Acute effects of caffeine on choroidal thickness and ocular pulse amplitude

Objective: To explore ocular changes in healthy people after caffeine consumption.

Methods: This prospective observational study was carried out with students of the Turgut Özal University Medical Faculty from May 15 to 15 December 2014. Enrolled in the study were 17 healthy subjects (n?=?17 eyes), with a median age of 24 (IQR 1), ranging between 21 and 26 years. The control group (6 females, 11 males) aged between 23 and 28 (median 25 years [IQR 4.75]). For study, one eye from each participant was randomly selected. To obviate the effect of diurnal variations, tests were performed at the same time of the day (10:00?a.m.–12:00?p.m.). Each subject was given an ophthalmologic examination before the study to exclude those with undiagnosed ocular disease. Version 6.0 Cirrus high-definition optical coherence tomography (HD-OCT) (Carl Zeiss Meditec, Dublin, CA) was used to measure CT at the fovea, and 1500?μm nasal and 1500?μm temporal to the fovea. After baseline OCT measurements, participants were asked to have 200?mg oral caffeine intake or a placebo capsule (200?mg lactose powder). Two further OCT measurements were applied at the first and fourth hours of caffeine intake. All participants also had intraocular pressure (IOP) and ocular pulse amplitude (OPA) measurements recorded before, first and fourth hours of caffeine intake. IOP and OPA were measured using the dynamic contour tonometry (DCT) (Swiss Micro Technology AG, Port, Switzerland).

Results: The groups showed no significant difference by means of age, gender, spherical refraction and axial length (p?>?0.05). Baseline choroidal thickness measurements of the study and control group showed no significant difference. Oral caffeine intake caused a significant reduction in choroidal thickness compared with baseline, at all three measurement points, (p?<?0.05). There were no significant changes in IOP and OPA measurements compared with the baseline values (p?>?0.05). The choroidal thickness still continued to decrease for at least 4?h following caffeine intake; whereas, the difference between 1 and 4?h was not statistically significant (p?>?0.05). However, choroidal thicknesses, IOP and OPA values of the control group revealed no significant difference at all points when comparing measurements at baseline with 1 and 4?h after placebo intake (p?>?0.05).

Conclusions: We found no significant change in IOP and OPA following oral 200?mg caffeine intake, while CT significantly decreased, for at least 4?h.     

The long-term effect of oral isotretinoin therapy on macula ganglion cell complex thickness

Purpose: To evaluate the long-term effect of oral isotretinoin therapy on macula ganglion cell complex (GCC) thickness by spectral domain optical coherence tomography (SD-OCT).

Materials and methods: Newly diagnosed cystic acne patients who received low dose for a long time systemic isotretinoin therapy were included in this study. Thorough ophthalmic evaluation and GCC thickness analysis by using SD-OCT were performed at baseline, and at 1, 3, 6, and 12 months of treatment.

Results: Forty-eight eyes of 24 patients (15 females, 9 males) were included in the study. The mean age of patients was 19.37?±?2.74 years (range 14–25 years). The full ophthalmologic examination was normal in all eyes before treatment. During the treatment there were no change in visual acuity, refractive error, intraocular pressure and tear break-up time. The mean GCC thicknesses were 81.45?±?4.91, 81.45?±?5.12, 81.81?±?4.68, 81.87?±?4.91 and 81.64?±?5.09?μm at pretreatment and at 1, 3, 6, and 12 months of treatment, respectively (p?=?0.803).

Conclusion: One-year systemic use of isotretinoin had no significant effect on the thickness of macula ganglion cell. Macular ganglion cell analysis is useful for determining and following the toxic effects of systemic drugs on the retina. However, it is more rational to consider it as an adjunct to electrophysiological testing rather than used alone.     

Effect of smoking on retina nerve fiber layer and ganglion cell-inner plexiform layer complex

Purpose: The aim of this study is to show the effects of smoking on retina layers, especially retina nerve fiber layer (RNFL) and ganglion cell-inner plexiform layer complex (GCIPL).

Materials and methods: Participants smoking for more than 10 years at least 1 pack of cigarettes a day and a control group, both including participants between ages of 20 and 50 years with no other systemic or ocular diseases were studied. After normality tests, an independent sample t test was used to analyze the differences in age, sex, spherical equivalent (SE), intraocular pressure (IOP), axial length (AL), GCIPL and RNFL values between the groups.

