBJECTIVES: Daidzein has several biological effects such as antioxidation, anti-inflammation, chemoprevention, and anticancer effects. The aim of this study was to evaluate the impact of nano-formulations (nanoemulsion-NE and nanosuspension-NS) prepared to increase the oral bioavailability of daidzein, a poorly water-soluble isoflavone, on the pharmacokinetic parameters of daidzein in rats. METHODS: A high-performance liquid chromatography-ultraviolet (HPLC-UV) method was successfully developed for daidzein analysis in rat plasma. The pharmacokinetics studies of the nano-sized formulations, compared to coarse daidzein suspension, were carried out in the rats by a single oral dose at 10 mg/kg (n = 6/group). Area under the plasma concentration-time curve from time zero to extrapolation to time infinity (AUC0-∞), maximum plasma concentration (Cmax), time to reach maximum plasma concentration (tmax), and elimination half life (t1/2) values for coarse daidzein suspension, daidzein-NS, and daidzein-NE were estimated by a non-compartmental analysis. RESULTS: The AUC values of daidzein-NE and daidzein-NS were approximately 2.62 and 2.65 times higher than that of coarse daidzein suspension, respectively (p < 0.05). Relative bioavailability (Frel) (%) values of daidzein following oral administration of nanosuspension or nanoemulsion formulations were about 265.6% and 262.3%, respectively. CONCLUSION: It revealed that nanoscale size is an important factor to overcome any dissolution rate barriers to oral bioavailability of the low water-soluble compound. Nanoemulsion and nanosuspension formulations are beneficial dosage forms to increase the oral bioavailability of Biopharmaceutical Classification System (BCS) Class II and Class IV compounds.

The Evaluation of the Effects of Nanoemulsion Formulations Containing Boron and/or Zinc on the Wound Healing in Diabetic Rats.

Wound healing remains a challenging clinical problem, especially in the presence of diabetes. Diabetic patients have the impaired ability to fight infection and insufficient inflammatory response. The aim of this study was to evaluate the effects of boronophenylalanine (BFA) and/or Zn-containing nanoemulsion (NE) formulations on wound healing in diabetic rats. MTT and scratch assays were performed to evaluate the proliferative effects of BFA and/or Zn on human dermal fibroblast (HDF) cells and the migration of these cells, respectively. The BFA and/or Zn-NE were prepared, and the effects of NEs on wound healing in diabetic rats were evaluated by applying once a day for 14 days. MTT assay showed that 10 to 25 µM BFA and/or 50 µM Zn had very significant positive effects on cell proliferation. In the scratch assay, 10 µM BFA significantly increased the migration of HDF cell compared with control. The droplet sizes of all the NEs were <115 nm and their zeta potential values were in range of (-) 23.9 ± 2.356 to (-) 33.1 ± 1.438 mV. There was a significant reduction in the wound contraction values (%) of the groups treated with the BFA and/or Zn-NE on the 14th day compared with the untreated diabetic rats group. According to histopathological findings, wound healing was nearly complete in BFA and/or Zn-NE compared with untreated diabetic rats. Especially, the group treated with the NE containing the low concentration of BFA showed highly promising results in wound healing of diabetic rats within 14 days with complete epithelialization and the completely closed wound area.

Orally disintegrating tablet containing carbamazepine and levetiracetam: formulation and in vitro and in vivo characterization.

This study aimed to prepare and characterize the orally disintegrating tablet (ODT) formulations containing the combination of levetiracetam (LEV) and carbamazepine (CBZ) (CBZ + LEV combination) for the treatment of epilepsy. The ODT formulations were prepared using the lyophilization (L) and direct compression (DC) methods. The flowability of the mixed powders used for DC formulation was evaluated. The quality control tests for the ODTs were performed. Also, the antiepileptic effects of pure drugs, their combination, and the suspension of CBZ + LEV-DC-ODT formulation were evaluated in the rats with pentylenetetrazole (PTZ)-induced epilepsy model. The obtained results for the mixed powders of the DC formulation (angle of repose: 26.18 ± 0.794°; compressibility index: 15.24 ± 0.764%) suggest that the flow properties of the powder blend were suitable for the preparation of CBZ + LEV-ODT using DC method. The mean values of diameter and hardness of L-ODTs and DC-ODTs were found to be 16.87 mm and 16.18 mm and 11.96 N and 30.11 N, respectively. The friability of both formulations was <1%. Both formulations were disintegrated in seconds. Drugs in L-ODT had faster dissolution than those in DC-ODT. Compared to the seizure scores obtained for the groups treated with LEV or CBZ, generally, there was a higher decrease in seizure scores in the groups treated with CBZ + LEV combination or the suspension of CBZ + LEV-DC-ODTs. Consequently, the ODT formulations containing the CBZ + LEV combination might be beneficial in the treatment of epilepsy.

