Effect of lycoriside,an acylglucosyloxy alkaloid,on mast cells

The effect of lycoriside, an acylglucosyloxy alkaloid from Crinum asiaticum Linn, (family Amaryllidaceae), with or without sitosterol-3-O--D-glucoside, was studied on the rate of degranulation of peritoneal mast cells of albino rats. Lycoriside, at lower concentrations (1–20 µg/ml), in vitro, produced statistically significant protection against Tween 80-induced degranulation, as also to sensitized mast cells challenged with an antigen (horse serum). It also provided protection against compound 48/80-induced degranulation of mast cells when administered in vivo (1–5 mg/kg, po). At higher concentrations (100 µg/ml and above), in vitro, however, it had a mast-cell degranulation effect per se. The addition of sitosterol-3-O--D-glucoside to lycoriside did not modify the effect of the latter compound. The mechanism of the dual response elicited by lycoriside is appraised in view of a concentration-dependent anti- or prerelease effect on mast-cell mediators.     

A brief review of mRNA therapeutics and delivery for bone tissue engineering

The therapeutics for bone tissue regeneration requires constant advancements owing to the steady increase in the number of patients suffering from bone-related disorders, and also to find efficient and cost-effective treatment modalities. One of the major advancements in the field of therapeutics is the development of mRNAs. mRNAs, which have been extensively tested for the vaccines, could be very well utilized as a potential inducer for bone regeneration. The ability of mRNAs to enter the cells and instruct the cellular machinery to produce the required native proteins such as BMP or VEGF is a great way to avoid the issues faced with growth factor deliveries such as the production cost, loss of biological function etc. However, there have been a few hurdles for using mRNAs as an effective therapeutic agent, such as proper dosing, tolerating the degradation by RNases, improving the half-life, controlling the spatio-temporal release and reducing the off-target effects. This brief review discusses the various developments in the field of mRNA therapeutics especially for bone tissue engineering, how nano-formulations are being developed to effectively deliver the mRNAs into the cells by evading the immune responses, how researchers have developed certain strategies to increase the half-life, to successfully deliver the mRNAs to specific bone defect area and bring about effective bone regeneration.

This review provides an update on the various mRNA preparations, carriers that can deliver these preparations and how they could potentially enhance the bone regeneration.     

Effects of the advent of disease on smoking habit

A study was undertaken to determine the effect of the development or disease on patients' smoking habits. Interviews with 841 subjects (591 smokers) were conducted following a standard protocol. Of the 841 subjects, 96 (61 smokers) had hydroceles or hernias and were considered a control group; the remainder had neoplastic diseases, respiratory disorders, diabetes, cardiovascular diseases, psychiatric illnesses, peripheral vascular diseases, and gastrointestinal and liver disorders. Patients with cardiovascular, pulmonary, and neoplastic diseases, diabetes, gastrointestinal diseases, and cirrhosis of the liver significantly reduced or stopped smoking because of medical advice (19%), socioeconomic factors (8%), or aggravation of disease (24%). The advent of disease was associated with an increase in smoking in several patients (including 2 with bronchial asthma and 12 with peripheral vascular disease) because of the apparent belief that smoking is beneficial in overcoming the disease or in controlling pain. Additional long-term studies are needed to explore the relationship between disease and smoking habits.     

Curcumin ameliorates cardiac inflammation in rats with autoimmune myocarditis

Curcumin is a natural polyphenolic compound abundant in the rhizome of the perennial herb turmeric, Curcuma longa. It is commonly used as a dietary spice and coloring agent in cooking, and is used anecdotally as an herb in traditional Indian and Chinese medicine. It has been reported that curcumin has the potential to protect against cardiac inflammation through suppression of GATA-4 and nuclear factor-κB (NF-κB); however, no study to date has addressed the effect of curcumin on experimental autoimmune myocarditis (EAM) in rats. In this study, 8-week-old male Lewis rats were immunized with cardiac myosin to induce EAM. They were then divided randomly into a treatment or vehicle group and orally administrated curcumin (50 mg/kg/d) or 1% gum arabic, respectively, for 3 weeks after myosin injection. We performed hemodynamic, echocardiographic, hematoxylin and eosin staining, mast cell staining and Western blotting studies to evaluate the protective effect of curcumin in the acute phase of EAM. Cardiac functional parameters measured by hemodynamic and echocardiographic studies were significantly improved by curcumin treatment. Furthermore, curcumin reduced the heart weight-to-body weight ratio, area of inflammatory lesions and the myocardial protein level of NF-κB, interleukin (IL)-1β, tumor necrosis factor (TNF)-α and GATA-4. Our results indicate that curcumin has the potential to protect against cardiac inflammation through suppression of IL-1β, TNF-α, GATA-4 and NF-κB expresses, and may provide a novel therapeutic strategy for autoimmune myocarditis.     

