Effect of the Combination of Exercise and Metformin on Osteocalcin, Insülin, Interleukin-6, Glucose Levels, and Body Weights in Rats.

BACKGROUND: Exercise or exercise capacity is a vital physiological function. It is known that certain cytokines support muscle function during exercise and, as a result, increase exercise capacity. AIMS: In this study, the effect of metformin administered in combination with exercise on osteocalcin (OCN), insulin, and interleukin-6 (IL-6) levels in rats was investigated. METHODS: Forty-two male Wistar rats were used in this study. The animals were randomly divided into six groups: control (CONT), only exercise (EXE), metformin_100 mg/kg (Met100), metformin_200 mg/kg (Met200), metformin_100 mg/kg+exercise (Met100+EXE), and metformin_200 mg/kg+exercise (Met200+EXE). A 10-week intervention was conducted, excluding exercise training. During the experiment, the groups receiving metformin application (100 or 200 mg/kg) were administered with metformin. At the end of the study, serum samples were collected from the rats to determine the levels of osteocalcin, insulin, and IL-6 using the enzyme-linked immunosorbent assay method. In addition, glucose levels and body weights were evaluated. GraphPad Prism was used for the analyses. RESULTS: The OCN and insulin levels of the Met100+EXE and Met200+EXE groups were found to be higher compared to the CONT, Met100, and Met200 groups (P < 0.05). The IL-6 level of the EXE group was determined to be higher than that of the CONT, Met100, and Met200 groups (P < 0.01). It was observed that both exercise and the individual or combined application of metformin resulted in lower blood glucose levels compared to the CONT group. The mean body weight of the EXE group was higher than that of the other groups. CONCLUSION: The combined application of metformin and exercise has increased osteocalcin and insulin levels compared to metformin application alone.

The Impact of Dose Rate on the Tumor Microenvironment Using Flattening-filter-free Beams.

AIMS: Recently, dose delivery technology has rapidly evolved with flattening filter-free beams (FFF), and the biological effects of high dose rates are a matter of interest. We hypothesized that FFF beams at different dose rates obtained with modern linear accelerators have different effects on the TME. MATERIALS AND METHODS: The B16-F10 melanoma syngeneic tumor model was established, and mice were randomized to 2 different doses (2 Gy and 10 Gy) and 3 different dose rates (1 Gy/min, 6 Gy/min, and 14 Gy/min) along with the control group. Euthanasia was performed on the seventh day after RT, and intracardiac blood was collected for a comet assay. Tumors were harvested and examined histomorphologically and immunohistochemically. Statistical analyses were performed using SPSS software version 23 (SPSS Inc., Chicago, IL, USA). RESULTS: The daily growth rate was uniform, and no difference was observed between tumor volumes across all three dose rates for each dose. Deoxyribonucleic acid (DNA) damage in blood mononuclear cells was not affected by dose or dose rate. In the TME histomorphological examination, the number of mitosis is less in the 10 Gy arm, whereas the pleomorphism score was greater. Nevertheless, varying dose rates had no effect on the number of mitosis or the pleomorphism score. The severity of the inflammation, cell densities in the TME, and expression of immunohistochemical markers were comparable across all doses and dose rates. CONCLUSION: In our study involving the B16-F10 syngeneic tumor model, varying dose rates obtained with FFF beams had no effect on tumor volume, blood mononuclear cell DNA damage, or TME parameters. However, in order to fully understand the biological impacts of novel techniques, our study should be validated with alternative preclinical setups.

Molecular cloning of the OMP19 gene from Brucella melitensis strain H38 and its antigenicity compared to that of commercial OMP19.

Brucellosis is a worldwide zoonosis, that can still be classified as endemic despite its ancient origins which causes economic losses and public health problems. Although effectively controlled by vaccination in animals, there is currently no vaccine for use in humans. Outer Membrane Proteins (OMP) that play an active immunogenic and protective role in the Brucellae family. OMP19 is present in all Brucella species as a surface antigen and is a potent immunogen responsible for Brucellosis intracellular infection. For this reason, the study was aimed to be used safely as a potential recombinant vaccine candidate against all Brucella infections, especially in humans and pregnant animals. This study evaluated a Brucella lipoprotein antigen, i.e. 19 kilodalton (kDa) outer membrane protein (OMP19), which was amplified and cloned into the pETSUMO vector system. The immunogenic power of the purified recombinant OMP19 antigen against brucellosis was compared with that of OMP19 (Raybiotech Inc, USA) in a mouse model and the obtained rOMP19 antigen was found to be similar to the commercially available recombinant protein.

