Metabolomic Analysis of Skin Malodor-Associated Compounds and Structure-based Prediction of Acetolactate Synthase Selective Sulfonylurea Inhibitors

Bromhidrosis is characterized as a chronic condition related to malodor from the skin. The underlying etiology is from bacterial decompositions of glandular secretion products. However, specific pathways and metabolites for the disease are yet to be investigated. Here, twenty-eight metabolites, including fifteen major sweat constituents and thirteen compounds emitted from malodor-producing skin bacteria, were subjected to the metabometric analysis using Metaboanalyst. Different pathways in the butanoate metabolism revealed that acetolactate synthase (ALS) in skin Staphylococcus epidermidis (S. epidermidis) bacteria are catalyzing pyruvate to several malodor compounds like diacetyl. In the docking studies of the sulfonylurea-ALS interaction, five selected sulfonylureas, which originally were developed for the treatment of diabetes mellitus type 2, showed different binding free energies (ΔG) from chlorimuron ethyl - a well-known ALS sulfonylurea inhibitor. Amongst five sulfonylureas, gliquidone and glisoxepide were found to have free energy differences that were lower than or equal to chlorimuron ethyl, revealing their high affinities to ALS. In the future, further investigations of gliquidone and glisoxepide against ALS in skin bacteria would be crucial in repurposing these two sulfonylureas as new anti-bromhidrosis drugs.

Impact of the Glycemic Level on the Salivary Proteome of Middle-Aged and Elderly People With Type 2 Diabetes Mellitus: An Observational Study

Type 2 diabetes mellitus (T2DM) is an increasing global public health concern, but its impact on the salivary proteome is still unclear. To evaluate the effect of glycemic levels in middle-aged and elderly individuals with T2DM on salivary proteomics, we compared the differences by liquid chromatography tandem mass spectrometry (LC–MS/MS). Unstimulated whole saliva samples from 8 T2DM patients with good glycemic control (G group, HbA1c <6.5%) and 16 patients with poor control (P group, HbA1c ≥6.5%) were analyzed by LC–MS/MS in the data-independent acquisition mode (Clinical register number: ChiCTR1900023582.). After functional annotation, cluster analysis and receiver operating characteristic (ROC) curve analysis were carried out to screen and evaluate candidate proteins. A total of 5,721 proteins were quantified, while 40 proteins differed significantly. In the P group, proteins involved in oxidative stress-related processes were upregulated, whereas proteins related to salivary secretion were downregulated. The combination of thioredoxin domain-containing protein 17, zymogen granule protein 16B, and FAM3 metabolism regulating signaling molecule D yielded an area under the curve of 0.917 which showed a robust ability to distinguish the P and G groups. In conclusion, poorly controlled hyperglycemia may affect salivary proteins through various pathways, including oxidative stress and glandular secretion. Furthermore, the differentially expressed proteins, especially the three proteins with the best differentiation, might serve as an anchor point for the further study of hyperglycemia and oral diseases.

Correlation of Chronic Smoking with Meibomian Gland Dysfunction – A Study at Wardha, Maharashtra, India

BACKGROUND Meibomian gland dysfunction (MGD) is one of the causes of evaporative dry eye disease. It is the terminal duct obstruction of the Meibomian gland and is associated with glandular secretion changes. These changes lead to decreased amount of lipids secretion which accounts for instability of tear film leading to evaporative dry eye disease. Chronic smoking also causes irritative, burning eyes along with unstable tear film. We wanted to study the corelation of chronic smoking with Meibomian gland dysfunction. METHODS This is a hospital based observational cross-sectional study that enrolled a total of 100 subjects having Meibomian gland disease (MGD), out of whom 61 were smokers and 39 were non-smokers. All enrolled subjects underwent tear film breakup time (TBUT), Schirmer I test (SIT) and slit-lamp microscope examination of lid margin abnormalities, Meibomian gland expression as well as meibum. RESULTS Our study found that the patients with Meibomian gland dysfunction with the history of chronic smoking had a remarkably decreased value of tear film break up time (TBUT), Schirmer’s 1 Test which explains the dry eye symptoms as compared to MGD patients without smoking. No significant differences were seen in lid margin irregularity and meibum secretion. Meibomitis is found in 29 smokers with MGD and 5 non-smokers with MGD which is not significant. CONCLUSIONS Chronic smoking is associated with MGD. KEY WORDS Cigarette Smoking, Meibomian Gland Dysfunction, Tear Film Tests

Social Immunity in Honey Bees: Royal Jelly as a Vehicle in Transferring Bacterial Pathogen Fragments Between Nestmates

Social immunity is a suite of behavioral and physiological traits that allow colony members to protect one another from pathogens and includes the oral transfer of immunological compounds between nestmates. In honey bees, royal jelly is a glandular secretion produced by a subset of workers that is fed to the queen and young larvae, and which contains many antimicrobial compounds. A related form of social immunity, transgenerational immune priming (TGIP), allows queens to transfer pathogen fragments into their developing eggs where they are recognized by the embryo's immune system and induce higher pathogen-resistance in the new offspring. These pathogen fragments are transported by vitellogenin (Vg), an egg-yolk precursor protein that is also used by nurses to synthesize royal jelly. Therefore, royal jelly may serve as a vehicle to transport pathogen fragments from workers to other nestmates. To investigate this, we recently showed that ingested bacteria are transported to nurses’ jelly-producing glands, and here, we show that pathogen fragments are incorporated into the royal jelly. Moreover, we show that consuming pathogen cells induces higher levels an antimicrobial peptide found in royal jelly, defensin-1.

