Impact of vaginal douching products on vaginal Lactobacillus, Escherichia coli and epithelial immune responses

We compared the effect of commercial vaginal douching products on Lactobacillus crispatus, L. jensenii, L. gasseri, L. iners, E. coli, and immortalized vaginal epithelial cells (VK2). All studied douching products (vinegar, iodine and baking soda based) induced epithelial cell death, and all inhibited growth of E. coli. Co-culture of vaginal epithelial cells with any of the lactobacilli immediately following exposure to douching products resulted in a trend to less human cell death. However, co-culture of epithelial cells with L. iners was associated with higher production of IL6 and IL8, and lower IL1RA regardless of presence or type of douching solution. Co-culture with L. crispatus or L. jensenii decreased IL6 production in the absence of douches, but increased IL6 production after exposure to vinegar. Douching products may be associated with epithelial disruption and inflammation, and may reduce the anti-inflammatory effects of beneficial lactobacilli.

Dyspareunia, Signs of Epithelial Disruption, and HIV Serostatus in Female Sex Workers and Men Who Have Sex With Men in Nairobi: an Observational Study

Background: This study investigated HIV infection risk in men who have sex with men (MSM) and female sex workers (FSWs) by analysing signs of anal and vaginal epithelial trauma. It reconsidered the unique role of sexual abstinence for HIV seroconversion from a previous case-control analysis on FSWs in Nairobi who acquired HIV after previously fulfilling criteria of HIV resistance. The approach was based on a similarly unique role of intercourse frequency for anal dyspareunia. We considered confounding behavioural and individual HIV infection risks among the sex workers, who also assessed factors influencing discomfort and pain during sex from a subjective perspective. Methods: At two key population facilities in Nairobi, 322 FSWs and 231 MSM provided data on HIV infection status, sexual dysfunction, intercourse frequency and abstinence behaviour. Additional data addressed sexual debut, relationship status, lubricants, foreplay, the number of sex partners, condom use, group and anonymous sex, vaginal births, intravaginal practices, sex toys, other sexually transmitted infections, alcohol and drug use. Statistical tests included t-tests for the equality of means for abstinence gaps and intercourse frequencies, the number of sex partners, vaginal births, and age of sexual debut. Non-parametric tests were used to compare HIV status and the ordinal variables of sexual behaviour, individual factors, dyspareunia and signs of trauma scores. Subjective assessments of variables for sexual dysfunction were given as percentages of the assessment options. Results: Among FSWs, significant associations were found between HIV status and the longest abstinence gap for vaginal intercourse in the previous month, early sexual debut, foreplay, having anonymous partners, intravaginal practices, drugs and alcohol use, and all the sexual dysfunction or epithelial disruption signs. No significant association between HIV status and sexual dysfunction variables or sexual abstinence gaps could be found in the MSM sample. FSWs agreed that steady partnerships, regularity of intercourse, foreplay and lubrication or artificial lubricants alleviate discomfort and painful intercourse. Conclusions: Dyspareunia and epithelial trauma signs were highly prevalent in FSWs and MSM, indicating considerable limitations to sexual health. Complaint levels were positively associated with HIV infection, suggesting that reducing epithelial disruption may be a novel HIV prevention approach.

Matriptase activation of Gq drives epithelial disruption and inflammation via RSK and DUOX

Epithelial tissues are primed to respond to insults by activating epithelial cell motility and rapid inflammation. Such responses are also elicited upon overexpression of the membrane bound protease, Matriptase, or mutation of its inhibitor, Hai1. Unrestricted Matriptase activity also predisposes to carcinoma. How Matriptase leads to these cellular outcomes is unknown. We demonstrate that zebrafish hai1a mutants show increased H2O2, NfkB signalling, and IP3R -mediated calcium flashes, and that these promote inflammation, but do not generate epithelial cell motility. In contrast, inhibition of the Gq subunit in hai1a mutants rescues both the inflammation and epithelial phenotypes, with the latter recapitulated by the DAG analogue, PMA. We demonstrate that hai1a has elevated MAPK pathway activity, inhibition of which rescues the epidermal defects. Finally, we identify RSK kinases as MAPK targets disrupting adherens junctions in hai1a mutants. Our work maps novel signalling cascades mediating the potent effects of Matriptase on epithelia, with implications for tissue damage response and carcinoma progression.