Modulation of AT-1R/AMPK-MAPK cascade plays crucial role for the pathogenesis of diabetic cardiomyopathy in transgenic type 2 diabetic (Spontaneous Diabetic Torii) rats

There are evidences that the activation of AMPK is playing pivotal role in the lipid and glucose metabolism. It has been reported that both the AMPK and angiotensin-II acts as a negative regulator for each protein. It has been well proven that the MAPK cascade could be modulated by the presence of angiotensin-II. Moreover, studies were shown that p38 MAPK stimulates glucose uptake through the AMPK activation. Therefore, we speculate and tried to demonstrate that the modulation of AT-R/MAPK pathway through AMPK might play crucial roles for the pathogenesis of diabetic cardiomyopathy, using the transgenic (Spontaneous Diabetic Torii-SDT) rats. We performed Western blot analysis for the measurement of myocardial AT-R, AMPK and MAPK cascades-related protein expressions, p67-phox and caspase-12. In addition, we employed dihydroethidium (DHE), Azan Mallory and hemotoxylin eosin (HE) staining methods to demonstrate the superoxide radical production, fibrosis and hypertrophy, respectively. The protein expressions, such as AT-1R, p-ERK1/2, p67-phox and caspase-12 were found to be significantly increased and conversely, the Ang-(1-7) mas R, Tak1, LKB1 and p-AMPKα1, p-p38 MAPK and p-JNK protein expressions were found to be considerably decreased in the SDT rats, in comparison to the normal rats. The DHE, Azan Mallory and HE stainings also revealed that the SDT rats have more superoxide radical production, fibrosis and hypertrophy, respectively than the normal rats. Taken together, it is suggested that the modulation of AT-1R/AMPK-MAPK pathway might play crucial roles for the pathogenesis of diabetic cardiomyopathy and it could become an important therapeutic target to ameliorate the diabetic cardiomyopathy.     

Bacteriological and pathological studies of egg peritonitis in commerciallayer chicken in Namakkal area

Objective

To detect the various bacteriological agents and pathological changes in commercial layer chicken affected with egg yolk peritonitis in Namakkal region of India.

Methods

A total of 6 572 layer chicken from 85 commercial farms were subjected for the study, out of which 1 715 showed various types of oviduct abnormalities. Among the 1 715, 264 birds from six farms were identified as egg peritonitis on the basis of postmortem examination. Trachea, lung, heart blood, liver, peritoneal exudate, oviduct (infundibulum, magnum, uterus) and cloacal swabs were collected from the 264 birds with egg peritonitis lesion for screening of bacterial agents. Signalment, clinical signs and pathological changes were recorded in the affected flocks.

Result

The results of the present investigation indicated that the E. coli associated egg peritonitis was responsible for 15.39% of the reproductive tract abnormalities in commercial layers between 21 and 80 week of age. In the affected flocks egg production drop and mortality varied from 3% to 20% and 0.5% to 7.0% respectively. It was noticed during peak egg production (21 to 60 week) and southwest monsoon season (58%). Statistical analysis of age, season and egg production by Chi square test of independence revealed highly significant difference. E. coli was isolated as a pure culture and concurrent with other bacterial agents in 226 and 38 birds respectively. Among the fifteen E. coli serotypes identified serotype O₁₆₆, O₆₄ and O₁₁₁ were predominant. Necropsy examination of affected birds revealed the presence of amorphous or insipissiated yolk material in the abdominal cavity with inflammatory changes in the ovary, oviduct and intestine. Microscopically the oviduct surface epithelium showed degeneration and desquamation, moderate to marked infiltration of inflammatory cells especially heterophils and lymphocytes in various regions and lumen contained serofibrinous exudate, inflammatory and desquamated epithelial cells with bacterial microcolonies. Ovarian follicles revealed hyperemia, degeneration of granulosa cells and infiltration of inflammatory cells. Intestine showed degenerative, necrotic and inflammatory lesion.