Histology, lectin histochemistry and ultrastructure of interdigital gland in crossbred sheep

Histology, lectin histochemistry and ultrastructure of interdigital gland in sheep was studied using six adult cross bred sheep of either sex collected from the Meat Technology Unit, College of Veterinary and Animal Sciences, Mannuthy. The manus and pes were detached from the rest of limbs and after recording the gross observations, the interdigital glands were fixed in 10 per cent neutral buffered formalin and processed for histological examinations. Stratified squamous epithelium with a prominent keratin layer lined the lumen, similar to the skin over the dorsal surface of manus and pes. The epidermis presented mucosal folds, which projected into the lumen. The dermis contained small sebaceous glands, hair follicles of different sizes, arrector pili muscles and apocrine sweat glands. The secretory epithelium of sweat glands was lined with a simple layer of cuboidal and relatively flattened cells. The excretory ducts of these glands were lined by cuboidal cells, with darker appearance than its secretory portion. The fibrous capsule was composed of dense connective tissue with collagen, adipose cells, blood vessels and nerve fibers. Glandular secretion and the granules in the stratum granolosum of the surface squamous epithelium showed positive reaction for lectin Ulex europaeus (UEA-I). The apocrine nature of sweat glands was revealed in the ultrastructural studies by scanning electron microscope. Keywords: Interdigital gland, sheep, histology, lectin histochemistry and ultrastructure

Penehyclidine mitigates intraoperative oculocardiac reflex and postoperative nausea and vomiting in the patients with strabismus surgery: a prospective, randomized, double-blinded comparison

BackgroundPONV is one of the most frequent complications following anesthesia and strabismus surgery. Penehyclidine, an anticholinergic, is widely and preoperatively used for reducing glandular secretion in patients. This study investigated the effect of penehyclidine on PONV in strabismus surgery.MethodsIn this prospective, randomized, and double-blinded study, patients of strabismus surgery under general anesthesia were randomly assigned to either penehyclidine (n = 114) or normal saline (NS, n = 104) groups. Penehyclidine was administrated immediately after anesthesia induction, and patients treated with NS served as controls. PONV was investigated within 48 h after surgery. Intraoperative OCR was also recorded.ResultsCompared with NS controls, penehyclidine significantly reduced PONV incidence [30.7% vs. 54.8%, P < 0.001] and mitigated PONV severity as indicated by severity scoring (P < 0.001). When stratified by gender and age, the reduction of PONV incidence following penehyclidine treatment was found significant in all adult patients and male underaged patients. Unexpectedly, penehyclidine also significantly reduced OCR incidence [57.9% vs. 77.9%, P < 0.01] and mitigated OCR severity which indicated by requirement of atropine to rescue [77.3% vs. 90.1%, P < 0.05]. Moreover, penehyclidine did not significantly change anesthesia recovery time, facial flushing and drowsiness occurrence compared to NS controls.ConclusionsPenehyclidine administration after anesthesia induction significantly attenuated intraoperative OCR and PONV in strabismus surgery patients.Trial registrationClinicalTrials.gov (NCT04054479). Registered July 19, 2019, https://www.clinicaltrials.gov/ct2/show/NCT04054479?id=NCT04054479&draw=2&rank=1

Characterization of Meibomian Gland Dysfunction in Patients with Rosacea

Background: Rosacea frequently evolve the eyes with impact on life and vision quality. There are gaps in the understanding of ocular involvement, specially related to eyelid glands, which share common features to sebaceous glands.Purpose: Describe ocular surface disease related to Rosacea and its associations.Methods: Ninety-three individuals were selected to this cross-sectional, observational, non-interventionist study, divided into groups: rosacea (n=40) and controls (n=53). We investigated objective parameters of the ocular surface (conjunctival hyperemia, tear film stability and volume, meibomian gland dysfunction, dry eye disease, ocular surface staining) comparing healthy individuals with rosacea patients.Results: 69.23% of rosacea group were women, mean age of 47.34 ± 12.62 years old. Compared to matched controls there was no statistically significant differences regarding to visual acuity (p=0.987) and tear film parameters (tear meniscus height (p=0.338), non-invasive tear film rupture time (NIBUT) (p= 0.228), invasive rupture time (TBUT) (p=0.471) and Schirmer's test (p=0.244)) as well as conjunctival hyperemia (p = 0.106), and fluorescein staining (p = 0.489). Significant association was found in meibography evaluation (p = 0.026), mucous layer integrity (p = 0.015) and ocular surface symptoms (p <0.0001). Rosacea patients also showed important eyelid changes: glandular expressibility (p <0.001), glandular secretion pattern (p <0.001) and telangiectasia (p <0.001) compared to controls.Conclusion: Meibomian gland dysfunction is frequently associated to dermatologic conditions and is characterized by morphological findings in the meibography as well as lipid secretion impairment that lead to evaporative dry eye and ocular surface dysfunction and inflammation.

