Why does my joint hurt: Understanding disease phenotype and pain relationships using mouse models of arthritis

Osteoarthritis (OA), characterised by progressive joint-wide pathology, is a major health problem accounting for 48% of people living with chronic pain. There are no treatments to slow OA progression and symptom managing therapies are at best moderately effective. This failure results from a poor understanding of the mechanisms that drive OA pain. Animal models are widely used to study OA pain molecular pathways, but pre-clinical findings fail to translate into effective therapeutics for patients. In part this may be because animal models have poorly defined phenotypes not mapped to specific sub-types of human OA. This research aimed to define the relationship between joint tissue pathology, pain behaviour and gene expression in the dorsal root ganglia (DRG), over time comparing models of post-traumatic OA (DMM) and inflammatory arthritis (AIA), and identify differences in what drives pain. DMM and AIA ultimately displayed similar hallmark histopathology of OA in late stage disease. However, each model had distinct temporal patterns of pathology; associations between articular cartilage, synovium and bone pathology; and risk factors for progression. Both models displayed sensitisation (tactile allodynia, mechanical and thermal hyperalgesia) and altered gait (reduced hindlimb weight bearing, changes in stride length). However, the severity and temporal pattern of occurrence were model-specific. At each phase of OA development, DRG gene expression changes were also model-specific. It was predominantly synovium and bone pathology that were significantly associated with altered DRG gene expression and pain behavior, but differentially in the two models. The DRG expression changes associated with altered pain behaviours were also model-specific. Combined these findings demonstrate that DMM and AIA are phenotypically unique models of OA, defined not only by initiating cause, but temporal pattern and inter-dependence of joint pathology, pain characteristics, and molecular drivers. The results suggest that the mechanisms regulating joint pain are specific to the disease pathophysiology, and confirm the importance of mapping pre-clinical findings to specific human disease phenotypes. This challenges the current way animal models are used to investigate OA pain mechanisms and test therapeutics

Does the use of supraglottic device in rabbits cause less injury than other airway management devices?

PICO question In rabbits, undergoing general anaesthesia, does the placement of a v-gel® device result in less airway trauma compared to the use of other airway management devices?   Clinical bottom line Category of research question Treatment The number and type of study designs reviewed Three papers were critically appraised, two blinded randomised experimental trial studies and one randomised crossover experimental trial study Strength of evidence Weak Outcomes reported One blinded randomised trial study demonstrated that the trauma to the upper airways of rabbits during anaesthesia is not significantly different between the use of v-gel® and an endotracheal tube. The other blinded randomised trial study demonstrated that the trauma to the upper airway caused by endotracheal intubation is significantly more than that caused by v-gel® placement. The randomised crossover trial study demonstrated that v-gel® placement causes more significant compression to the larynx compared to a laryngeal mask or face mask Conclusion The current evidence suggests that use of the v-gel® in rabbits causes less trauma / injury to the airways compared to placement of an endotracheal tube but not compared to the use of a laryngeal or face mask. However, based on the low number and quality of published studies, this evidence is weak, and better-quality studies are required to support the routine use of v-gel® over other airway devices in rabbits. While v-gel® may be a safer alternative for securing airways in rabbits compared to endotracheal intubation, knowing the injuries this device can cause to the upper airways is useful for managing rabbits during post anaesthesia recovery   How to apply this evidence in practice The application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. Knowledge Summaries are a resource to help reinforce or inform decision making. They do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care

Anticandidal Activity of Green Synthesized Zinc Oxide Nanoparticles Using Lemon Peel Extract

Nanobiotechnology has developed as an effective technology for developing antimicrobial nanoparticles in an environmentally safe manner. In this study, green synthesized zinc oxide nanoparticles (ZnO NPS) from zinc acetate solution by using lemon peels aqueous extract was characterized by UV–Visible Spectroscopy, High-resolution Transmission Electron Microscopy (HR-TEM) and Dynamic Light Scattering (DLS). Anticandidal activity was investigated against three clinical multidrug resistant Candida species including two Candida albicans, one Candida glabrata and one Candida krusei using four antifungal agents by disc diffusion method and antifungal activity of ZnO NPS was assayed by disc diffusion method and determination of the minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC). Characterization studies revealed that the synthesized nanoparticles have rod shape with sizes of 13.58 - 30.70 nm. Notably, high rates of resistance were observed with the four tested antifungal agents against all Candida species and the antifungal activity of the synthesized ZnO NPS against Candida species were exhibited, with a maximum zone of inhibition of 24.5±0.5 mm against C. glabrata followed by C. albicans (19.5±0.5 mm) and C. krusei (16.0±0.0 mm). MIC and MFC for all Candida species were 0.25 and 0.5 mg/ml respectively. The cytotoxic data indicates that ZnO NPs have half maximal inhibitory concentration (IC50) value = 230.12 ± 9.34 μg/ml on normal human lung fibroblast cell line (MRC5). In conclusion, the study elucidates that lemon peels mediated green synthesized zinc oxide nanoparticles have antifungal activity against different Candida species. So that it can be developed as a novel medicine for the treatment of Candida associated infections in the near future