Conclusion

The findings of this study showed that the egg peritonitis might be caused by either the translocation of intestinal E. coli into the peritoneal cavity or by the movement of cloacal E. coli into the oviduct followed by ascension of these bacteria up the oviduct, through the infundibulum, and into the peritoneal cavity. To control the egg peritonitis faecal contamination with E. coli should be minimized.     

Retrospective cohort study investigating extent of pertussis transmission during a boarding school outbreak,England, December 2017 to June 2018

On 1 May 2018, a pertussis outbreak was declared and widespread vaccination recommended at an all-female secondary boarding school in southern England. We conducted a retrospective cohort study to determine the extent of pertussis transmission and identify risk factors in this semi-closed population. Of 504 students and staff assessed before post-exposure vaccination, 48% (n = 240) had evidence of pertussis. A sub-analysis of 409 students found that both residential dormitory (p = 0.05) and school year (p = 0.03) were associated with pertussis, with odds decreasing by 11% for each increase in school year (95% confidence interval: 0.7–20.2). Odds of pertussis were 1.7 times higher in those assumed to have received acellular vaccines for their primary course compared with those assumed to have received whole-cell vaccines (based on date of birth), although this difference was not significant (p = 0.12). Our findings support the need for timely, widespread vaccination following identification of cases among adolescents in a semi-closed United Kingdom (UK) setting and to review the evidence for the introduction of an adolescent pertussis booster to the UK routine vaccination programme.     

Adverse Events of Interest Following Influenza Vaccination in the First Season of Adjuvanted Trivalent Immunization: Retrospective Cohort Study

BackgroundVaccination is the most effective form of prevention of seasonal influenza; the United Kingdom has a national influenza vaccination program to cover targeted population groups. Influenza vaccines are known to be associated with some common minor adverse events of interest (AEIs), but it is not known if the adjuvanted trivalent influenza vaccine (aTIV), first offered in the 2018/2019 season, would be associated with more AEIs than other types of vaccines.ObjectiveWe aim to compare the incidence of AEIs associated with different types of seasonal influenza vaccines offered in the 2018/2019 season.MethodsWe carried out a retrospective cohort study using computerized medical record data from the Royal College of General Practitioners Research and Surveillance Centre sentinel network database. We extracted data on vaccine exposure and consultations for European Medicines Agency–specified AEIs for the 2018/2019 influenza season. We used a self-controlled case series design; computed relative incidence (RI) of AEIs following vaccination; and compared the incidence of AEIs associated with aTIV, the quadrivalent influenza vaccine, and the live attenuated influenza vaccine. We also compared the incidence of AEIs for vaccinations that took place in a practice with those that took place elsewhere.ResultsA total of 1,024,160 individuals received a seasonal influenza vaccine, of which 165,723 individuals reported a total of 283,355 compatible symptoms in the 2018/2019 season. Most AEIs occurred within 7 days following vaccination, with a seasonal effect observed. Using aTIV as the reference group, the quadrivalent influenza vaccine was associated with a higher incidence of AEIs (RI 1.46, 95% CI 1.41-1.52), whereas the live attenuated influenza vaccine was associated with a lower incidence of AEIs (RI 0.79, 95% CI 0.73-0.83). No effect of vaccination setting on the incidence of AEIs was observed.ConclusionsRoutine sentinel network data offer an opportunity to make comparisons between safety profiles of different vaccines. Evidence that supports the safety of newer types of vaccines may be reassuring for patients and could help improve uptake in the future.     