Results: There were 44 participants in each group. There were 32 (62.5%) men and 12(37.5%) women in smokers and 36 (77.88%) men and 8 (22.22%) women in control group. Mean ages were 39.85?±?8.41 and 38.66?±?10.47 years, mean spherical equivalent (SE) values were ?0.15?±?0.4 and 0?±?0.29 dioptries in smokers and control groups, respectively. The IOP, AXL, GCIPL and RNFL values were 17.58?±?3.41?mmHg, 23.69?±?0.56?mm, 84.3?±?5.83?μm and 92.3?±?3.51?μm in the smokers group and 18.5?±?2.91?mmHg, 23.45?±?0.72?mm, 86.11?±?8.02?μm and 97.66?±?8.23?μm in the control group. The inferior, superior, nasal and temporal values of RNFL quadrants were 123.18?±?26.14, 117.05?±?5.51, 64.95?±?8.67 and 63.5?±?6.88?μm in the smokers group and 130.81?±?11.8, 123.55?±?11.03, 72.44?±?9.84 and 58.44?±?7.48?μm in the control group. There were no significant difference of age, sex, SE, IOP, AXL and GCIPL values between the smokers and control groups (p?>?0.05). The mean RNFL was significantly thinner in the smokers group compared to controls (p?=?0.03, independent t test). Inferior and superior quadrants of RNFL decreased in smokers group (p?=?0.01 and p?=?0.03, respectively) but temporal and nasal quadrants did not seem to be changed (p?=?0.96 and p?=?0.07, respectively).

Discussion: Smoking may affect RNFL thickness but not GCIPL.     

Effect of topiramate on choroidal thickness and anterior chamber parameters in the treatment of patients with migraine

Objective: To investigate the effects of topiramate on choroidal thickness and anterior chamber parameters using optical coherence tomography in the treatment of patients with migraine.

Methods: A total of 22 eyes of 22 adults (12 females, 10 males) diagnosed with migraine and scheduled to topiramate treatment for pain control were recruited in this prospective study. Choroidal thickness (CT), anterior chamber depth (ACD), anterior chamber angle (ACA), spherical refractive equivalent (SphEq) and intraocular pressure (IOP) measurements were recorded at baseline (prior the topiramate therapy), first and second month visits for the statistical analysis. One-way ANOVA with repeated measures test was used for the statistical evaluation.

Results: Mean age of the patients was 40.2?±?6.5?years. Mean CT at central fovea was 324?±?47?μm initially, 341?±?45?μm in the first month and 344?±?46?μm in the second month, thus first and second month measures were significantly higher than base values (p?p?=?0.001). Baseline ACD (3.66?±?0.22?mm) measures significantly decreased at the first month (3.63?±?0.22?mm) and second month (3.62?±?0.22?mm, p?=?0.009). Also, a significant reduction was detected in the first (36.2?±?4.9°) and second month (35.9?±?5.1°) ACA measures comparing with baseline (39.1?±?5.1°, p?=?0.05). A significant myopic shift was determined in the first and second month SphEq values (?0.08?±?0.6, ?0.10?±?0.6, respectively, p?=?0.05).

Conclusions: The study revealed increased CT and altered anterior chamber parameters and IOP due to topiramate therapy. Therefore, the patients using topiramate should be carefully monitored by an ophthalmologist considering the possible side effects.     

Reduced central corneal thickness in patients with isotretinoin treatment

Context: It is well known that oral isotretinoin treatment causes numerous ocular side-effects.

Objective: To investigate the effect of systemic isotretinoin treatment on central corneal thickness (CCT) values due to meibomian gland disease (MGD).

Participants: In this prospective study, 47 patients (27 men, 20 women) with nodulocystic acne vulgaris treated with oral isotretinoin (0.8?mg/kg daily) were included.

Methods: All patients were analyzed with the Pentacam Scheimpflug topography at baseline, on the 3rd and 6th month of treatment. Main outcome measures were MGD scores and CCT.

Results: The mean age of patients was 25.1?±?4.4 years. The mean MGD scores were significantly higher at 3rd month (1.3?±?0.9) and 6th month (1.5?±?1.0) of treatment compared with baseline (1.1?±?0.9) (p?p?p?=?0.038, r?=??0.221).

Conclusion: Isotretinoin treatment causes higher MGD scores. A statistically significant decrease in CCT due to MGD was detected at 6th month of treatment.     

Evaluation of the effects on choroidal thickness of bimatoprost 0.03% versus a brinzolamide 1.0%/timolol maleate 0.5% fixed combination

Objective: To investigate the effects of two different medical treatment options on choroidal thickness (CT) in cases of open-angle glaucoma (OAG).

Methods: Sixty-seven eyes newly diagnosed with OAG and 52 healthy eyes constituting the control group were included in the study. Glaucomatous eyes were randomly divided into two subgroups; Group I was started on bimatoprost 0.03% and Group II on a brinzolamide 1.0%/timolol maleate 0.5% fixed combination (BTFC). Intraocular pressure (IOP), ocular pulse amplitude (OPA) and subfoveal CT measurements were performed in all eyes in the study before treatment and on weeks 2, 4 and 8 after treatment.

