Evaluation of the tear film instability in children with allergic diseases

Context: The presence of dry eye syndrome (DES) in ocular allergic diseases was evaluated in several studies. Despite this, little exists about the tear film instability in atopic children including patients with allergic rhinitis (AR), allergic conjunctivitis (AC) and asthma. This is a study which presents intriguing findings regarding the relationship of tear film instability with clinical aspects in atopic children.

Objective: To determine the tear film instability in children with AR, AC and asthma.

Materials and methods: One hundred and thirty-five consecutive children with AR, AC and asthma as study group and 45 children without any systemic and ocular abnormality as control group were included in the study. Skin prick tests, measurement of tear film breakup time (TFBUT), serum immunoglobulin E and eosinophil counts were performed in all patients. Also four subgroups of patients were designated as AR group (Group I), AC group (Group II), asthma group (Group III) and control group (Group IV).

Results: Socio-demographic characteristics were similar except for family atopy between the groups (p?>?0.05). The mean TFBUT was significantly lower in the study group (15.5?±?4.4?s) than the control group (18.4?±?2.9?s; p?=?0.000). Also, there was no significant differences in the percentage of the patients who has TFBUT<10?s (p?=?0.066). In logistic regression analysis, atopy was found to be the determinant of lower TFBUT (OR?=?16.33, 95%; CI?=?1.17 to 228.05, p?=?0.03).

Conclusion: The presence of tear film instability was higher in children with AC, AR and asthma. This finding should be taken in consideration in atopic children.     

Long term effect of sulfur mustard exposure on hematologic and respiratory status,a case control study

The long term effect of sulfur mustard (SM) exposure including, total and differential white blood cells (WBC), hematological parameters, pulmonary function tests (PFT), and respiratory symptoms (RS) in chemical war victims (CWV) exposed to SM 27–30 years ago were examined. Forty-six CWV and 42 control subjects with similar age from the general population were studied. Hematologic parameters, RS including; chest wheezing, night cough, night wheezing and cough, wheezing due to exercise (by Persian questionnaire), and PFT were assessed in all subjects. Total WBC count (p?<?0.001), hematocrit, and mean corpuscular volume (MCV) were significantly higher (p?<?0.05 and 0.001, respectively) but mean corpuscular hemoglobin concentration (MCHC) and the percent of monocyte were lower in veterans than control group (p?<?0.001 and 0.01, respectively). All PFT values were also lower in CWV compared to control subjects (p?<?0.001 for all cases). Maximal mid expiratory flow (MMEF) and maximal expiratory flow at 75% of forced vital capacity (MEF75) were the most affected PFT values in CWV and were 50% or lower of predicted values. All CWV reported respiratory symptoms, including; chest wheezing, night cough, night wheezing and cough, and wheezing due to exercise were higher in the veterans compared to control group (p?<?0.001 for all cases). Increased total WBC count and RS but reduction in monocyte, MCHC, and PFT values were shown in CWV 27–30 years after exposure to SM. These results indicated profound hematologic (mainly WBC) and pulmonary effect of SM long time after exposure.     

Possible involvement of nitric oxide in antidepressant-like effect of silymarin in male mice

Abstract

Context: Silymarin (SM) is extracted from milk thistle Silybum marianum L. [Asteraceae (Compositae)] and known for antioxidative and anti-inflammatory effects.

Objective: The potential antidepressant-like effect of acute SM and possible involvement of nitric oxide (NO) were determined in male mice.

Material and methods: SM was administered orally (5, 10, 20, 50, 100, and 200?mg/kg; p.o.) 60?min before the tests. After assessment of locomotor activity, the immobility time was measured in forced swimming test (FST) and tail suspension test (TST). To assess the possible involvement of NO, a non-specific NO synthase inhibitor, l-NAME (10?mg/kg, i.p.), and a specific iNOS inhibitor, aminoguanidine (AG) (50?mg/kg, i.p.), were administered separately 30?min before SM (20 and 100?mg/kg).

Results: SM at its effective doses 10, 20, 50, and 100?mg/kg decreased the immobility time in a dose-dependent manner (p?<?0.01, p?<?0.05, p?<?0.05, and p?<?0.001, respectively) in FST. SM (10, 20, 50, and 100?mg/kg) also lowered the immobility measure dose dependently in TST (p?<?0.01, p?<?0.05, p?<?0.01, and p?<?0.001, respectively). In addition, 50% of maximum response (ED₅₀) of SM was around 10?mg/kg. The dose 100?mg/kg proved the most effective dose in both the tests. Further, this effect was not related to changes in locomotor activity. Moreover, l-NAME reversed the effect of SM (20 and 100?mg/kg) in FST and SM (100?mg/kg) in TST. However, AG did not influence this impact.