Effects of Emulsion Formulations of Oleuropein Isolated from Ethanol Extract of Olive Leaf in Diabetic Rats.

This study was designed to investigate the effects of emulsion formulations of oleuropein isolated from ethanol extract of olive leaf in streptozotocin-diabetic rats. The rats were treated with the administration of the emulsion containing oleuropein at a low (150 mg/kg b.wt.) and high (225 mg/kg b.wt.) dose for 30 days. At the end of the study, blood samples were drawn from the heart of the rats to determine blood glucose, alanine transaminase, and aspartate transaminase levels. In addition, their liver tissues were dissected to determine the levels of glutathione and thiobarbituric acid-reactive substances, and superoxide dismutase activity. According to the results for both dose treatments, a statistically significant increase in superoxide dismutase activities and glutathione levels of the treated diabetic rats was observed when compared with those of the diabetic control rats. On the other hand, a statistically significant decrease in the levels of thiobarbituric acid-reactive substances, aspartate transaminase and alanine transaminase of the treated diabetic rats was determined. It should be highlighted that the administrations at the high dose were more effective compared to that of the low dose. Furthermore, a substantial decrease in the blood glucose levels of the diabetic rats exposed to the high dose was observed.

Development and characterization of metformin hydrochloride- and glyburide-containing orally disintegrating tablets.

Diabetes is characterized by chronic hyperglycemia. Although metformin hydrochloride (MHCl)- and glyburide (GLB)-containing conventional tablets are available in the market and used to treat diabetes, orally disintegrating tablets (ODTs) containing the combination of these drugs are not commercially available. Therefore, the aim of this study was to prepare ODTs containing MHCl and GLB by direct-compression (DC-ODTs) and freeze-drying (FD-ODTs) methods. Physical properties of the powder mixture of DC-ODT formulation were determined (Angle of repose: 37.18 ± 1.27°; compressibility index: 20.31 ± 1.06%; Hausner ratio: 1.25 ± 0.03). Its moisture content was 0.3 ± 0.09%. The hardness values and the disintegration times for DC-ODTs and FD-ODTs were 221.60 ± 40.82 and 66.54 ± 2.68 N, and 80 and 30 s, respectively. Friability values were 0.24% for DC-ODTs and 0.38% for FD-ODTs. In uniformity-of-mass for single-dose-preparations test, the average weight was 684.38 ± 1.97 mg for DC-ODTs and 342.93 ± 2.4 mg for FD-ODTs, with less than 5% deviation for all 20 tablets. Water-absorption ratio for DC-ODTs was 1.30 ± 0.05. More than 90% of MHCl and GLB were dissolved within 5 min in both DC-ODTs and FD-ODTs. Although Caco-2 permeability of MHCl was influenced by the ODTs, GLB permeability was not. These results indicated that MHCl- and GLB-containing ODTs may be used as promising formulations for the treatment of diabetes.

Carbamazepine and levetiracetam-loaded PLGA nanoparticles prepared by nanoprecipitation method: in vitro and in vivo studies.