Results: Mean initial IOP values in groups I and II and the control group were 25.5?±?4.7, 25.1?±?5.2 and 16.1?±?2.9?mmHg, mean OPA values were 3.7?±?1, 3.6?±?1.4 and 2.4?±?0.6?mmHg and mean CT values were 269.4?±?83, 264.5?±?84.4 and 320.1?±?56.6?μm, respectively. Eight weeks after treatment, mean IOP values in Groups I and II and the control group were 18.3?±?2.6, 18.1?±?3.4 and 15.7?±?2.9?mmHg, mean OPA values were 2.9?±?1.2, 2.8?±?1.5 and 2.3?±?0.8?mmHg and mean CT values were 290.2?±?87.3, 271.8?±?82.5 and 319.3?±?56.8?μm, respectively. No significant difference was determined in terms of the decrease in IOP and OPA obtained after treatment in Group I and Group II. However, a significant difference was observed between the two groups in terms of choroidal thickening after treatment.

Conclusion: The use of topical ocular hypotensive medication in eyes with OAG results in an increase in CT. This increase is relatively greater with bimatoprost 0.03% therapy compared to BTFC.     

Effect of smoking on the thickness of retinal layers in healthy smokers

Purpose: To compare the thicknesses of the retinal layers in smokers with those of nonsmoking healthy subjects using spectral-domain optical coherence tomography (SD-OCT).

Methods: One hundred and eight subjects were included in the study. Two groups were separated as smokers and nonsmokers. Both groups were chosen to be similar in terms of age and gender. SD-OCT images were generated with Spectralis OCT (Heidelberg Engineering, Heidelberg, Germany). An automated algorithm was developed to segment the macular retina into eight layers and quantitate the thickness of each layer for the fovea, parafovea and perifovea.

Results: The mean smoking history was 18.33?±?8.45?years (range: 10–40). The mean number of pack-years was 22.22?±?15.51 (range: 10–80). No significant difference was observed regarding retinal layer measurements between the smoker and nonsmoker groups. Also, no significant difference was observed for central macular thicknesses at 1000, 3000, and 6000?μm between two groups.

Conclusion: The thickness of retinal layers in healthy smokers was similar to those of healthy individuals.     

Change in flash visual evoked potentials in New Zealand albino rabbits after sub-tenon’s anesthesia

Context: The occurrence of amaurosis during ophthalmic anesthesia is well known. The reason for this manifestation has not been studied.

Purpose: To investigate the effect of sub-tenon’s anesthesia on visual conduction in rabbit eyes.

Methods: Fifteen right eyes of 15 New Zealand albino rabbits were included. 2% lidocaine hydrochloride and 0.75% bupivacaine hydrochloride (1?ml, 1:1 mixture) was injected in the sub-tenon’s space of 8 eyes while the control group (n?=?7) was injected with 1?ml physiological saline. Flash visual evoked potentials (FVEP) were performed with Roland reti-scan system before and, 5?min, 15?min, and 5 days after injection. The natural pupillary diameter and minimal pupillary diameter with light reflex were recorded.

Results: In the anesthesia group, N1 latency, P1 latency, and P1 amplitude were 17.13?±?1.13?ms, 28.25?±?1.83?ms, 13.45?±?4.36?μv respectively before injection; 21.75?±?3.06?ms, 29.63?±?2.67?ms, 7.24?±?4.64?μv at 5?min after injection; 22.25?±?1.39?ms, 29.50?±?2.51?ms, 7.54?±?4.47?μv at 15?min after injection, and, 17.75?±?0.71?ms, 28.13?±?2.42?ms, 13.17?±?4.08?μv 5 days after injection. When compared with baseline, N1 latency at 5?min and 15?min after injection showed prolongation (p?=?0.019 and p?=?0.001, respectively). Likewise, P1 amplitude decreased at 5?min and 15?min after injection (p?<?0.001, p?<?0.001, respectively). Both N1 latency and P1 amplitude recovered 5 days after the injection. Pupillary light reflex (PLR) constriction amplitude was 35.42% and 0.00% before and at 5?min after injection (p?=?0.012). After 5 days it recovered to 33.33%. The FVEP and PLR constriction amplitude did not change significantly after injection in the control group.

Discussion: Sub-tenon’s anesthesia was associated with changes in the FVEP and pupullary light reflex in rabbit eyes in our study.

Conclusions: The data from this study suggested that sub-tenon’s anesthesia could reversibly block visual conduction in rabbit’s eyes.     

Efficacy of intravitreal dexamethasone implant for the treatment of macular oedema after pars plana vitrectomy for rhegmatogenous retinal detachment: long-term outcomes

Abstract

Purpose: To investigate the efficacy and safety of intravitreal dexamethasone implant as initial and only treatment for macular oedema after pars plana vitrectomy (PPV) for rhegmatogenous retinal detachment (RRD).

Methods: This study included 14 patients, who were diagnosed with macular oedema after PPV for RRD and who were treated with intravitreal dexamethasone implant. Patients were examined at the time of macular oedema diagnosis (baseline) and 1, 6 and 12?months after treatment, using best corrected visual acuity (BCVA) measurement and optical coherence tomography (OCT).