Conclusion: The antidepressant-like effect of SM is probably mediated at least in part through NO and SM may increase NO tune.     

Specific IgE for wheat in tear fluid of patients with allergic conjunctivitis

Context: Allergy to hydrolyzed wheat protein in facial soap has become a major social issue in Japan. It has been reported that the most frequent early symptoms of allergy to hydrolyzed wheat protein in soap are allergic conjunctivitis and rhinitis, while wheat-dependent exercise-induced anaphylaxis can be induced by long-term use.

Objective: We evaluated the relation between tear fluid levels of specific IgE for wheat and the features of allergic conjunctivitis.

Methods: A prospective, non-randomized, cross-sectional study was conducted in 103 patients with moderate to severe allergic conjunctivitis (allergic group) and 20 age- and sex-matched healthy control subjects (control group). Specific IgE for wheat was measured in tear fluid with an immunochromatography assay, and a skin prick test (SPT) was also performed. Symptoms (sneezing, rhinorrhea, nasal obstruction, ocular itching, and lacrimation) were assessed in each subject along with the activities of daily living (ADL) score and the total ocular symptom score for allergic conjunctivitis. A severity score (0, 1, 2, or 3) was assigned for various changes of the palpebral and bulbar conjunctiva, as well as for limbal and corneal lesions associated with allergic conjunctivitis.

Results: The IgE positive rate and specific IgE score were both higher in the allergic group than in the control group (71.8% versus 40.0% and 1.9?±?0.7 versus 1.4?±?0.5). A positive SPT for wheat was also more frequent in the allergic group than in the control group (6.8% versus 0.0%). Within the allergic group, patients with a positive SPT had higher specific IgE scores than patients with a negative SPT (3.3?±?0.5 versus 1.8?±?0.6, p?r?=?0.665), tearing (r?=?0.672), and the total ocular symptom score (r?=?0.204). Wheat IgE in tear fluid was also correlated with the severity of rhinitis symptoms, including sneezing (r?=?0.610), nose blowing (r?=?0.640), and nasal obstruction (r?=?0.677). Furthermore, the tear fluid wheat IgE score was correlated with five objective features of allergic conjunctivitis (p?Conclusions: These results suggest that wheat allergy may be involved in the development of allergic conjunctivitis.     

Tolerability of loteprednol/tobramycin versus dexamethasone/tobramycin in healthy volunteers: results of a 4-week,randomized, double-masked,parallel-group study

ABSTRACT

Objective: To compare the ocular comfort and tolerability of loteprednol etabonate 0.5%/tobramycin 0.3% (LE/T; Zylet^*) with dexamethasone 0.1%/tobramycin 0.3% (DM/T; TobraDex^?) in healthy volunteers.

Research design and methods: In this multicenter, randomized, double-masked, parallel-group study, healthy volunteers (n?=?306) were randomized to receive LE/T or DM/T four times per day for 28 days. Subjects recorded subjective ratings for seven comfort/tolerability parameters using an electronic patient diary (EPD). The primary endpoint was the difference at week 4 from the ratings of an artificial tear at baseline in comfort/tolerability parameters between treatment groups, using a noninferiority paradigm.

Clinical trials registration: ClinicalTrials.gov, NCT 00532961.

Results: The 97.5% confidence intervals for the lower bound were within –10 for all of the seven comfort/tolerability parameters evaluated (pain, stinging/burning, irritation, itchiness, foreign-body sensation, dryness, and light sensitivity). Secondary analysis revealed small but significant within-treatment differences in pain favoring LE/T over tears and in light sensitivity favoring tears over DM/T (p?<?0.01). Small between-treatment differences in the changes from baseline tear ratings to individual study visits favored LE/T for pain, stinging/burning, irritation, itchiness, foreign-body sensation, and light sensitivity at visit 4 (p?≤?0.04); for pain, stinging/burning, and foreign-body sensation at visit 5 (p?≤?0.03), and for dryness and light sensitivity at visit 6 (p?≤?0.05).

Conclusions: LE/T satisfied all conditions of noninferi-ority to DM/T in comfort and tolerability. Subjects receiving LE/T were more likely to report better ocular comfort/tolerability ratings relative to baseline artificial tears than subjects receiving DM/T.

Limitations: The study population consisted of healthy volunteers.     