Pharmacological safety of using medicinal drugs in patients with dry eye syndrome and in patients with the risk of dry eye syndrome development

The dry eye syndrome (DES) belongs to the group of tear film disorders, which are caused by either lowering of tear secretion or by the tear film instability. DES lowers the working capacity, worsens the quality of life and, if its symptoms are ignored for a long time, may lead to serious vision disorders, including blindness. The influence of environmental factors may be one of the reasons for intensification of the DES caused symptoms. In addition, there is a concept of iatrogenic DES, caused by a systemic and local use of medicinal drugs, by contact lenses, and by ophthalmological surgical and non-surgical manipulations. The purpose of the research was to study the clinical-pharmacological characteristics of medicinal drugs in terms of peculiarities of their application in patients with DES who have adjoining disorders as well as to determine medicines that may contribute to DES occurrence and exacerbation causing secondary lowering of tear production and sensor glandular secretion, inflammation of Meibomian glands or direct irritation. Materials of the research included the data of the medicinal drugs’ register, the search database of medicinal drugs Compendium, prescribing information and labelling of the drugs. Methods of research: biblio-semantic, content-analysis, segmenting, graphic, system analysis. It has been determined that 194 medicinal drugs, which in accordance to the 1st level of ATC-classification system belong to 10 pharmaco-therapeutic groups, have certain treatment peculiarities in patients with dry eye syndrome. DES is mentioned in different sections of prescribing information and labelling of the drugs: «side effects» – 172 drugs, «peculiarities of use» – 21 drug, «drug-to-drug interaction» – 1 drug. Segmentation of the market by the type of medicinal form demonstrated a significant prevalence of eye drops and pills (34.02% and 33.50% respectively). Taking into consideration the prevailing share of eye drops among other medicinal forms, which cause iatrogenic DES, further research is required to study their composition and define the correlation between the content of excipients and the risk of development of side effects in the form of dry keratoconjunctivitis of local ophthalmological medicinal drugs. The results of the conducted complex research determine the groups of medicinal drugs that should be prescribed with special caution for pharmacotherapy of various organs and systems in patients with the risk of DES acquisition or exacerbation. The most numerous among them are such groups as S01E – Antiglaucoma drugs and myotics, L01X – Antineoplastic drugs and N02B – Analgesics and antipyretics, which account for 21.13%, 12.37% and 9.79%, respectively. Presence of information about the risk of DES development as a result of drug-to-drug interaction in only 1 of 194 prescribing information and labelling of the drugs signifies an extremely low level of attention to the issue of medicinal drugs’ synergy in terms of their side effects.

Ethno-veterinary practices of Poaceae taxa in Punjab, Pakistan

Background: Plant species of Poaceae family are not only used as fodder and forage but also contribute substantially in the treatment of various health disorders, particularly in livestock. Consequently, present study was aimed to document the therapeutic uses Poaceae taxa by the inhabitants of the Punjab Province to treat various veterinary health disorders. Methods: Semi structured interviews, group discussion and field walks were conducted to collected data. Furthermore, quantitative indices includingcultural significance index (CSI), relative frequency of citations (RFC), fidelity level (FL), and relative popularity level (RPL) andJaccard Index (JI) were adopted for data analysis. Results: Traditional uses of 149 plants belonging to 60 genera, 16 tribes of 5 sub families of Poaceae were recorded. Whole plant and leaves were the most consistent grazing parts with 40.94 and 29.53% contribution and decoction (35 reports) was the most preferred mode of administration. Majority of the plant species were employed to treat infectious diseases (25.93 %). and digestive disorders (14.10 %). Triticum aestivum depicted highest CSI, RFC and RPL levels at 8.00, 0.96, 1.00, respectively, followed by Oryza sativa and Poa annua . Likewise, T. aestivum and Saccharum spontaneum had 100 % FL and ROP. Jaccard index ranged from 12.25 to 0.37. Twelve plant species namely Chrysopogon zizanioides (anti-inflammatory), Pennisetum lansatum (improve bull fertility), Cymbopogon citratus (glandular secretion), Sorghum saccharatum and Themeda triandra (malaria), Aristida funiculate (anticancer) , Koeleria argentia (skin allergies), Tetrapogon villosus (antibacterial), Cynodon radiates (eyes infection), Sporobolus nervosa (Jaundice), Enneapogon persicus (antifungal), and Panicum repens (dysfunctional cattle organs) were reported for the first time with novelethnoveterinary uses. Conclusion: Inhabitants of the study area had strong association with surrounding plant biodiversity and possess significant knowledge on therapeutic uses of grasses and other members of Poaceae to treat various health disorders in animals. Plant species with maximum cultural and medicinal values could be a potential source of novel drugs to cure health disorders in animals and human as well.