Results: The mean BCVA at baseline was 0.72?±?0.29 logMAR and improved significantly to 0.37?±?0.21, 0.42?±?0.19 and 0.35?±?0.22 logMAR at month 1, 6 and 12 after treatment with dexamethasone implant. The mean central retinal thickness (CRT) was 623?±?142?μm at baseline and decreased significantly to 339?±?163?μm, 428?±?131?μm and 356?±?147?μm at month 1, 6 and 12 after treatment. Total resolution of macular oedema was observed in 10 out of 14 patients (71.4%) at month 12. Ellipsoid zone was intact in 71.4% of patients at the end of the follow-up, while 71.4% of patients received only one implant until the end of the 12-month follow-up. No adverse events were observed.

Conclusions: Intravitreal dexamethasone implant was found to be effective and safe as initial treatment for macular oedema after PPV for RRD.     

Research on the comparison of the demethylvancomycin’s diffusion–deposition characteristics in the ocular solid tissues of sustained subtenon drug delivery with subconjunctival injection

Purpose: To compare the demethylvancomycin’s diffusion–deposition characteristics in the ocular solid tissues of sustained subtenon drug delivery with subconjunctival injection.

Method: Sixty adult white rabbits were randomly assigned to the subtenon drug delivery group and the subconjunctival injection group. The subtenon drug delivery group was continuously infused demethylvancomycin to the subtenon of rabbits. The subconjunctival injection group was injected demethylvancomycin to the subconjunctival of rabbits. Cornea, iris and sclera were collected for high-performance liquid chromatography analyses to determine drug concentrations at one hour, three hours, six hours, 12?h and 24?h of drug administration. WinNonlin 6.3 was used to calculate the parameters of cumulative area under the curve (AUC_cum) of demethylvancomycin.

Results: The peak levels of demethylvancomycin concentration of the subtenon drug delivery group and the subconjunctival injection group were 92.406?±?21.555 and 51.778?±?14.001?μg/g in cornea, 28.451?±?10.229?μg/g and 42.271?±?27.291?μg/g in iris, 153.166?±?51.738?μg/g and 57.423?±?18.480?μg/g in sclera. The differences of concentrations between the two groups in cornea and sclera were statistically significant (F?=?487.775, p?F?=?132.748, p?F?=?4.848, p?=?0.064). The maximum of AUC_cum of the subtenon drug delivery group and the subconjunctival injection group was 1808.23?h?*?μg/g and 273.73?h?*?μg/g in cornea, 489.12?h?*?μg/g and 216.16?h?*?μg/g in iris and 2166.34?h?*?μg/g and 392.57?h?*?μg/g in sclera at 24?h of drug administration.

Conclusion: The sustained subtenon drug delivery had a better drug permeability and accumulation in the intraocular solid tissue compared to subconjunctival injection, which demonstrated it was probably a promising and effective approach for treating posterior segment diseases and endophthalmitis.     

Phytochemical analysis,antiproliferative and antioxidant activities of Chrozophora tinctoria: a natural dye plant

Context: Chrozophora tinctoria (L.) A. Juss. (Euphorbiaceae) is known as ‘dyer’s-croton’ and used to obtain dye substances. Recently, natural antioxidants and colorants have been of interest because of their safety and therapeutic effects.

Objective: This study investigates the antiproliferative and antioxidant activities of the various extracts and fractions from C. tinctoria and analyzes their phytochemical contents.

Materials and methods: The aerial parts of C. tinctoria were extracted with water, ethyl acetate, n-butanol, and methanol/chloroform. Phenolic compounds and other constituents of the extracts were analyzed by HPLC/TOF-MS. The ethyl acetate extract (EA) was fractionated by flash chromatography. The extracts, fractions, and major phenolic compounds were investigated for their antiproliferative activities on human cervical adenocarcinoma (HeLa) cell line at the concentrations of 5–100?μg/mL by using BrdU ELISA assay during 24?h of incubation. DPPH radical scavenging activities (5–150?μg/mL) and total phenolic contents of the samples were also evaluated.

Results: 4-Hydroxybenzoic acid (268.20?mg/kg), apigenin-7-glucoside (133.34?mg/kg), and gallic acid (68.92?mg/kg) were the major components of EA. CT/E-F6 (IC₅₀?=?64.59?±?0.01?μg/mL) exhibited the highest antiproliferative activity. CT/E-F2 (IC₅₀=?14.0?±?0.0?μg/mL) and some fractions displayed higher radical scavenging activity compared to synthetic antioxidant BHT (IC_50?=_?23.1?±?0.0?μg/mL). Among the main phenolics, gallic acid exhibited the highest antiproliferative and radical scavenging abilities (IC_50?<_?5?μg/mL).