The effect of sulfur mustard and nitrogen mustard on corneal collagen degradation induced by the enzyme collagenase

Objective: Sulfur mustard (SM) is an alkylating agent that can affect cornea and induce various complications. With regard to the role of the enzyme collagenase in dermatologic complications induced by SM and its role in other ocular disorders, we studied the effect of SM and nitrogen mustard (NM) on collagen degradation by collagenase.

Materials and methods: This study included 7 groups of samples: The negative control group contained collagen without collagenase and toxins, the control group contained collagen and collagenase without any toxin, the positive control groups of NM and SM contained collagen and NM or SM without collagenase, the experimental groups of NM and SM contained collagen that was affected by NM or SM and collagenase, and the control group of collagenase contained only collagenase without containing collagen or receiving toxins. After incubation for 3.5 hours, the amount of hydroxyproline and the protein content of the samples were measured. Data were analyzed by analysis of variance (ANOVA).

Results: The protein concentrations of the negative control group and the positive control groups of SM and NM were significantly lower than those for all other groups of the study. There was a significant difference in hydroxyproline concentration of control group and negative control group; however, there was no significant difference between experimental group of SM and the positive conrol group of SM. There was no significant difference between the negative control group and the positive control group of SM in the hydroxyproline concentration of sediment samples.

Conclusion: According to the results of this study, SM can affect the corneal collagen in a way in which collagenase cannot degrade it. In addition, it can be hypothesized that ineffective activity of this enzyme can result in increasing concentration of collagenase, which can lead to the destruction of the normal collagen of the cornea. The main result of this study confirms the hypothesis that SM inhibits the effect of collagenase on corneal collagen.     

Antidepressant-like effects of magnesium lithospermate B in a rat model of chronic unpredictable stress

Abstract

Context: Magnesium lithospermate B (MLB), an active polyphenol acid of Danshen [Radix Salviae miltiorrhizae (Labiatae)], shows neuroprotective and anti-inflammatory effects in vivo and in vitro.

Objective: We hypothesized that MLB might exert antidepressant-like effects by targeting the neuroinflammatory signals.

Materials and methods: Sprague-Dawley rats were subjected to the chronic unpredictable stress (CUS) protocol. Rats in the control group received no CUS during the whole experiment. In the model group, rats were exposed to CUS for 7 weeks. From the beginning of the 5th week, model group rats were randomly grouped and subjected to different treatments. In the experiment, control and model group rats were intraperitoneally (i.p.) injected with saline. MLB was dissolved in saline to give a final concentration, and the rats were injected (i.p.) with 15, 30, or 60?mg/kg MLB once a day for 3 weeks.

Results: MLB administration significantly reduced: (1) the immobility time in the forced swimming test (19?s, p?<?0.05); (2) the immobility time in the tail suspension test (76.3?s, p?<?0.05); (3) the corticosterone (CORT) concentrations in the serum (21.7?nmol/L, p?>?0.05); (4) the pro-inflammatory cytokine levels in the serum – TNF-α (92.1?pg/ml, p?<?0.05), IL-1β (86.9?pg/ml, p?<?0.05), and IL-6 (93.8?pg/ml, p?<?0.05); (5) pro-inflammatory cytokine levels in tissue – TNF-α (3.2?pg/mg protein, p?<?0.05), IL-1β (1.5?pg/mg protein, p?>?0.05), and IL-6 (6.3?pg/mg protein, p?<?0.05); and (6) phospho-NF-κB (1.6, p?<?0.05) and phospho-IκB-α (0.4, p?<?0.05) expression in tissue.

Discussion and conclusion: The results suggested that MLB might exert therapeutic actions on depression-like behavior and the HPA axis hyperactivity in CUS rats, and the mechanisms underlying the antidepressant-like effects of MLB might be mediated by regulation of the expression of NF-κB and IκB-α in rats.     

Effect of bisphenol A on blood glucose,lipid profile and oxidative stress indices in adult male mice

