Evaluation of immunomodulatory activity of tenoxicam in mice

Purpose: The present study was conducted to evaluate the effect of tenoxicam on cellular and humoral immunity.Methods: Tenoxicam (2.5 - 10mg/kg) was administered at three different doses to three groups of mice and the cellular immune responses were studied using delayed hypersensitivity response (DTH) and cyclophosphamide-induced neutropenia while the humoral immune response was evaluated using hemagglutination test and mice mortality ratio. Normal saline and cyclophosphamide were used as negative and positive controls, respectively.Results: DTH assay resulted in a significant reduction in skin thickness (p < 0.05) for tenoxicam treated groups when compared to the negative control group at 24 h, 48 h and 72 h after administration of challenging dose of dinitrochlorobenzene (DNCB). Cyclophoshamide induced neutropenia showed a significant percentage reduction in total leukocyte count (TLC) and differential leukocyte count (DLC) i.e. lymphocytes and neutrophils (p< 0.05), but an increase in monocytes in all the treatment groups in the following order: 10 mg>5 mg >2.5 mg> negative control group. A dose dependent reduction response was observed (p<0.05) in haemagglutination assay (HA). In mice lethality test mortality ratios of 2.5 mg, 5 mg, 10 mg tenoxicam were 60 %, 80% and 100 %, respectively, compared to 20 % and 100 % for normal saline group and cyclophosphamide, respectivelyConclusion: The results suggest that tenoxicam suppresses both cellular and humoral immunity in mice.Keywords: Tenoxicam, Cellular immunity, Humoral immunit

The Efficacy of Infrared Light Therapy in the Treatment of Onychomycosis

Objective: To study the efficacy of Infrared light therapy in treating Onychomycosis. Study Design: Cross-sectional study. Place and Duration of Study: Department of Dermatology, Combined Military Hospital, Bahawalpur Pakistan, from Jan to Jul 2022. Methodology: A total of 122 patients of either gender with Onychomycosis were included in the study. Sessions with infrared light (24W Red Bulb, 660nm-850nm wavelength) were arranged once a week. The total duration of therapy consisted of four weeks in the case of fingernails and eight weeks in the case of toenails. Patients were called for follow-up at the end of the first, second, and third months after completion of treatment for efficacy evaluation. Results: The mean duration of complaints was 9.12±2.58 weeks, and the mean weight of patients was 84.11±8.38Kg. Male patients were 36(29.5%), and females were 86(70.5%). 98(80.3%) patients had toenail involvement, and 24(19.7%) patients had fingernail involvement. Efficacy was defined as 2/3rd (66.0%) clearance of the nail plate after 90 days of completion of treatment from the first observation at the time of presentation on visual examination. Efficacy in our study was observed in 25(20.5%) patients. Conclusion: Our study concluded that infrared light therapy is an effective treatment modality for Onychomycosis

Safety and efficacy of ketamine xylazine along with atropine anesthesia in BALB/c mice

Anesthetics are an indispensable prerequisite for surgical intervention and pharmacological animal studies. The objective of present study was to optimize the dose of ketamine (K) and xylazine (X) along with atropine sulfate (A) in order to achieve surgical tolerance in BALB/c mice. Several doses of ketamine (100, 150, 200 mg/kg) and xylazine (10, 15, 20 mg/kg) were mixed and combination of nine doses (K/X: 100/10, 100/15, 100/20, 150/10, 150/15, 150/20, 200/10,200/15,200/20) were evaluated (n=9 per combination). A constant dose of atropine (0.05 mg/kg) was also used to counter side effect. Timerelated parameters were evaluated on the basis of reflexes. KX at dose 200/20 mg/kg produced surgical tolerance in all nine mice with duration 55.00±6.87 minutes. The induction time 0.97±0.09 minutes, sleeping time 90.67±5.81 minutes and immobilization time (102.23±6.83 minutes) were significantly higher than all combination. However, this combination was considered unsafe due to 11 % mortality. While, KX at dose 200/15 mg/kg results in none of the mortality, so was considered as safe. Moreover, this combination produces surgical tolerance in 89 % mice with duration (30.00±7.45 minutes). It was concluded that KX at dose 200/15 mg/kg along with atropine 0.05 mg/kg is safe for performing surgical interventions in BALB/c mice