Conclusion: In this study, we have determined the biologically active fractions and their high effects may be attributed to the presence of gallic acid.     

Fabrication and evaluation of lipid nanoparticulates for ocular delivery of a COX-2 inhibitor

Context: The unique physiological limitations of the eye have been assigned as reason of low bioavailability by conventional drug delivery systems. There is need of such drug carriers, which ensure improved bioavailability as well as patient compliance upon instillation into the eye.

Objective: The present investigation deals with development of solid lipid nanoparticles (SLNs) containing celecoxib (CXB) for treatment of ophthalmic inflammations.

Materials and methods: The SLNs were formulated by melt-emulsion sonication and low temperature-solidification process and evaluated for particle size, surface morphology, physicochemical properties, percentage drug incorporation efficiency, in vitro drug release, in vitro trans-corneal permeation, in vivo efficacy in ocular inflammation, stability study and gamma scintigraphy study to assess the residence of solid lipid nanoparticles over ocular surfaces.

Results: The SLNs were spherical and the optimized formulation had particle size of 198.77?±?7.5?nm, which is quite suitable for ocular applications. The maximum entrapment efficiency of 92.46?±?0.07% was achieved for formulation SLN 20. The permeation across the cornea was also significantly better than aqueous suspension (8.21?±?0.67 versus 4.61?±?0.71) at p?<?0.05.

Discussion and conclusion: The SLN formulations demonstrated improved performance of entrapped CXB while mitigating the key parameters of ocular inflammation in rabbits. The particulate formulations have exhibited prolonged retention over ocular surfaces as evident from results of gamma scintigraphy using ^99mTc labeled SLNs.     

Exenatide effects on diabetes,obesity, cardiovascular risk factors and hepatic biomarkers in patients with type 2 diabetes treated for at least 3 years

ABSTRACT

Background: Exenatide, an incretin mimetic for adjunctive treatment of type 2 diabetes (T2DM), reduced hemoglobin A_1c (A1C) and weight in clinical trials. The objective of this study was to evaluate the effects of?≥?3 years exenatide therapy on glycemic control, body weight, cardiometabolic markers, and safety.

Methods: Patients from three placebo-controlled trials and their open-label extensions were enrolled into one open-ended, open-label clinical trial. Patients were randomized to twice daily (BID) placebo, 5?µg exenatide, or 10?µg exenatide for 30 weeks, followed by 5?µg exenatide BID for 4 weeks, then 10?µg exenatide BID for ≥3 years of exenatide exposure. Patients continued metformin and/or sulfonylureas.

Results: 217 patients (64% male, age 58?±?10 years, weight 99?±?18?kg, BMI 34?±?5?kg/m², A1C 8.2?±?1.0% [mean?±?SD]) completed 3 years of exenatide exposure. Reductions in A1C from baseline to week 12 (?1.1?±?0.1% [mean?±?SEM]) were sustained to 3 years (?1.0?±?0.1%; p?<?0.0001), with 46% achieving A1C?≤?7%. Exenatide progressively reduced body weight from baseline (?5.3?±?0.4?kg at 3 years; p?<?0.0001). Patients with elevated serum alanine aminotransferase (ALT) at baseline (n?=?116) had reduced ALT (?10.4?±?1.5?IU/L; p?<?0.0001) and 41% achieved normal ALT. Patients with elevated ALT at baseline tended to lose more weight than patients with normal ALT at baseline (?6.1?±?0.6?kg vs. ?4.4?±?0.5?kg; p?=?0.03), however weight change was minimally correlated with baseline ALT (r?=??0.01) or ALT change (r?=?0.31). Homeostasis Model Assessment B (HOMA-B), blood pressure, and aspartate aminotransferase (AST) all improved. A subset achieved 3.5 years of exenatide exposure and had serum lipids available for analysis (n?=?151). Triglycerides decreased 12% (p?=?0.0003), total cholesterol decreased 5% (p?=?0.0007), LDL-C decreased 6% (p?<?0.0001), and HDL-C increased 24% (p <?0.0001). Exenatide was generally well tolerated. The most frequent adverse event was mild-to-moderate nausea. The main limitation of this study is the open-label, uncontrolled nature of the study design which does not provide a placebo group for comparison.

Conclusion: Adjunctive exenatide treatment for ≥3 years in T2DM patients resulted in sustained improvements in glycemic control, cardiovascular risk factors, and hepatic biomarkers, coupled with progressive weight reduction.     

Saponin-enriched sea cucumber extracts exhibit an antiobesity effect through inhibition of pancreatic lipase activity and upregulation of LXR-β signaling

Context: Sea cucumbers have been consumed as tonic, food, and nutrition supplements for many years.

Objective: The objective of this study is to investigate the antiobesity and lipid-lowering effects of sea cucumber extracts in in vitro and in vivo models and elucidate the mechanism of action of the extracts on obesity and dyslipidemia.