Objective: The aim of this study was to develop the PLGA nanoparticles (NPs) containing carbamazepine (CBZ) and levetiracetam (LEV) combination (CBZ + LEV) for the treatment of epilepsy and to in vitro characterize the prepared NPs.Significance: LEV and CBZ, which are antiepileptic drugs, are used in the treatment of epilepsy. Nano-sized formulations are prepared to use for different purposes such as to improve the solubility/the physicochemical properties and bioavailability of drugs, to decrease their doses and frequency of administration, and to reduce side effects of drugs.Methods: CBZ + LEV-PLGA-NPs were prepared by a modified nanoprecipitation method and in vitro and in vivo characterized. Also, the antiepileptic effect of the NPs was evaluated in vivo in a rat epilepsy model.Results: The mean particle size and zeta potential of CBZ + LEV-PLGA-NPs were 180.62 ± 6.260 nm and -27.08 ± 3.110 mV, respectively. The values of encapsulation efficiency (EE%) of CBZ and LEV were 51.00 ± 5.944% and 2.05 ± 0.367%, respectively. CBZ showed a biphasic release profile with initial burst release followed by a sustained release. Ninety percent of CBZ was released from NPs within two days; however, % LEV release from NPs reached about 80% within 30 min.Conclusion: Our results showed that a decrease in seizure scores in the group treated with CBZ + LEV was observed and also, CBZ + LEV and CBZ + LEV-PLGA-NPs had similar antiepileptic activity. The NPs containing CBZ + LEV might be beneficial in the treatment of epilepsy.

Investigation of the efficacy of daidzein in experimental knee osteoarthritis-induced with monosodium iodoacetate in rats.

BACKGROUND: Osteoarthritis (OA) is a degenerative chronic illness that most frequently occurs in the knee joint. Daidzein (DZ) an isoflavone has anti-inflammatory and antioxidant activity. The aim of this study was to evaluate the effectiveness of DZ as a treatment for experimental knee OA (KOA) in rats. METHOD: An experimental KOA model was induced by monosodium iodoacetate (MIA) in rats. Thereafter, 49 Wistar albino male rats (250-300 g, 12-16 weeks old) were randomly divided into 7 groups: C (healthy control); DC (KOA + saline); hyaluronic acid (HA); HA+ intraarticular (ia) DZ; oral (po) DZ; ia DZ; HA + po DZ groups. DZ and/or HA were administered intraarticularly to the rats as 50 µL on days 1, 7, 14, and 21. Alternatively, the DZ was administered orally as 0.5 mL twice daily for 21 days. After the treatment, rats were sacrificed by decapitation under general anesthesia. Serum samples were analyzed to determine the total oxidant status (TOS) and total antioxidant status (TAS) and the levels of TNF-α, IL-1ß, MMP-13, and DZ. Knee joint samples underwent histopathological examination, and TNF-α, IL-1ß, NOS2, and MMP-13 were analyzed with immunohistochemical methods. RESULTS: HA, DZ, and DZ + HA effectively reduced the levels of TNF-α, IL-1ß, and MMP-13 in the serum of the DC group (p < 0.001). In groups that received HA, DZ, or DZ + HA, the serum TAS increased compared with the DC group (p < 0.05). When the DZ + HA combination was used, a more pronounced reduction in the levels of TNFα, NOS2, IL-1ß, and MMP-13 was observed in knee joints. In addition, the cracks on the cartilage surface and fibrillation were completely improved in the groups that received HA, DZ, or DZ + HA compared with the DC group. CONCLUSION: DZ had anti-inflammatory and antioxidant effects in a rat OA model. Therefore, DZ, as monotherapy or especially in combination with HA, may be a promising and beneficial therapy for OA. Key Points •DZ has been shown to reduce TNF-α, IL-1ß, and MMP-13 both in serum and in tissue samples taken from the knee-joints. •The cracks on the cartilage surface and fibrillation in KOA were completely improved by using DZ and DZ + HA combination. •DZ may be useful to eliminate/reduce/ameliorate inflammation and oxidative damage in the pathogenesis of KOA. •DZ, alone or in combination with HA, may be a promising natural compound with beneficial effects in the treatment of KOA.

The cytotoxic and genotoxic effects of daidzein on MIA PaCa-2 human pancreatic carcinoma cells and HT-29 human colon cancer cells.