Breaching the Delivery Barrier: Chemical and Physical Airway Epithelium Disruption Strategies for Enhancing Lentiviral-Mediated Gene Therapy

The lungs have evolved complex physical, biological and immunological defences to prevent foreign material from entering the airway epithelial cells. These mechanisms can also affect both viral and non-viral gene transfer agents, and significantly diminish the effectiveness of airway gene-addition therapies. One strategy to overcome the physical barrier properties of the airway is to transiently disturb the integrity of the epithelium prior to delivery of the gene transfer vector. In this study, chemical (lysophosphatidylcholine, LPC) and physical epithelium disruption using wire abrasion were compared for their ability to improve airway-based lentiviral (LV) vector mediated transduction and reporter gene expression in rats. When luciferase expression was assessed at 1-week post LV delivery, LPC airway conditioning significantly enhanced gene expression levels in rat lungs, while a long-term assessment in a separate cohort of rats at 12 months revealed that LPC conditioning did not improve gene expression longevity. In rats receiving physical perturbation to the trachea prior to gene delivery, significantly higher LacZ gene expression levels were found when compared to LPC-conditioned or LV-only control rats when evaluated 1-week post gene transfer. This proof-of-principle study has shown that airway epithelial disruption strategies based on physical perturbation substantially enhanced LV-mediated airway gene transfer in the trachea.

Essential Oils Derived from Momordica charantia Seeds Exhibited Antiulcer Activity against Hydrogen Chloride/Ethanol and Indomethacin

Momordica charantia (MC) is popular for its medicinal uses especially for treating diabetic-related complications. However, the antiulcer activity of essential oil derived from the seeds has not been systematically studied. This study aims to evaluate the gastroprotective activities of essential oil derived from the seed of MC induced by hydrochloride acid/ethanol (HCl/EtOH) and indomethacin and pylorus-ligation model. Gastric ulceration was induced by oral administration of HCl/EtOH solution or indomethacin on day 7 after animals have been pretreated with testing compounds. The first group received just distilled water and the second group received ranitidine (100 mg/kg). Groups 3, 4, and 5 received 10, 50, and 100 mg/kg of essential oil based on their body weight (10 mL/kg), respectively. Macroscopically, pretreatment of essential oil extracted from MC significantly decreased ulceration induced by HCl/EtOH and indomethacin in vivo. Microscopically, essential oil also significantly suppressed the formation of edema, epithelial disruption, and mucosa erosions. Moreover, essential oil significantly elevated the pH without decreasing the total acidity of the gastric juice and was able to increase the amount of adherent mucus compared to control. Current results provide scientific basis to the ethno-pharmacological usage of the MC in preventing ulcer formation induced by HCl/EtOH and indomethacin.

Effects of Sodium Chloride-Rich Mineral Water on Intestinal Epithelium. Experimental Study

Since knowledge concerning the cellular and tissue substrate that explains the therapeutic action of mineral waters is generally very scarce, we address the different effects that Lanjarón-Capuchina mineral water exerts on the intestinal epithelium in an experimental model as a prototype of the sodium chloride-rich mineral waters used in digestive disorders. In the experimental protocol, two groups of five adult Wistar rats received unrestricted mineral water in their diet or mineral water directly into the gastrointestinal tract through a catheter. A third control group was given a standard diet and water ad libitum. Intestinal samples for scanning electron microscopy were analyzed according to standardized methods. The observations carried out by microscope after the administration of the sodium chloride-rich mineral water clearly indicate that the hypertonic action of this mineral water affects the structure of the intestinal epithelium. It modifies the microvilli absorption in terms of the groups of enterocytes and the secretion of goblet cells, but it particularly affects the epithelial renewal process, accelerating and stimulating cell extrusion. The type of extrusion mechanism observed by microscope allows us to affirm that, although this increased after direct administration, it does not generate an epithelial disruption as it occurs in other circumstances with other extrusion modalities.

Choroidal neovascularisation following inverted internal limiting membrane flap technique for idiopathic macular hole: a case for modified flaps

A 70-year-old woman presented with sudden decrease of vision 2 months following a successful vitrectomy with inverted internal limiting membrane flap for a full thickness macular hole. Serial review of fundus pictures and optical coherence tomography scans revealed a focal retinal pigment epithelial disruption at the site of the macular hole after surgery and a choroidal neovascular membrane arising from the same. This report describes the possible role of the surgical technique in causation of the membrane and discusses modifications to avoid the same.