Abstract

Bisphenol A (BPA), an endocrine-disrupting chemical, has been considered as a possible risk factor for diabetes and its complications. However, the underlying mechanisms of BPA-induced diabetes are not clear. The present study was performed to evaluate the effects of BPA on the hyperglycemia, lipid abnormalities and oxidative stress. In this study, the mice were divided into three groups of six animals each: One group as a control (C) and two other groups which exposed to 0.5 and 2?mg/kg concentrations of BPA. BPA powder was dissolved in sterile extra virgin olive oil and injected intraperitoneally to the tested groups, while the control group only received pure olive oil for 4 weeks. After 4 weeks, the changes of glucose, lipid profile reduced, total protein, glutathione (GSH), malondialdehyde (MDA), total antioxidant status (TAS), catalase (CAT) and super oxide dismutase (SOD) were determined in serum and pancreas. The results indicated that BPA dose-dependently increased the levels of blood glucose, lipid profile and MDA in the tested groups compared with the control group (p?<?0.001). BPA reduced significantly the levels of HDL-C and GSH in dose-dependent manner (p?<?0.001). BPA injection increased the levels of MDA and decreased the levels of GSH and TAS, and also the activities of SOD and CAT in the pancreas of exposed mice compared with the control group (p?<?0.05). In addition, body weight increased in the mice exposed to BPA compare to control animals. These results suggest that BPA exposure might induce hyperglycemia and its complications in adult male mice by induction of oxidative stress.     

Effects of Labrasol on the corneal drug delivery of baicalin

Purpose: To investigate the use of Labrasol in ocular drug delivery system.

Methods: The in vivo ocular irritation of Labrasol was tested by pathological section observation using rabbits. The effects of Labrasol on corneal permeability of baicalin was investigated in vitro, using isolated rabbit corneas. The pharmacokinetics was evaluated by microdialysis in the rabbit aqueous humors.

Results: The results of the ocular irritation studies showed that Labrasol was non-irritant at the concentrations studied (0.5–3.0%(v/v)), while Labrasol produced slight irritation at a concentration of 5.0%(v/v). For the in vitro study, with Labrasol at concentrations of 1.5%, 2.0%, and 3.0%(v/v), the apparent permeability coefficient (P_app) was 1.69-, 3.14-, and 2.23- fold of baicalin solution, respectively. In the pharmacokinetics studies, the AUC value of baicalin solution with 2.0% and 3.0%(v/v) Labrasol were 4.7- and 5.6-fold of that of the control group (p?<?0.01), and the C_max value of baicalin solution with 2.0% and 3.0%(v/v) Labrasol vs the control group were 3.2- and 5.7-fold (p?<?0.01).

Conclusion: Labrasol may have potential clinical benefits in improving the ocular drug delivery of baicalin.     

Metformin pretreatment enhanced learning and memory in cerebral forebrain ischaemia: the role of the AMPK/BDNF/P70SK signalling pathway

Context Metformin induced AMP-activated protein kinase (AMPK) and protected neurons in cerebral ischaemia.

Objective This study examined pretreatment with metformin and activation of AMPK in molecular and behavioral levels associated with memory.

Materials and methods Rats were pretreated with metformin (200?mg/kg) for 2 weeks and 4-vessels occlusion global cerebral ischaemia was induced. Three days after ischaemia, memory improvement was done by passive avoidance task and neurological scores were evaluated. The amount of Brain-Derived Neurotropic Factor (BDNF) and phosphorylated and total P70S6 kinase (P70S6K) were measured.

Results Pretreatment with metformin (met) in the met?+?ischaemia/reperfusion (I/R) group reduced latency time for enter to dark chamber compared with the sham group (p?<?0.001) and increased latency time compared with the I/R group (p?<?0.001). Injection of Compound C (CC) (as an AMPK inhibitor) concomitant with metformin reduced latency time in I/R rats compared with the I/R?+?met group (p?<?0.05). Neurological scores were reduced in met treated rats compared with the sham group. Pretreatment with metformin in I/R animals reduced levels of pro-BDNF compared with the I/R group (p?<?0.001) but increased that compared with the sham group (p?<?0.001). The level of pro-BDNF decreased in the met?+?CC?+?I/R group compared with the met?+?I/R group (p?<?0.01). Pretreatment with metformin in I/R animals significantly increased P70S6K compared with the I/R group (p?<?0.001).

Conclusion Short-term memory in ischaemic rats treated with metformin increased step-through latency; sensory-motor evaluation was applied and a group of ischaemia rats that were pretreated with metformin showed high levels of BDNF, P70S6K that seemed to be due to increasing AMPK.     

Efficacy of Aloe vera/olive oil cream versus betamethasone cream for chronic skin lesions following sulfur mustard exposure: a randomized double-blind clinical trial

Background: Chronic pruritic skin lesions are among the common late complications of sulfur mustard intoxication. In the present randomized double-blind clinical trial, therapeutic efficacy of Aloe vera/olive oil combination cream in the alleviation of these lesions was evaluated and compared to that of betamethasone 0.1% cream.

Methods: Sixty-seven Iranian chemical warfare-injured veterans were randomized to apply A. vera/olive oil (n?=?34, completers?=?31) or betamethasone 0.1% (n?=?33, completers?=?32) cream twice daily for 6 weeks. Evaluation of pruritus severity was performed using a pruritic score questionnaire and visual analogue scale (VAS).