Daidzein (DZ) has anti-inflammatory and antioxidant effects, as well as the dose-dependent inhibition effect on cancer cells. In this study, the cytotoxic and genotoxic effects of DZ on HT-29 (human colorectal adenocarcinoma cells) and MIA PaCa-2 (human pancreatic cancer cells) cell lines were determined using the XTT method and Comet assay, respectively. IC50 concentrations of DZ were found to be 200 µM in both MIA PaCa-2 and HT-29 cells treated with DZ for 48 hours (h). When the cells were treated with 200 µM of DZ for 48 h, DNA damage was observed in both cell lines. DNA tail length (TL), tail moment (TM), and tail intensity (TI) increased more in MIA PaCa-2 cells treated with 200 µM of DZ than those in the control cell (untreated MIA PaCa-2 cell) group (p < 0.01). However, only DNA-TI and DNA-TM exhibited higher increases in HT-29 cells treated with 200 µM of DZ than those in the control cell (untreated HT-29 cell) group (p < 0.01). This shows that DZ has cytotoxic and genotoxic effects on both cell lines. The observed genotoxic effects of DZ still need to be confirmed in additional future studies.

Radiological assessment of the lateral osteotomy line-lacrimal system distance on three-dimensional models.

AIMS: One of the most commonly performed operations in aesthetic, plastic, and reconstructive surgery is rhinoplasty, the aim of which is to construct an altered nasal shape, either for aesthetic or functional reasons. The lateral osteotomy is the most traumatic step of rhinoplasty, and is generally difficult to perform. The lacrimal system can be damaged during the lateral osteotomy procedure. In this study, we aimed to measure the distance between the lacrimal system and the lateral osteotomy line, and to determine the safe and ideal osteotomy level, which is very important in rhinoplasty procedures. We also evaluated the safe relationship of this osteotomy level with the lacrimal system by constructing a three-dimensional model. MATERIALS AND METHODS: The three-dimensional models were constructed on axial planes using paranasal computed tomographic (CT) images of 40 male and 40 female patients. The 'lateral osteotomy model' was designed in three dimensions. The axial CT images were obtained from the model. On the CT images, the distance between the lateral osteotomy line and the lacrimal system was assessed by measuring three distances. The first was the distance between the anterior lacrimal crest and the lateral osteotomy line. The second was the distance from the midpoint between the anterior lacrimal crest and the inferior meatus to the lateral osteotomy line. The third was the distance between the opening of the lacrimal canal to the inferior meatus and the lateral osteotomy line. RESULTS: No lacrimal system injury was seen on any of the models. The shortest distance was found between the anterior lacrimal crest and the lateral osteotomy line, measured at 4.5 mm and 5.0 mm in the female and male patients, respectively. CONCLUSION: Performing the lateral osteotomy meticulously while paying attention to remaining anterior to the medial canthal ligament will not lead to any lacrimal system injury.

Nifedipine-loaded polymeric nanoparticles: Preparation and in vitro characterization.

The purpose of the current study was to prepare nifedipine (NF) loaded-PLGA nanoparticles (NPs) using two different methods (nanoprecipitation method (N-2) and emulsion-solvent evaporation method (N-4)) to achieve the sustained release of NF and to reduce its side effects, and also to investigate the in vitro characteristics of NPs (surface morphology, particle size and size distribution, encapsulation efficiency and in vitro release characteristics). SEM images of nanoparticles revealed their approximate spherical shape. The mean particle sizes of the prepared nanoparticles ranged from 294.27±7.93 to 424.92±4.96 nm with almost neutral zeta potential values (close to 0 mV). The percent encapsulation efficiency values of N-2 and N-4 formulations 13.03±1.82% and 18.96±1.95% (p=0.05), respectively. The extents of cumulative drug release from N-2 and N-4 in PB pH 7.4 medium were up to about 100 % in 38 days and 22 days, respectively (when comparing two formulations, p<0.05). PLGA nanoparticles are useful systems for the sustained release of NF, and hence for reducing its side-effects and increasing patient compliance.

Effect of metformin/irinotecan-loaded poly-lactic-co-glycolic acid nanoparticles on glioblastoma: in vitro and in vivo studies.