Deceased Donor Kidney Transplantation in a Human Immunodeficiency Virus-Infected Recipient: A Case Report.

Human immunodeficiency virus (HIV) infection has traditionally been considered an absolute contraindication for transplantation because immunosuppression will accelerate the disease progression and increase mortality. New antiretroviral agents have given rise to new perspectives and transplantation practices. Now renal transplantation is the gold standard treatment for end-stage renal disease in HIV-infected patients, but increased rejection and toxicity rates and compliance with treatment are important issues. Therefore, patient selection and follow-up should be done carefully in this patient group. Here we present a 51-year-old, male, HIV-infected patient who was diagnosed with HIV at his routine serologic investigation at 2015. Highly active antiretroviral therapy was initiated. One haplotype-matched kidney transplantation from a deceased donor was performed on October 19, 2016. Induction therapy was not administered, and the immunosuppressive regimen included tacrolimus, mycophenolate mofetil, and prednisolone. After 26 months, serum creatinine was 1.1 mg/dL and proteinuria 0.1 g/day. There was no development of donor-specific antibodies. The patient's current HIV viral load remains undetectable (and had been the entire time post-transplantation) while his CD4+ T-cell count currently is 543/mm3.

Aggressive squamous cell carcinoma of the renal pelvis.

Squamous cell carcinoma (SCC) of the renal pelvis is a particularly rare tumor that accounts for a minor portion of renal malignancies and is aggressive with an unfavorable prognosis. It is usually diagnosed after surgery and at advanced stages as it does not possess specific clinical and radiological properties. The pathological examination of a 38-year-old female patient who had undergone nephrectomy due to a nonfunctioning right kidney caused by long-standing staghorn calculus revealed moderately differentiated renal pelvis SCC invading the renal parenchyma. The patient who experienced severe lumbar pain in the second postoperative month presented lymphadenopathy, which could not be detected with ultrasonography but was diagnosed with 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18FDG PET/CT). The patient received systemic treatment following the early diagnosis and survived past the average survival time. It was concluded that in cases where SCC was diagnosed after nephrectomy, investigating metastasis with 18FDG PET/CT and initiating early systemic treatment in the presence of metastasis could contribute to survival.

Temperature dependence of the current-voltage characteristics of Sn/PANI/p-Si/Al heterojunctions.

Sn/PANI/p-Si/Al heterojunctions were fabricated by electropolymerization of aniline on chemically cleaned p-Si substrates. Current-voltage characteristics of Sn/PANI/p-Si/Al heterojunctions measured in the temperature range 140-280 K are presented and analyzed. Although these devices were clearly rectifying, their I-V characteristics were non-ideal, which can be judged from the nonlinearity in the semi-logarithmic plots. The high values of the ideality factor n depending on the sample temperature may be ascribed to a decrease of the exponentially increasing rate in current due to space-charge injection into the PANI thin film at higher forward bias voltages. Careful analysis of the forward bias I-V characteristics on a log-log scale indicates that the space-charge-limited current (SCLC) conduction controlled by an exponential trap distribution above the valence band edge dominates the current transport in the PANI/p-Si diodes at high voltages. Furthermore, the PANI was characterized by using Fourier transform infrared (FTIR) and ultraviolet-visible (UV-vis) spectra.

Three-layer reconstruction with fascia lata and vascularized pericranium for anterior skull base defects.