Evaluation of the Native Killer Yeasts against the Postharvest Phytopathogenic mould of Balady Orange Fruits

Yeasts are some of the most important postharvest biocontrol agents (BCAs). Postharvest oranges frequently deteriorate due to green and blue moulds, leading to significant economic losses. The purposes of the present study were to isolate blue and green moulds from infected orange fruits, to assess the ability of killer yeasts isolated from healthy orange fruits and leaves from orange orchards to control blue and green moulds and to evaluate the additive effect of BCAs in combination with 2% sodium bicarbonate (SBC), 2%, sodium benzoate (SB), 2% calcium chloride, 0.2% salicylic acid (SA) or 0.5% chitosan. Among eight fungi isolated from orange fruits showing symptoms of green and blue mulds infection, two were identified as P. digitatum and P. italicum and selected for in vitro assays. Twenty eight yeast isolates were obtained from orange leaves and from the surface of fruits. All yeasts exhibited high killer activity. Twelve yeasts reduced 22.5 –70% of P. digitatum growth while seven isolates reduced 21.1- 68.5% of P. italicum growth. The most potent yeast isolates were identified as Candida pseudotropicalis, Candida salmanticensis, Candida membranifaciens and Pichia guilliermondii. Combination of the BCAs, C. pseudotropicalis, C. salmanticensis and P. guilliermondii with SBC, CaCl2 or chitosan increased their effectiveness against P. digitatum. While combination of C. pseudotropicalis, C. membranifaciens and P. guilliermondii with these natural compounds decreased their effectiveness against P. italicum. Combination of C. membranifaciens with SA increased its effectiveness against P. digitatum. Sodium benzoate has additive effect on C. pseudotropicalis against P. digitatum and C. pseudotropicalis and P. guilliermondii against P. italicum

Prevalence rate of Klebsiella pneumoniae in the intensive care unit: epidemiology and molecular characteristics

Klebsiella pneumoniae carbapenemase producing bacteria are defined as a group of Gramnegative bacilli that are highly resistant to drugs. The resistance of pathogens of the Enterobacteriaceae family to β-lactam antibiotics such as carbapenems is considered a major threat in the medical field. The main aim of the current study was to explore and confirm the occurrence of carbapenemase producing K. pneumoniae in the Intensive Care Unit (ICU) in different hospital environment sample sites of two Egyptian hospitals in Cairo. Isolates were collected and the screening criteria of carbapenemase producing bacteria was followed by the investigators in order to record the antimicrobial resistance patterns of all isolates in addition to the molecular identification using the 16S rDNA. This study determined the sites responsible for the spreading of carbapenem-resistant K. pneumoniae including suction tubes, ventilator tubes, instrument tables and beds. All K. pneumoniae isolates collected from the ICU of both hospitals were resistant to oxacillin, meropenem and ceftazidime. Moreover, 16S rDNA gene sequence was used to study bacterial phylogeny and taxonomy for all K. pneumoniae isolates; the accession number of all isolates is reported. We concluded that infection control department policies in each hospital should be reinforced to avoid the escalation of K. pneumoniae as nosocomial infections in hospitals. This study should be repeated in other hospitals (especially the public hospitals) to assess the level of the problem

Serum soluble receptor of advanced glycation end products and risk of metabolic syndrome in Egyptian obese women