AIM: The present study was designed to evaluate the effects of irinotecan hydrochloride (IRI)- or metformin hydrochloride (MET)-loaded poly-lactic-co-glycolic acid (PLGA) nanoparticles (NPs) for the treatment of glioblastoma multiforme using in vitro neuron and U-87 MG glioblastoma cell cultures and in vivo animal model. METHODS: The cytotoxic and neurotoxic effects of pure drugs, blank NPs and MET- and IRI-loaded PLGA NPs were investigated in vitro (using methylthiazolyldiphenyl-tetrazolium bromide assay) and in vivo (using Cavalieri's principle for estimation of cancer volume). RESULTS: 1 and 2 mM doses of MET and MET-loaded PLGA NPs, respectively, significantly reduced the volume of extracted cancer. CONCLUSION: Consequently, MET- and IRI-loaded PLGA NPs may be a promising approach for the treatment of glioblastoma multiforme.

Evaluation of the association between HIF-1α and HER-2 expression, hormone receptor status, Ki-67 expression, histology and tumor FDG uptake in breast cancer.

The present study aimed to examine hypoxia-inducible factor (HIF)-1α expression and its association with glucose uptake in invasive breast cancer. In addition, connections between glucose uptake and several other prognostic parameters of breast cancer were studied. Between August 2013 and April 2015, 92 patients with biopsy-diagnosed breast cancer were subjected to 18F-fluorodeoxyglucose positron emission tomography/computed tomography. The primary tumor and nodal maximum standardized uptake values (SUVmax) were recorded, and HIF-1α expression and clinical parameters, including tumor mass, estrogen receptor (ER) and progesterone receptor (PgR) levels, human epidermal growth factor receptor-2 (HER-2), Ki-67 index, grade and histology, were analyzed. SUVmax was compared with clinicopathological parameters and HIF-1α expression. The median SUVmax values of the ER-negative and PgR-negative tumors were significantly increased compared with ER and PgR-positive tumors, respectively (P=0.004 and P=0.008). SUVmax differed significantly between the T2 and T3 tumors and the T1 tumors. The median SUVmax levels were higher in the Ki-67 expression >10% group than the Ki-67 index <10% group (P=0.001). Although the median SUVmax values in HER-2-positive and -negative tumors were similar, triple-negative tumors demonstrated significantly higher values (P=0.04). With regard to tumor grade, the median SUVmax was greater in the high-grade tumors compared with the low-grade tumors. SUVmax did not exhibit a significant correlation with HIF-1α expression; however, HIF-1α expression was associated with tumor size and PgR expression. HIF-1α expression increased with a larger tumor size (r=0.27; P=0.008) and decreased PgR expression (r=-0.26; P=0.0002). The axillary nodal SUVmax of the N1 tumors was significantly lower than the N2 and N3 tumors (P<0.0001). In the multivariate analysis, tumor size, Ki-67 expression and ER Allred score were independent factors that impacted SUVmax. The results of the present study indicated strong associations between tumor size, tumor grade, Ki-67 expression, triple-negativity, downregulated hormone receptor expression and SUVmax values. Conversely, there was no association observed between glucose uptake and levels of HIF-1α. Based on these results, it is suggested that the lack of assiocation between hypoxia and glucose uptake indicates phenotypic independence.

Microparticulate and nanoparticulate drug delivery systems for metformin hydrochloride.

CONTEXT: Metformin hydrochloride is a biguanide derivative widely used for the treatment of type 2 diabetes, prescribed nearly to 120 million people worldwide. Metformin has a relatively low oral bioavailability (about 50-60%). Although the major effect of metformin is to decrease hepatic glucose output as an antihyperglycemic agent, its inhibitory effects on the proliferation of some cancer cells (e.g. prostate, breast, glioma cells) have been demonstrated in the cell culture studies. Development of novel formulation (e.g. microparticles, nanoparticles) strategies for metformin might be useful to improve its bioavailability, to reduce the dosing frequency, to decrease gastrointestinal side effects and toxicity and to be helpful for effective use of metformin in cancer treatment. OBJECTIVE: The main aim of this review is to summarize metformin HCl-loaded micro- and nanoparticulate drug delivery systems. METHOD: The literature was rewieved with regard to the physicochemical, pharmacological properties of metformin, and also its mechanism of action in type 2 diabetes and cancer. In addition, micro- and nanoparticulate drug delivery systems developed for metformin were gathered from the literature and the results were discussed. CONCLUSION: Metformin is an oral antihyperglycemic agent and also has potential antitumorigenic effects. The repeated applications of high doses of metformin (as immediate release formulations) are needed for an effective treatment due to its low oral bioavailability and short biological half-life. Drug delivery systems are very useful systems to overcome the difficulties associated with conventional dosage forms of metformin and also for its effective use in cancer treatment.