BACKGROUND: We report an assessment of the efficiacy of a triple layer graft composed of fascia lata and vascularized pericranium for anterior skull base reconstruction. This technique is based on the concept that vascularized tissue over a free flap may promote vascularization and rapid wound healing. METHOD: A large fascial graft is prepared from the fascia lata and divided in two pieces and trimmed to a size larger than the bone and dural defect. Vascularized pericranium is harvested after bicoronal incision and elevating the bifrontal scalp flap down to the supraorbital rims. First is dural repair, which is performed with fascia lata placed between the brain and remaining dura. Second, fascia lata is placed over the skull base defect and secured with mini titanium screws over the cranial surface of the orbital ridges. Third, vascularized pericranium is laid between the two layers of fascia lata. FINDINGS: We studied 17 patients of whom 2 had malignancy, 6 had olfactory groove meningioma, 6 had skull base fracture and rhinorrhea, 1 case had orbital meningioma, 1 had invasive pituitary adenoma and 1 had basal encephalocele. The transbasal approach was used as a single procedure in 13 cases. The extended transbasal approach combined with a transfacial approach was used in 3 cases and with a pterional approach in 1 case. In each patient, reconstruction of the cranial base was performed with triple layer graft of fascia lata and vascularized pericranium. The patients were followed-up 2 months to 5 years. None of the patients experienced postoperative cerebrospinal fluid leakage, meningitis, abscess, brain herniation and tension pneumocephalus. INTERPRETATION: Fascia lata with vascularized pericranium is highly reliable, tensile and well suited for reconstruction of the anterior skull base.

Efficacy of methylprednisolone in acute experimental cauda equina injury.

In this experimental study the efficacy of methylprednisolone was investigated by neurophysiological and histopathological evaluation in a rabbit cauda equina model where injury was produced with an aneurysm clip (closed pressure 192 gr). High dose methylprednisolone (kg/30 mg) was administered by intravenous infusion in the 8th, 16th and 24th hours after injury followed by infusion of the same dosage every 6 hours for 24 hours. Nerve conduction velocity was measured before and early after trauma and 3 weeks after injury. Both neurophysiological and histopathological investigations demonstrated the neuroprotective effectiveness of methylprednisolone if it was given in the 8th hour after trauma. Although recovery was observed its efficacy was less pronounced when it was given in the 16th and 24th hours.

Penetration of topically applied ciprofloxacin, norfloxacin and ofloxacin into the aqueous humor of the uninflamed human eye.

This study was undertaken to compare aqueous humor penetration of topical 0.3% ciprofloxacin, 0.3% norfloxacin and 0.3% ofloxacin in 63 patients undergoing cataract surgery. The patients were divided into two groups. Group 1 (long-term treatment) involved 30 patients undergoing cataract extraction who received either 0.3% ciprofloxacin, 0.3% norfloxacin or 0.3% ofloxacin topical drops. Each patient was preoperatively given a single drop per hour six times. At the time of surgery, 0.1 ml aqueous fluid was aspirated from the anterior chamber and immediately stored at -70 degrees C. Topically applied ciprofloxacin, ofloxacin and norfloxacin achieved mean aqueous humor levels of 2.80 +/- 1.07, 2.95 +/- 1.19 and 1.50 +/- 0.48 micrograms/ml respectively. There was no statistically significant difference in intraocular mean aqueous levels of ciprofloxacin versus ofloxacin. Topical ciprofloxacin and ofloxacin achieved mean aqueous humor levels significantly higher than norfloxacin (p < 0.001 and p < 0.0008 respectively). Group 2 (short-term treatment) involved 33 patients undergoing cataract extraction who received 0.3% ciprofloxacin, 0.3% ofloxacin and 0.3% norfloxacin topical drops. These patients were given one drop at 90 minutes and one drop 30 minutes preoperatively. At the time of surgery, 0.1 ml aqueous fluid was aspirated from the anterior chamber and immediately stored at -70 degrees C. Topically applied ciprofloxacin, ofloxacin and norfloxacin achieved mean aqueous humor levels of 1.11 +/- 0.50, 1.50 +/- 0.62 and 1.20 +/- 0.43 micrograms/ml respectively. There was no statistically significant difference in intraocular mean aqueous humor levels of ofloxacin versus norfloxacin and ciprofloxacin versus norfloxacin. Topical ofloxacin achieved a significantly higher mean aqueous humor level than ciprofloxacin (p < 0.03). All levels were above the minimum inhibitory concentrations of ciprofloxacin, ofloxacin and norfloxacin for most of the sensitive organisms.

Comparative tear concentrations of topically applied ciprofloxacin, ofloxacin, and norfloxacin in human eyes.