Obesity is one of the diagnostic criteria of metabolic syndrome (MS). It is correlated with insulin resistance (IR) and high vascular risk as well. Advanced glycation end products (AGEs) and their receptor (RAGE) play an important role in abnormal metabolic components in obese women. This study aimed to explore the serum levels of sRAGE in Egyptian obese women and compare with healthy non-obese controls and investigate the relationship between serum sRAGE, metabolic parameters, and obesity complications. The soluble form of receptor for advanced glycation end products (sRAGE), anthropometry, metabolic and biochemical biomarkers were measured in 100 obese women and 100 age-matched healthy control non-obese women. The homeostasis model assessment estimate of insulin resistance (HOMA-IR) has been determined from serum insulin and glucose values. Serum sRAGE levels were significantly lower in obese cases than controls and inversely correlated with obesity and metabolic parameters. Results of univariate and multivariate analyses for determinants of serum sRAGE levels in obese cases showed that parameters statistically and significantly related were body mass index (BMI), waist circumference (WC), LDL-C, TG, BP, HOMA-IR, ALT and AST. sRAGE is a novel biomarker for metabolic dysfunction in Egyptian obese women and might predict the future cardio-metabolic events

Cell progression of biofilm formation in Candida albicans and estimation of aspartic proteinase activity

Yeast cells are commonly used as powerful model system to study morphological phenotype and their processes. The study of morphogenesis of different modes of growth in yeast during biofilm development is an important issue. Cell progression is important tool to understand morphological transition and virulence in C. albicans. Biofilm formation and aspartic proteinase activity are two major important virulence factors associated with the pathogenicity of C. albicans. This study aimed to highlight the formation of biofilm, monitor the development of biofilm progression and estimate the activity of aspartic proteinase. Biofilm formation was assessed by Eliza plate and monitored at different pH values, different incubation time and different media. Biofilm development was visualized microscopically. Cell division and mitotic phases in yeast cells were studied and photographed. The production of aspartic proteinase was assessed by bovine serum albumin agar plates and evaluated at different pH values and different incubation time intervals. Results revealed that C. albicans was positive for biofilm formation and aspartic proteinase production. pH and different media had marked significant effect on biofilm formation. Additionally, the transition from simple yeast budding form to a complex filament structure was time dependent. Moreover, pH showed significant effect on aspartic proteinase activity

The Validity of Body Adiposity Indices in Predicting Metabolic Syndrome and Its Components among Egyptian Women

AIM: To assess the associations between the body adiposity indices and risk of metabolic syndrome (MS) and its components in Egyptian women and to evaluate their predictive power.MATERIALS AND METHODS: This was a cross-sectional analysis performed on 180 Egyptian women aged between 25-35 years. They were 90 women with MS diagnosed by International Diabetes Federation (IDF) and 90 healthy age matched controls. Body adiposity index (BAI), body mass index (BMI), waist to hip ratio (WHR) and waist to height ratio (WHtR) were calculated and serum samples were analyzed for metabolic parameters. Receiver operating characteristic curves (ROC) was used to determine the discriminatory capacity of BAI, WHR WHtR and BMI for MS.RESULTS: Area under the curve (AUC) was highest for BIA, followed by WHR, WHtR and then BMI. All adiposity indices were significantly correlated with metabolic components and BAI had the highest correlation coefficients compared to other indices.CONCLUSION: BAI is a practical predictor for MS and has satisfactory diagnostic accuracy for diagnosing MS among Egyptian women and can be used in addition to WHR, WHtR and BMI for identifying MS in the field studies

Association of the Pro12Ala Polymorphism with the Metabolic Parameters in Women with Polycystic Ovary Syndrome

AIM: To investigate the association of peroxisome proliferator-activated receptor gamma (PPARG) Pro12Ala polymorphism with polycystic ovary syndrome (PCOS) and its effect on the metabolic parameters in PCOS women.METHODS: The study used PCR to identify the presence of the PPARG Pro12Ala polymorphism in 100 PCOS women and 120 age-matched healthy women. All participants were subjected to anthropometry, biochemical and metabolic evaluation.RESULTS: Significant difference in the genotypes distributions of PPARG Pro12Ala polymorphism was observed among PCOS women and controls (p = 0.03). The frequency of the polymorphic allele Ala was significantly higher in PCOS cases than that in the controls (OR = 2.01, p = 0.01). The carries of the variant allele Ala in PCOS women showed significant higher values in body mass index (BMI), systolic and diastolic blood pressure, waist circumference, waist to hip ratio, sum of skin folds, fasting blood glucose, fasting blood insulin, HOMA-IR, fasting triglycerides, total cholesterol and low-density lipoprotein than non-carriers.CONCLUSION: The PPARG Pro12Ala polymorphism might contribute to the risk of PCOS and abnormal metabolic parameters and could be considered as a biomarker for early diagnosis and clinic prediction of metabolic complications