Materials and methods: The 60% ethanol extracts from the body walls of 10 different sea cucumbers were investigated for the inhibition of pancreatic lipase (PL) activity in vitro. The optimal active extract (SC-3) was further chemically analyzed by LC-MS and UV. And 0.1% and 0.2% of SC-3 was mixed with a high-fat diet to treat C57/BL6 mice for 6 weeks or 2 weeks as preventive and therapeutic study. The body weight, serum, and liver lipid profile in the mice were investigated.

Results: The crude extract of Pearsonothuria graeffei Semper (Holothuriidae) inhibited the PL activity by 36.44% of control at 0.5?μg/mL. SC-3 and echinoside A inhibited PL with an IC₅₀ value at 2.86?μg/mL and 0.76?μM. 0.1% of SC-3 reduced the body weight (23.0?±?0.62 versus 26.3?±?0.76 g), the serum TC (2.46?±?0.04 versus 2.83?±?0.12?mmol/L), TG (0.19?±?0.08 versus 0.40?±?0.03?mmo/L), and LDL-c (0.48?±?0.02 versus 0.51?±?0.02?mmol/L), and liver TC (1.19?±?0.17 versus 1.85?±?0.13?mmol/mg) and TG (6.18?±?0.92 versus 10.87?±?0.97?mmol/mg) contents of the obese C57BL/six mice on a high-fat diet.

Discussion and conclusion: Sea cucumber may be used for developing antiobesity and antihyperlipidemia drugs.     

Low concentration of formononetin stimulates the proliferation of nasopharyngeal carcinoma cell line CNE2 by upregulating bcl-2 and p-ERK1/2 expression

Context Formononetin is a typical phytoestrogen, which is a bioactive component found in red clover plants. Previous studies have shown that formononetin inhibits the proliferation of several types of cancer cells, including prostate cancer and osteosarcoma. However, how formononetin affects the proliferation of CNE2 is not clear.

Objective The objective of this study is to investigate the effects of formononetin on nasopharyngeal carcinoma cells in vitro, along with the underlying mechanism.

Materials and methods CNE2 cells were incubated with various concentrations of formononetin (0, 0.1, 0.2, 0.3 and 1?μM) for 48?h. Cell proliferation was measured by [3-(4,5-dimethylthiazol-2-yl)]-2,5-diphenyltetrazolium bromide (MTT) assay, while the rate of apoptosis was measured by flow cytometry. Bcl-2 and bax mRNA expression levels were determined by real time polymerase chain reaction (RT-PCR), while p-ERK1/2 and bcl-2 protein expression levels were quantified by Western blotting.

Results Formononetin promoted the proliferation of CNE2 cells at low concentrations (0, 0.05, 0.1, 0.2, 0.5, 1, 2 and 5?μM), OD values increased from 0.27?±?0.01 to 0.30?±?0.01, 0.30?±?0.01,0.36?±?0.01, 0.35?±?0.01, 0.34?±?0.01, 0.34?±?0.01 and 0.32?±?0.01, respectively. The percentage of late apoptosis declined from 6.77%?±?0.73% (0?μM group) to 6.2%?±?0.4% (0.1?μM group), 3.83%?±?0.71% (0.3?μM group) and 5.1%?±?0.52% (1M group). The mRNA levels of bax and bcl-2 were down- and upregulated, respectively, by formononetin. Bcl-2 and p-ERK1/2 protein levels were also upregulated.

Conclusions Formononetin stimulates CNE2 cell proliferation and has an inhibitory effect on CNE2 cells apoptosis, which is mediated by the activation of the ERK1/2 signaling pathways.     

Bisoprolol/amlodipine combination therapy improves blood pressure control in patients with essential hypertension following monotherapy failure

Objective: The efficacy of a bisoprolol/amlodipine fixed-dose combination (FDC) in patients with essential hypertension who had not responded to bisoprolol or amlodipine monotherapy was investigated.

Research design and methods: In an 18 week, multicenter, randomized, comparative phase III study (ClinicalTrials.gov identifier: NCT01977794), patients with blood pressure uncontrolled by bisoprolol or amlodipine monotherapy (5?mg OD) began treatment with bisoprolol/amlodipine FDC 5/5?mg OD. Patients with controlled blood pressure (BP) at week 6/12 continued at current FDC strength, and patients with uncontrolled BP received FDC dose uptitration (maximum dose: 10/10?mg). The primary efficacy endpoint was change in systolic blood pressure (SBP) at week 18 versus baseline (corresponding to SBP under monotherapy), and secondary endpoints included change from baseline in SBP after week 6/12 and percentage of BP-controlled patients at week 6, 12 and 18. Safety was assessed by number/types of adverse events (AEs).