Oral Fluid Testing for Pertussis,England and Wales,June 2007–August 2009

Existing pertussis surveillance systems tend to underidentify less severe cases among older children and adults. For routine follow-up of notified, nonconfirmed, clinically diagnosed pertussis cases, use of an oral fluid test was pilot tested in England and Wales during June 2007–August 2009. During that period, 1,852 cases of pertussis were confirmed by established laboratory methods and another 591 by oral fluid testing only. Although introduction of serologic testing in 2002 led to the greatest increase in ascertainment of pertussis, oral fluid testing increased laboratory ascertainment by 32% overall; maximal increase (124%) occurred among children 5–9 years of age. Patients whose pertussis was confirmed by oral fluid testing were least likely to be hospitalized, suggesting that milder community cases were being confirmed by this method. Oral fluid testing is an easily administered, noninvasive surveillance tool that could further our understanding of pertussis epidemiology and thereby contribute to decisions on vaccination strategies.Existing surveillance systems for pertussis are incomplete and tend to be biased toward identifying severe cases in infants (1,2), as reflected by extremely high reported incidence for this age group (3–5). Underascertainment of cases in older patients is well recognized because of a combination of factors, including reduced likelihood that patients with milder symptoms will seek health care, underdiagnosis for patients who do seek health care, and underreporting (6–9). Although these persons usually experience milder disease, often without classic signs and symptoms, some become substantially ill (9) and can still infect vulnerable infants. Additional test methods that provide adequate sensitivity and specificity and that are acceptable to health professionals and patients could therefore improve ascertainment of pertussis and provide data that are more representative of disease within the population.Since the early 1960s, Bordetella pertussis has been isolated from the nasopharynx by use of conventional microbiological techniques. However, culture requires that a specimen be collected early in the illness and might lack sensitivity because the organism is delicate and any delay in processing specimens can reduce the probability of isolation (10). Isolation of the organism is more difficult if the patient has been vaccinated, if the patient has received antimicrobial drugs, and if too much time has gone by since onset of cough. PCR testing for the presence of B. pertussis DNA in nasopharyngeal samples is more sensitive than culture because the organism does not need to be viable (11). PCR sensitivity, however, decreases substantially with increasing patient age and duration of symptoms (12). Serologic testing has been established as a diagnostic method complementary to PCR, and recommendations by European Union reference laboratories for such assays have been described (13). Serologic testing is used in at least 20 European countries (14) (including the United Kingdom since 2002), Japan, and Australia to diagnose infection in patients who have been coughing for at least 2 weeks, when culture and PCR are less likely to yield positive results (10) as has been demonstrated in certain studies (15). Serologic testing has been used predominantly for older children and adults who tend to seek care later (5).The Health Protection Agency (HPA; which became Public Health England on April 1, 2013) Respiratory and Systemic Infection Laboratory (which became the Respiratory and Vaccine Preventable Reference Unit on April 1, 2013) developed an ELISA to detect IgG against pertussis toxin in oral fluid (16). This test was intended to act as a surrogate for the serum antibody assay. Oral fluid sampling is appealing because collection is straightforward; it is noninvasive (oral fluid is collected from around the gum line by using an absorbent swab) and can be collected by the patient or parent/guardian in the home and mailed to the laboratory for testing. The oral fluid assay detects seropositivity with a sensitivity of 79.7% (95% CI 68.3%–88.4%) and a specificity of 96.6% (95% CI 91.5%–99.1%) (16). Thus, oral fluid titers of >70 arbitrary units have a positive predictive value of 76.2%–93.2% for pertussis among children with chronic cough when used as a surrogate for the serum ELISA, assuming disease prevalence of 12%–37% (which includes the lower and upper limits of disease prevalence shown by other studies) (17).Similar oral fluid antibody tests have been developed by HPA as surrogates for serologic testing for measles, mumps, and rubella (18,19). Oral fluid testing of patients after their formal notification of clinically diagnosed measles, mumps, and rubella has been conducted in England and Wales since 1994; this test has been acceptable and is used to augment routine serologic diagnosis for these diseases (18). After completion of a successful small-scale study in 2 areas of England (20), it was decided to conduct a national pilot test for the use of oral fluid testing for pertussis as a similar surveillance tool to obtain laboratory confirmation of pertussis cases statutorily notified on the basis of clinical diagnosis. Oral fluid testing was chosen because of the ease of sample collection and the predicted increased patient compliance with use of a noninvasive testing method. All laboratory-confirmed cases of pertussis are coordinated on a national basis, and each is followed up by asking the Health Protection Units (HPUs) or patients’ general practitioners to complete a detailed surveillance questionnaire.The aim of this national oral fluid surveillance was to improve case ascertainment and representativeness, increase rates of confirmation of notified cases, and provide more detailed information on notified cases of pertussis (if confirmed) via the surveillance questionnaire. Such improvements would strengthen the evidence base for vaccination policy decision making. We compared the effects of oral fluid testing as a notification follow-up service over the 27 months that it was available with effects during a comparable 27 months before its availability.