Results: Both treatments were associated with significant reductions in the frequency of pruritus (p?<?0.05), burning sensation (p?<?0.01 and p?<?0.001 in A. vera/olive oil and betamethasone group, respectively), scaling (p?<?0.01 and p?<?0.05) and dry skin (p?<?0.001) at the end of trial. Fissure and excoriation were only reduced in the A. vera group (p?<?0.05). The change in the frequency of hyper- and hypopigmentation lesions, blisters, erythema and lichenification did not reach statistical significance in any of the groups (p?>?0.05). Mean pruritus (p?<?0.05) and VAS scores (p?<?0.01 and p?<?0.05) were significantly decreased by the end of trial in both groups. The rate of improvement in the pruritus severity [defined as being classified in a less severe category (mild, moderate and severe)] was found to be comparable between the groups (p?>?0.05).

Conclusion: A. vera/olive oil cream was at least as effective as betamethasone 0.1% in the treatment of sulfur mustard-induced chronic skin complications and might serve as a promising therapeutic option for the alleviation of symptoms in mustard gas-exposed patients.     

Ocular findings in coal miners diagnosed with pneumoconiosis

Objective: Our study aimed at evaluating ocular findings and structural changes in coal mine workers who were chronically exposed to coal mine dust and diagnosed with pneumoconiosis.

Methods: Ocular findings of 161 eyes of 81 patients diagnosed with pneumoconiosis who had previously worked or are currently working in coal mines were analyzed. Forty-six coal mine workers and sex matched healthy people (n?=?20) participated in the study. Workers who had early changes of pneumoconiosis were included in Group 1 (n?=?17), workers diagnosed with pneumoconiosis were included in Group 2 (n?=?29), and healthy subjects were included in Group 3 (n?=?20). Outcome measures were the difference in peripapillary retinal nerve fiber layer (RNFL) thickness, choroidal thickness (CT), central macular thickness (CMT) and tear function tests between the groups.

Results: RNFL thickness values in Group 1 and 2 were lower than in Group 3, the control group, in all quadrants except the temporal quadrant. However, there was no statistically significant difference in peripapillary RNFL thickness values in any quadrants among the three groups (p?>?0.05). Central subfoveal choroidal thickness and CMT measurements were thinner in Group 1 and 2 than in the control group. However, this difference among groups was not statistically significant (p?>?0.05). Mean schirmer's test result was 8.8?±?1.6?mm in group 1, 7.1?±?1.8?mm in Group 2 and 11.5?±?3.6?mm in the control group. Mean tear break up time (BUT) test result was 7.1?±?1.3?seconds (sec) in Group 1, 6.5?±?1.8?sec in Group 2 and 10.4?±?2.9?s in the control group. The Schirmer's test and BUT test results were both statistically significantly lower in coal mine workers (Group 1 and 2) compared to the control group. Group 1 and Group 2 did not show statistically significant difference in terms of Schirmer's test and BUT test results.

Discussion: The association between pneumoconiosis and coal mine dust contiguity is thought to be due to the effect of coal dust by producing chronic inflammation. In addition, there are several trace elements in coal dust which are toxic to vital tissues. In this study, ocular findings suggest that systemic levels of trace elements and chronic inflammation may not reach to a level that influences ocular structures. Nonetheless, tear functions seem to be affected in coal mine workers.

Conclusion: This study suggests that the systemic effect of coal mine dust in ocular structures is not evident. However, direct contact with coal mine and fume leads to a decrease in tear function tests.     

Thermosensitive in situ nanogel as ophthalmic delivery system of curcumin: development,characterization, in vitro permeation and in vivo pharmacokinetic studies

Context: The nanogel combining cationic nanostructured lipid carriers (CNLC) and thermosensitive gelling agent could enhance preocular retention and ocular permeation capacity of curcumin (CUR).

Objective: The purpose of the study was to develop and characterize a thermosensitive ophthalmic in situ nanogel of CUR-CNLC (CUR-CNLC-GEL) and evaluate in vitro and in vivo properties of the formulations.

Materials and methods: The physicochemical properties, in vitro release and corneal permeation, were evaluated. Ocular irritation and preocular retention capacity were also conducted. Finally, pharmacokinetic study in the aqueous humor was investigated by microdialysis technique.