Results: Two hundred patients were randomized to treatment (100 with uncontrolled BP under bisoprolol and 100 under amlodipine monotherapy). Overall, 196 patients were eligible for analysis. The patient groups displayed similar mean SBP reductions from baseline by study end (bisoprolol monotherapy failure: 25.9?±?12.82?mmHg reduction; amlodipine monotherapy failure: 24.7?±?11.67?mmHg reduction; p?<?0.001 for both). Overall mean SBP decreased by 25.3?±?12.25?mmHg (p?<?0.001). Mean heart rate reductions were also observed (bisoprolol monotherapy failure: 6.6?±?9.67 bpm reduction; amlodipine monotherapy failure: 11.5?±?8.65 bpm reduction; p?<?0.001 for both). Most patients (83.2%) displayed BP control with bisoprolol/amlodipine 5/5?mg at 6 weeks. Treatment was well tolerated at all dose levels; treatment-related AEs (mostly of mild/moderate intensity) were reported by 52.5% of patients, with no severe or serious treatment-related AEs reported. As the study focused on hypertension, total cardiovascular risk was not assessed.

Conclusions: Bisoprolol/amlodipine FDC therapy is associated with significant BP improvements in patients with essential hypertension following monotherapy failure.     

24-Week study on the use of collagen hydrolysate as a dietary supplement in athletes with activity-related joint pain

ABSTRACT

Background: Collagen hydrolysate is a nutritional supplement that has been shown to exert an anabolic effect on cartilage tissue. Its administration appears beneficial in patients with osteoarthritis.

Objective: To investigate the effect of collagen hydrolysate on activity-related joint pain in athletes who are physically active and have no evidence of joint disease.

Design and setting: A prospective, randomized, placebo-controlled, double-blind study was conducted at Penn State University in University Park, Pennsylvania. Parameters including joint pain, mobility, and inflammation were evaluated with the use of a visual analogue scale during a 24-week study phase.

Study participants: Between September 2005 and June 2006, 147 subjects who competed on a varsity team or a club sport were recruited. Data from 97 of 147 subjects could be statistically evaluated.

Intervention: One hundred and forty-seven subjects (72 male, 75 female) were randomly assigned to two groups: a group (n?=?73) receiving 25?mL of a liquid formulation that contained 10?g of collagen hydrolysate (CH-Alpha)^* and a group (n?=?74) receiving a placebo, which consisted of 25?mL of liquid that contained xanthan.

Main outcome measures: The primary efficacy parameter was the change in the visual analogue scales from baseline during the study phase in relation to the parameters referring to pain, mobility, and inflammation.

Results: When data from all subjects (n?=?97) were evaluated, six parameters showed statistically significant changes with the dietary supplement collagen hydrolysate (CH) compared with placebo: joint pain at rest, assessed by the physician (CH vs. placebo (–1.37?±?1.78 vs. –0.90?±?1.74 (?p?=?0.025)) and five parameters assessed by study participants: joint pain when walking (–1.11?±?1.98 vs. –0.46?±?1.63, p?=?0.007), joint pain when standing (–0.97?±?1.92 vs. –0.43?±?1.74, p?=?0.011), joint pain at rest (–0.81?±?1.77 vs. –0.39?±?1.56, p?=?0.039), joint pain when carrying objects (–1.45?±?2.11 vs. –0.83?±?1.71, p?=?0.014) and joint pain when lifting (–1.79?±?2.11 vs. –1.26?±?2.09, p?=?0.018). When a subgroup analysis of subjects with knee arthralgia (n?=?63) was performed, the difference between the effect of collagen hydrolysate vs. placebo was more pronounced. The parameter joint pain at rest, assessed by the physician, had a statistical significance level of p?=?0.001 (–1.67?±?1.89 vs. –0.86?±?1.77), while the other five parameters based on the participants’ assessments were also statistically significant: joint pain when walking (?p?=?0.003 (– 1.38?±?2.12 vs. – 0.54?±?1.65)), joint pain when standing (?p?=?0.015 (–1.17?±?2.06 vs. –0.50?±?1.68)), joint pain at rest with (?p?=?0.021 (–1.01 ±1.92 vs. –0.47?±?1.63)), joint pain when running a straight line (?p?=?0.027 (–1.50?±?1.97 vs. –0.80?±?1.66)) and joint pain when changing direction (?p?=?0.026 (–1.87?±?2.18 vs. –1.20?±?2.10)).

Conclusion: This was the first clinical trial of 24-weeks duration to show improvement of joint pain in athletes who were treated with the dietary supplement collagen hydrolysate. The results of this study have implications for the use of collagen hydrolysate to support joint health and possibly reduce the risk of joint deterioration in a high-risk group. Despite the study's size and limitations, the results suggest that athletes consuming collagen hydrolysate can reduce parameters (such as pain) that have a negative impact on athletic performance. Future studies are needed to support these findings.     