The tear pharmacokinetic profiles of 0.3% ciprofloxacin, 0.3% ofloxacin, and 0.3% norfloxacin ophthalmic solutions after a single drop topically administrations in the eyes of 30 healthy volunteers were evaluated. Tear samples collected at 30, 120, 180, and 240 minutes, were analyzed for drug concentrations by high performance liquid chromatography (HPLC) with fluorometric detection. Topically applied ciprofloxacin, ofloxacin, and norfloxacin achieved the mean tear concentrations (mean +/- SD) of 11.28 +/- 6.98, 6.52 +/- 4.06, and 13.28 +/- 8.78 micrograms/g at 30 min, and then fell to 3.52 +/- 1.30, 4.82 +/- 1.80, and 5.79 +/- 4.80 micrograms/g at 240 min, respectively. Topical norfloxacin achieved mean tear level significantly higher than ofloxacin at 30 min (p = 0.031). There were no statistically significant differences in the mean tear levels of ciprofloxacin versus ofloxacin (at 30, 120, 180, and 240 min), ciprofloxacin versus norfloxacin (at 30, 120, 180, and 240 min) and ofloxacin versus norfloxacin (at 120, 180, and 240 min). However, the mean tear levels, 240 min after dosing ciprofloxacin and norfloxacin, fell to the statistically significant concentrations (p = 0.02 and p = 0.01, respectively). But, it is concluded that concentrations of ciprofloxacin, ofloxacin, and norfloxacin in tears were still significantly greater than the minimum inhibitory concentrations for the most sensitive organisms, 240 min after a single drop application.

Congenital cholesteatoma with spontaneous epidural abscess, sinus thrombosis and cutaneous fistula.

A congenital cholesteatoma or epidermoid is a benign mass that causes devastating effects if left untreated. An unusual case with a congenital cholesteatoma located in the mastoid region complicated by epidural abscess, sinus thrombosis, and cutaneous fistula is presented. The patient had normal otologic findings and had no neurologic deficit. A review of the literature found no report of a similar case.

Unusual malformations in occult spinal dysraphism.

Two cases of occult spinal dysraphism with different clinical symptoms, signs and congenital pathologies are presented. One had malformations including scoliosis, dermoid tumor, hydromyelia, diastematomyelia, dermal sinus, low conus, vertebrae anomalies and dextrocardia. The occurrence of dextrocardia in association with occult spinal dysraphism was found to be extremely unusual. The second case is presented in relation to the rarity of teratoma with dermal sinus and tethered cord in the lumbar area. Myelography, computed tomography, (CT), Myelo CT and magnetic resonance were used in making a diagnosis.

Experimental evaluation of peritoneum and pericardium as dural substitutes.

Although many substances have been tested in the search for an ideal dural substitute, an entirely satisfactory material has still not been found. The authors report an experimental study involving the closure of dural defects in rabbits with biomaterials developed from pig peritoneum and pericardium. Macroscopic and histologic examination, performed over a period between 15 and 45 days after implantation showed slight or no adhesion between the graft material and the cortex. No infection, CSF leakage, fistula or toxicity was noticed. The results demonstrated that these biomaterials could be used as satisfactory dural substitutes.

Surgical management of craniocerebral gunshot wounds.

Thirty-nine cases operated on because of gunshot wounds in our clinics the years 1976-1986 have been investigated. Factors contributing to mortality and outcome were evaluated. All the principles of emergency medical care and of surgical treatment of penetrating wounds should be applied to those patients with craniocerebral gunshot wounds in whom surgery is indicated.

An experimental evaluation of response to contrast media: Pantopaque, iopamidol, and iohexol in the subarachnoid space.

Myelography in dogs was performed with Pantopaque, iopamidol and iohexol. The effects of these agents were evaluated by histologic study of the brain, spinal cord, and meninges four months after the procedure. Retained Pantopaque was always accompanied by some degree of arachnoidal reaction, mild in the cervical cord segment and severe in the most caudal part of the cul-de-sac. No apparent protection against Pantopaque arachnoiditis was provided by either intrathecal or intramuscular methylprednisolone. We found no histologic evidence of arachnoiditis in animals examined with iopamidol and iohexol.