Results: The solution–gel transition temperature of the optimized formulation diluted by simulated tear fluid was 34?±?1.0?°C. The CUR-CNLC-GEL displayed zero-order release kinetics. The apparent permeability coefficient (P_app) and the area under the curve (AUC_0→∞) of CUR-CNLC-GEL were 1.56-fold and 9.24-fold, respectively, than those of curcumin solution (CUR-SOL, p?<?0.01). The maximal concentration (C_max) was significantly improved (p?<?0.01). The prolonged mean residence time (p?<?0.01) indicated that CUR-CNLC-GEL is a controlled release formulation.

Discussion and conclusion: Those results demonstrated that CUR-CNLC-GEL could become a potential formulation for increasing the bioavailability of CUR in the aqueous humor by enhancing corneal permeation and retention capacity.     

Evaluation of an isotonic tear in combination with topical cyclosporine for the treatment of ocular surface disease

ABSTRACT

Purpose: To determine whether a new category of artificial tear product, carboxymethylcellulose 0.5% with compatible solutes (CMC-solutes) (Optive, Allergan, Inc., Irvine, California) improves clinical outcomes when used adjunctively with topical cyclosporine 0.05% (Restasis, Allergan, Inc., Irvine, California) for the treatment of ocular surface disease.

Methods: Nineteen patients with ocular surface disease treated with cyclosporine 0.05% for at least 3 months and who had previously used other artificial tears adjunctively were enrolled. Patients discontinued their previous artificial tear and used CMC-solutes, concomitant with topical cyclosporine 0.05%. Corneal evaluation and tear production parameters were evaluated before and during combined CMC-solutes/cyclosporine treatment. Patients also completed a questionnaire before and during treatment with combined CMC-solutes/cyclosporine. Follow-up was at 1 and 3 months.

Results: Most objective measures of ocular surface health were unchanged, but an improvement in conjunctival lissamine green staining and tear break-up time was found. Conjunctival lissamine green staining scores improved from 3.4 ± 2.5 to 1.9 ± 2.5 by Month 3 (?p = 0.004). Tear break-up time improved from 4.6 ± 3.9?s pre-treatment to 5.3 ± 3.8?s post-treatment (?p = 0.049). Ocular Surface Disease Index (OSDI) scores improved from 16.2 ± 9.4 at baseline to 11.5 ± 8.9 at month 3 (?p = 0.007). Subjectively, patients graded their ocular discomfort as 2.7 at baseline and as 2.3 at Month 3 (?p = 0.049). At Month 3, 89.5% of patients said they liked CMC-solutes as well or better than previous drops they had used. All patients said CMC-solutes provided similar or improved relief of symptoms of dry eye than previous eye drops. There were no tear-related adverse events reported.

Conclusions: In this study, CMC-solutes, when used in conjunction with cyclosporine 0.05%, provided patients with an improvement in objective signs and subjective symptoms of ocular surface disease compared to their previous artificial tears. Further studies are warranted.     

Effect of mulberry leaf (Folium Mori) on insulin resistance via IRS-1/PI3K/Glut-4 signalling pathway in type 2 diabetes mellitus rats

Context: Folium Mori, the leaf of Morus alba L. (Moraceae), has been used in traditional Chinese medicine (TCM) for treating diabetes. However, it is unclear which components in the mulberry leaf are effective for the treatment of type 2 diabetes mellitus (T2DM).

Objective: To investigate the flavonoids and polyphenols in mulberry leaves and their antihyperglycemic and antihyperlipidemic effects in T2DM rats.

Materials and methods: Male Sprague-Dawley rats were divided into five groups: normal control (NC), diabetic control (DBC), diabetic group with 0.3?mg/kg b.w./day rosiglitazone (RSG), diabetic group with 7?g/kg b.w./day TCM formula and diabetic group with 2?g/kg b.w./day Folium Mori extract (FME). After 4 weeks, the rats were sacrificed; biochemical parameters, gene and protein expression were measured.

Results: The FBG level was significantly lower in the FME group than in the DBC group (p?<?0.05). In oral glucose tolerance test, the AUC was significantly lower in the FME group (p?<?0.05). The HOMA-IR level was significantly decreased in the FME group (p?<?0.05). FME decreased the total cholesterol (TC), triglyceride (TG) and low density lipoprotein (LDL) levels (p?<?0.05). FME increased the mRNA and protein expression of IRS-1, PI3K p85α and Glut-4 increased significantly (p?<?0.05). Histological analysis revealed amelioration of lipid accumulation following FME treatment. Additionally, immunohistochemical analysis displayed stronger staining of Glut-4 in the FME group compared to the DBC group.