Transthoracic biopsy of lung masses: Non technical factors affecting complication occurrence.

BACKGROUND: To investigate the transthoracic computed tomography (CT)-guided lung nodule biopsy complications and risk factors associated with the development of these complications. METHODS: We retrospectively evaluated a total of 41 CT-guided transthoracic biopsy complications. Data was analyzed by chi-square and independent sample t-tests. RESULTS: Twenty-seven patients (28.7%) developed pneumothorax and eight patients (8.5%) developed parenchymal hemorrhage, and four patients (4.3%) hemothorax and two (2.1%) patients developed subcutaneous emphysema. A significant correlation was obtained between the development of pneumothorax and lesion size (P = 0.040), and the distance that traversed the parenchyma (P = 0.001). There was a statistically significant difference between the parenchymal hemorrhage and lesion size and the distance from passed parenchyma (P values were 0.021 and 0.008, respectively). An increased incidence of parenchymal hemorrhage and pneumothorax was observed at small size and deep-seated lesions. CONCLUSION: Lesion size and the distance that traversed the parenchyma on the biopsy tract are the most important factors that influence the development of complications in CT-guided transthoracic biopsy.

Anti TNF-α therapy might be responsible for an increased incidence of varicocele in patients with ankylosing spondylitis.

AIM: To evaluate the effects of anti-tumor necrosis factor-alpha (TNF-α) therapy on the frequency of varicocele in patients with ankylosing spondylitis (AS) using color Doppler ultrasound. MATERIALS AND METHODS: The patients were divided into 2 groups: patients with AS who were on anti-TNF-α treatment and patients with AS who were not regularly taking any antiinflammatory drugs. Thirty-one healthy volunteers were included as controls. RESULTS: Left-sided varicocele was determined in 14 patients of Group 1 (44%), 10 patients of Group 2 (33%), and 7 of the controls (23%). There was a statistically significant difference only between Group 1 and controls (P = 0.009). However, right-sided varicocele was determined in 12 patients of Group 1 (38%), 2 patients of Group 2 (6%), and 2 of the controls (6%) (P = 0.01 vs. Group 2, P = 0.005 vs. controls). CONCLUSION: The present study shows that patients with AS who were taking anti-TNF-a therapy had an increased prevalence of right- sided and bilateral varicocele compared to patients with AS who were not taking any disease-modifying antirheumatic drugs and the healthy control group.

Chitosan-poly (lactide-co-glycolide) (CS-PLGA) nanoparticles containing metformin HCl: preparation and in vitro evaluation.

In this study, the preparation and in vitro characterisation of metformin HCl-loaded CS-PLGA nanoparticles (NPs) were aimed. The prepared nanoparticles (blank nanoparticles (C-1), 50 mg of metformin HCl loaded nanoparticles (C-2) and 75 mg of metformin HCl loaded nanoparticles (C-3) ranged in size from 506.67±13.61 to 516.33±16.85 nm and had surface charges of 22.57±1.21 to 32.37±0.57 mV. Low encapsulation efficiency was observed for both nanoparticle formulations due to the leakage of metformin HCl to the external medium during preparation of nanoparticles. Nanoparticle formulations showed highly reproducible drug release profiles. ~20% of metformin HCl was released within 30 minutes and approximately 98% of the loaded metformin HCl was released at 144 hours in a phosphate buffer (PB; pH 6.8). No statistically significant difference was noted between the in vitro release profiles of the nanoparticles (C-2 and C-3) containing metformin HCl. Also, nanoparticles were characterised using FT-IR and DSC.