Mangiferin Alleviates Ovalbumin-Induced Allergic Rhinitis via Nrf2/HO-1/NF-κB Signaling Pathways

Mangiferin (MF), extracted from mango trees, is considered to have anti-inflammatory, anti-apoptotic, and antioxidant effects. However, its effects on allergic rhinitis (AR), remain unclear. We investigated the mechanisms underlying the protective action of MF in ovalbumin (OVA)-induced AR models. AR was induced by OVA challenge in BALB/c mice. Prior to this, MF and dexamethasone were administered. Mice were examined for nasal mucosal inflammation, the generation of allergen-specific cytokine response, and histopathological changes in the nasal mucosa and lung tissue. MF ameliorated nasal symptoms and nasal mucosa inflammation in OVA-induced AR and reduced inflammatory cell infiltration and epithelial disruption in these tissues. MF inhibited the overproduction of Th2/Th17 cytokines and transcription factors. MF downregulated the HO-1/Nrf2 pathways, reduced oxidative stress biomarker levels, and the NF-κB signaling pathways were inhibited. MF exerts protective effects in AR by inhibiting NF-κB and activating HO-1/Nrf2 pathways. MF could be used for the treatment of AR.

D-trans-allethrins in Some Selected Mosquito Coil Repellents Causes Histological Inflammation in Trachea of Experimental Animals

Background: Many reports on the toxicity of some mosquito repellents have been recorded, however, its effect on the trachea. Aim: This study was aimed at determining the Histopathological and Morphological changes in Trachea of Wistar rats exposed to selected mosquito repellents commonly used in Sokoto, Nigeria especially after the recent outbreak of Malaria and Dengue fever. Methods: Mosquito repellent brands of Pyrethroids-containing mosquito coil, aerosolized spray and Dichlovors aerosolized spray were studied over 21 days. Rats were exposed to the fumes in coils and aerosolized insecticidal spray for 5 minutes each day, in a well-ventilated box. Control rats were not exposed. Animals were sacrificed on days 7, 14 and 21 post-exposure. Results: Early observable behavioural signs include irritation, scratching of the eyes and nostrils; in later stages of exposure, sneezing, ruffled fur and lethargy were observed. Gross changes were not apparent in most organs, except for frothy trachea observed in few Wistar rats exposed to the fumes. Histopathology revealed varying degrees of epithelial disruption, lymphocytic infiltration and vascular congestion; more apparent 7 days post-exposure and to a lesser degree, 21 days post-exposure. The severity of the macroscopic changes was more in the first 14 days of exposure while it was reduced in rats that were exposed for 21 days. The most obvious changes were observed in coil repellents containing Rich-d-Trans allethrin. Conclusion: Acute exposure to fumes of mosquito repellents containing rich-d-trans allethrin is irritating to the trachea and could lead to possible respiratory problems.

Fourier Analysis of Keratometric Data in Epithelium Removal versus Epithelial Disruption Corneal Cross-linking

Purpose: To compare epithelium-removal and epithelium-disruption corneal crosslinking (CXL) methods in Fourier analysis of keratometric data and clinical outcomes. Methods: In this double-masked randomized clinical trial, each eye of 34 patients with bilateral keratoconus was randomly allocated to either the epithelium-removal or epithelium-disruption CXL treatment groups. Ocular examination, refraction, uncorrected and best spectacle-corrected visual acuity (UCVA and BSCVA, respectively) measurements, and Pentacam imaging (keratometry, pachymetry, and Fourier analysis) were performed at baseline and at six-month follow-up period. Results: Patients’ mean age was 23.3 ± 3.6 years. The preoperative thickness of the thinnest point was 459.20 ± 37.40 μm and 455.80 ± 32.70 μm in the epithelium removal and epithelial-disruption CXL groups, respectively (P = ?). The corresponding figures were 433.50 ± 33.50 μm and 451.90 ± 39.70 μm, respectively, six months after the treatment (P = 0.0001). The irregularity component was 0.030 ± 0.016 μm in the epithelium-removal group and 0.028 ± 0.011 μm in the epithelium-disruption group preoperatively (P = ?). This measurement was 0.031 ± 0.016 μm and 0.024 ± 0.009 μm, respectively at month 6 (P = 0.04). The epithelium-disruption CXL group had better results in terms of the thickness of the thinnest point and the irregularity component as compared to the epithelium-removal group. The two study groups were comparable in spherical equivalent, mean keratometry, UCVA, BSCVA, or other Fourier analysis components (spherical R min, spherical eccentricity, central, peripheral regular astigmatism, and maximum decentration) (P > 0.05). Conclusion: This study shows that epithelium-disruption CXL is superior to epithelium removal CXL regarding the short-term changes in pachymetry and corneal irregularity. Other evaluated parameters were comparable between the two techniques within the six-month follow-up period.