Discussion and conclusion: FME could decrease the body weight, blood glucose, TG, TC and LDL levels, and improve insulin resistance. FME possessed significant antihyperglycemic and antihyperlipidemic activities via the IRS-1/PI3K/Glut-4 signalling pathway.     

Placenta structural changes in heavy smoking mothers: a stereological aspect

Objective: Smoking during pregnancy is able to alter the structure and function of the placenta. In the present study, quantitative changes of the placenta in smoking mothers were investigated compared to healthy controls by Cavalieri’s point counting method.

Methods: Twenty placentas from heavy smoking mothers and non-smoker controls (n?=?10 in each group) were selected. Systematic uniform random sampling (SURS) was used for sample selection and tissue sectioning. Quantitative parameters of the placenta in the selected sections were estimated after Masson’s trichrome staining. Differences between the two groups were determined by the Mann Whitney U test and the significance level was set at p?<?.05.

Results: Results showed that there was a significant difference in the placental weight, total volume of placenta, intervillous space, fibrin and syncytiotrophoblast between the heavy smoker group and the control group (p?<?.05). The differences in the volume density of fibrin and blood vessels between the smoker and control groups were statistically significant (p?<?.05).

Conclusions: Our findings suggested that quantitative parameters of the placenta significantly changed in placentas from the smoker group compared to controls. These changes can probably be associated with pregnancy complications in smoking mothers and may affect the development and survival of the fetus and even its future life.     

Wound healing potential of naringin ointment formulation via regulating the expression of inflammatory,apoptotic and growth mediators in experimental rats

Context: Wound healing is a consequence of a complex process involving inflammatory, proliferative, and remodeling phases. Naringin, a flavanone glycoside, is associated with modulation of various oxido-inflammatory and growth factors.

Aim: The aim of this study is to evaluate the wound-healing activity of naringin ointment formulation (NOF) on experimental wound models.

Materials and methods: A soft paraffin-based cream containing 1, 2, and 4% (w/w) naringin was formulated and evaluated for physicochemical characters. Excision wounds and incisions wounds were used to study the topical effect of NOF for 20 d (once a day) on various biochemical, molecular, and histological parameters.

Results: NOF (2 and 4%, w/w) treatment showed a significant decrease (p?<?0.05) in wound area and epithelization period whereas the rate of wound contraction increased significantly (p?<?0.05). The altered levels of oxido-nitrosative stress (SOD, GSH, MDA, MPO, and NO) were significantly (p?<?0.05) restored by NOF. Treatment produced a significant increase (p?<?0.05) in tensile strength, hydroxyproline content, and protein content. TNF-α, IL-1β, IL-6, IL-8, NF-κB, smad-7, and Bax mRNA expression were significantly down-regulated (p?<?0.05) by NOF, whereas polymerase gamma (pol-γ), smad-3, VEGF and TGF-β, and collagen-1 mRNA expressions were significantly up-regulated (p?<?0.05) by NOF. Histological alterations in wound skin were also restored by NOF.

Conclusion: NOF exerts wound healing potential via down-regulated expression of inflammatory (NF-κB, TNF-α, and ILs), apoptotic (pol-γ and Bax), and up-regulated growth factor (VEGF and TGF-β) expression, thus modulating collagen-1 expression to induce angiogenesis leading to wound healing.     

Biological activities of salvianolic acid B from Salvia miltiorrhiza on type 2 diabetes induced by high-fat diet and streptozotocin

Abstract

Context: Salvia miltiorrhiza Bge. (Labiatae) has been widely used for treating diabetes for centuries. Salvianolic acid B (SalB) is the main bioactive component in Salvia miltiorrhiza; however, its antidiabetic activity and possible mechanism are not yet clear.

Objective: To investigate the effects of SalB on glycometabolism, lipid metabolism, insulin resistance, oxidative stress, and glycogen synthesis in type 2 diabetic rat model.

Materials and methods: High-fat diet (HFD) and streptozotocin-induced diabetic rats were randomly divided into model group, SalB subgroups (50, 100, and 200?mg/kg), and rosiglitazone group.