Antioxidant capacity of Typha angustifolia extracts and two active flavonoids

Context: The pollen of Typha angustifolia L. (Typhaceae) has been used as a traditional Chinese medicine for improving the microcirculation and promoting wound healing. Flavonoids are the main constituent in the plant, but little is known about the antioxidant activity of the principal constituent of the pollen in detail.

Objectives: To assess the antioxidant activities of ethanol and water extracts and two constituents of the pollen.

Materials and methods: Plant material (1?g) was extracted by 95% ethanol and water (10?mL?×?2, 1?h each), respectively. The extracted activities (0.8–2.6?mg/mL) were measured by DPPH and the reducing activity of ferric chloride (1.7–2.6?mg/mL). Typhaneoside and isorhamnetin-3-O-neohesperidoside (I3ON) (2.8–70?μmol/L) were investigated on the relationship between NO, MDA and SOD in HUVECs treated with 100?μg/mL of LPS for 24?h.

Results: Nine compounds were identified by UPLC-MS. Ethanol extract showed IC₅₀ values in DPPH (39.51?±?0.72) and Fe³⁺ reducing activity (82.76?±?13.38), higher than the water extract (50.85?±?0.74) and (106.33?±?6.35), respectively. Typhaneoside and I3ON promoted cell proliferation at the respective concentration range of 2.8 to 70?μmol/L (p?p?p?p?Conclusions: The constituents from Typha angustifolia could be a novel therapeutic strategy for LPS-induced inflammation.     

Plasma and tissue disposition of florfenicol in Escherichia coli lipopolysaccharide-induced endotoxaemic sheep

1.?The purpose of this study was to understand the effects of the acute inflammatory response (AIR) induced by Escherichia coli lipopolysaccharide (LPS) on florfenicol (FFC) and FFC-amine (FFC-a) plasma and tissue concentrations.

2.?Ten Suffolk Down sheep, 60.5?±?4.7?kg, were distributed into two experimental groups: group 1 (LPS) treated with three intravenous doses of 1?μg/kg bw of LPS at 24, 16, and 0.75?h (45?min) before FFC treatment; group 2 (Control) was treated with saline solution (SS) in parallel to group 1. An IM dose of 20?mg FFC/kg was administered at 0.75?h after the last injection of LPS or SS. Blood and tissue samples were taken after FFC administration.

3.?The plasma AUC_0–4?h values of FFC were higher (p?=?0.0313) in sheep treated with LPS (21.8?±?2.0?μg·min/mL) compared with the control group (12.8?±?2.3?μg·min/mL). Lipopolysaccharide injections increased FFC concentrations in kidneys, spleen, and brain. Low levels of plasma FFC-a were observed in control sheep (C_max?=?0.14?±?0.01?μg/mL) with a metabolite ratio (MR) of 4.0?±?0.87%. While in the LPS group, C_max increased slightly (0.25?±?0.01?μg/mL), and MR decreased to 2.8?±?0.17%.

4.?The changes observed in the plasma and tissue concentrations of FFC were attributed to the pathophysiological effects of LPS on renal hemodynamics that modified tissue distribution and reduced elimination of the drug.     

Antidiabetic,antilipidemic, and antioxidant activities of Gouania longipetala methanol leaf extract in alloxan-induced diabetic rats

Abstract

Context: Gouania longipetala Hemsl. (Rhamnaceae) is used in folkloric medicine for treating diabetes mellitus and its associated symptoms.

Objective: This study evaluated the antidiabetic antilipidemic and antioxidant activities of the plant methanol leaf extract.

Materials and methods: Diabetes was induced in rats by intraperitoneal injection of alloxan monohydrate (160?mg/kg). Three test doses (50, 100, and 150?mg/kg) of G. longipetala extract (GLE) were administered orally and the effects were compared with glibenclamide (2?mg/kg). The effect of GLE on hyperglycemia and sub-acute study for 21?d were carried out using its effect on fasting blood sugar (FBS) level. Serum biochemistry and antioxidant activity were evaluated. Histopathological evaluation of the pancreas was also done.

Results: The LD₅₀ of G. longipetala was found to be >4000?mg/kg. The extract significantly (p?<?0.0001) decreased the FBS levels of treated rats from 16.2?±?2.03 to 6.5?±?1.52?mM/L at 150?mg/kg within 24?h. The extract decreased FBS levels of rats by 62.0, 74.8, and 75.0% on day 21 at 50, 100, and 150?mg/kg, respectively. GLE reduced the level of malondiadehyde from 23.0?±?1.34?to 10.3?±?0.43?mg/dL, increased superoxide dismutase activities from 2.97?±?0.34 to 5.80?±?0.53?IU/L at 150?mg/kg, and improved the serum lipid profile of treated rats. GLE also caused restoration of the altered histopathological changes of the pancreas.

Discussion and conclusion: Gouania longipetala demonstrated significant antidiabetic, antilipidemic, and antioxidant activities that may be due to its multiple effects involving both pancreatic and extra-pancreatic mechanisms.