Results: Compared with the model group, SalB (100 and 200?mg/kg) significantly decreased blood glucose (by 23.8 and 21.7%; p?<?0.05 and p?<?0.01) and insulin (by 31.3 and 26.6%; p?<?0.05), and increased insulin sensitivity index (by 10.9 and 9.3%; p?<?0.05). They also significantly decreased total cholesterol (by 24.9 and 27.9%; p?<?0.01), low-density lipoprotein cholesterol (by 56.2 and 64.6%; p?<?0.01), non-esterified fatty acids (by 32.1 and 37.9%; p?<?0.01), hepatic glycogen (by 41.3 and 60.5%; p?<?0.01), and muscle glycogen (by 33.2 and 38.6%; p?<?0.05), and increased high-density lipoprotein cholesterol (by 50.0 and 61.4%; p?<?0.05 and p?<?0.01), which were originally altered by HFD and streptozotocin. In addition, SalB (200?mg/kg) markedly decreased triglyceride and malondialdehyde (by 31.5 and 29.0%; p?<?0.05 and p?<?0.01), and increased superoxide dismutase (by 56.6%; p?<?0.01), which were originally altered by HFD and streptozotocin.

Discussion and conclusion: The results indicate that SalB can inhibit symptoms of diabetes mellitus in rats and these effects may partially be correlated with its insulin sensitivity, glycogen synthesis and antioxidant activities.     

Ocular surface findings in patients with rheumatoid arthritis under methotrexate or biological agent therapy

Purpose: To evaluate the ocular findings in patients with rheumatoid arthritis (RA) treated with disease-modifying antirheumatic drugs (DMARDs) such as methotrexate (MTX) or MTX with biological agents.

Methods: One hundred and twelve eyes of 56 patients with RA and treated with MTX or MTX with biological agents were included in the study. Patients were divided into two groups using DMARDs only (group 1) and patients using DMARDs and biologic agents together (group 2). In both groups; Schirmer’s II test, tear film break-up time (tBUT), central corneal thickness (CCT), corneal volume (CV), intraocular pressure (IOP) measurement, and anterior segment and fundus examinations of the eye with slit lamp were carried out. Ocular surface disease index (OSDI) score questionnaire were performed.

Results: Thirty-eight patients with a mean age of 53.00?±?8.19 years were in group 1 and 18 patients with a mean age of 51.00?±?9.54 years were in group 2. The mean duration of RA was 6.89?±?7.96 years in group 1 and 5.70?±?9.00 years in group 2. There was a statistically significant difference between two groups with tBUT, CCT, CV, IOP (p < 0.05) and there was no significant difference with age, sex, disease duration, disease activity, and Schirmer’s II test (p > 0.05). The disease duration showed a significant moderate negative correlation with CCT and CV in group 2 (p < 0.05).

Conclusions: Although tBUT values were significantly higher in the combination treatment group, CCT and CV values were significantly lower. Due to the decrease in corneal thickness, IOP was determined to be significantly lower.     

Effect of alpha lipoic acid on smoking-induced skin damage

Objective: Exposed to cigarette leads to the formation of reactive oxygen species and the generation of bioactive molecules that can damage skin cells. This investigation was carried out to study possible effects of Alpha Lipoic Acid (ALA) on smoking-induced rat skin injury.

Materials and methods: 28 Spraque–Dawley female rats were allocated into three groups: control group (n?=?8), smoking group (n?=?10; 12 cigarettes/day, 8 weeks) and smoking?+?ALA group (n?=?10; 12 cigarettes/day?+?100?mg/kg, 8 weeks). Experiment group animals were sacrificed under anaesthesia with 10%ketamine?+?2%xylasine at the end of second mounts and then skin examples were taken from the epigastric area. Histochemical (Haematoxylin–Eosin and Masson’s trichrome, immunohistochemical (TNF-α) and biochemical analysis (CAT, MDA and protein carbonylation) were performed on these skin tissues.

Results: Histologically, skin was distinguished normal structure in the control group. In the smoking group, collagen bundles and hair follicle degradation/reduction, sweat gland degeneration, mononuclear cell infiltration in dermis were encountered. In ALA-treated group, all of these changes were improved (p?<?0.05). Collagen bundles structures were appearance more regular than the smoking group . Immunohistologically, intense staining was observed in the smoking group, while very weak staining was observed in control group, weak staining was observed in the ALA-treated group. Biochemically; The CAT activity compared to cigarette group with control was raised high and in ALA group was higher compared to both groups, but not significant (p?>?0.05). MDA; which is indicator of lipid peroxidation was significantly higher in cigarette group than in control group (p?<?0.05) and was significantly lower in ALA group than cigarette (p?<?0.05). Protein carbonylation was higher in cigarette group than the control group but not in the non-significant (p?>?0.05). In the ALA it was significantly lower compared to the control group and cigarette (p?<?0.05).

Conclusions: Based on biochemical and histopathological determinations, the study showed that cigarette smoke can cause degenerative effects on skin tissues in rats. However, ALA has a curative effect on cigarette-induced injuries on the skin tissues by anti-oxidative and anti-inflammatory effects.