A comparative absorption study of sucrosomial® orodispersible vitamin D3 supplementation vs. a reference chewable tablet and soft gel capsule vitamin D3 in improving circulatory 25(OH)D levels in healthy adults with vitamin D deficiency—Results from a prospective randomized clinical trial

BackgroundVitamin D (Vit D) deficiency (VDD), associated with diverse health conditions, is commonly treated with Vit D3 supplements. However, the gastrointestinal (GI) absorption of Vit D3 in different formulations has not been well studied.ObjectiveWe aimed to compare the absorption of an innovative phospholipids-sucrester matrix biodelivery vehicle-based (sucrosomial®) orodispersible Vit D3 preparation against a reference chewable tablet and soft gel capsule (SGC) Vit D3 formulations in Vit D-deficient healthy adults.MethodsIn study 1, 25 subjects were randomized to receive a weekly single dose of 200,000 IU of sucrosomial® Vit D3 (n = 12) or chewable tablet Vit D3 (n = 13) for 3 weeks. In study 2, 20 subjects were randomized to receive a single dose of 200,000 IU every other week of sucrosomial® Vit D3 (n = 10) or SGC Vit D3 (n = 10) for 6 weeks. Circulatory 25-hydroxyvitamin D3 [25(OH)D] levels were reassessed after 2, 3, and 6 weeks in study 1 and after 4 and 6 weeks in study 2.ResultsIn study 1, after 2 weeks, circulatory 25(OH)D levels increased significantly in both Vit D3 treatment groups (p < 0.0001) but improved markedly in the sucrosomial® Vit D3 group, with no further considerable change after 3 and 6 weeks in both groups. Overall, at all three follow-ups, sucrosomial® Vit D3 treatment achieved significantly higher and sustained 25(OH)D levels (p < 0.001). In study 2, after 4 weeks, both Vit D3 treatment groups showed significant improvement in circulatory 25(OH)D levels (p < 0.0001) but substantially higher in the sucrosomial® group with statistically significant differences between the two treatment groups (p = 0.02). At the 6-week follow-up, only subjects in the sucrosomial® Vit D3 group showed a further increase in circulatory 25(OH)D levels (p = 0.049), but no further significant changes in the levels of the SGC Vit D3 group (p = 0.062), showing a statistically significant difference between the two treatment groups (p = 0.002). The Vit D3 treatment was well tolerated by all participants, and no treatment-emergent effects or serious adverse events were reported.ConclusionOur results suggest that the sucrosomial® Vit D3 preparation absorbs efficiently in the GI system, achieving adequately higher and sustained circulatory Vit D levels in VDD, and thus can effectively contribute to the body protection against VDD-associated health conditions.Clinical trial registrationclinicaltrials.gov, identifier: NCT05706259

Effects of a high-dose 24-h infusion of tranexamic acid on death and thromboembolic events in patients with acute gastrointestinal bleeding (HALT-IT): an international randomised, double-blind, placebo-controlled trial

Background: Tranexamic acid reduces surgical bleeding and reduces death due to bleeding in patients with trauma. Meta-analyses of small trials show that tranexamic acid might decrease deaths from gastrointestinal bleeding. We aimed to assess the effects of tranexamic acid in patients with gastrointestinal bleeding. Methods: We did an international, multicentre, randomised, placebo-controlled trial in 164 hospitals in 15 countries. Patients were enrolled if the responsible clinician was uncertain whether to use tranexamic acid, were aged above the minimum age considered an adult in their country (either aged 16 years and older or aged 18 years and older), and had significant (defined as at risk of bleeding to death) upper or lower gastrointestinal bleeding. Patients were randomly assigned by selection of a numbered treatment pack from a box containing eight packs that were identical apart from the pack number. Patients received either a loading dose of 1 g tranexamic acid, which was added to 100 mL infusion bag of 0·9% sodium chloride and infused by slow intravenous injection over 10 min, followed by a maintenance dose of 3 g tranexamic acid added to 1 L of any isotonic intravenous solution and infused at 125 mg/h for 24 h, or placebo (sodium chloride 0·9%). Patients, caregivers, and those assessing outcomes were masked to allocation. The primary outcome was death due to bleeding within 5 days of randomisation; analysis excluded patients who received neither dose of the allocated treatment and those for whom outcome data on death were unavailable. This trial was registered with Current Controlled Trials, ISRCTN11225767, and ClinicalTrials.gov, NCT01658124. Findings: Between July 4, 2013, and June 21, 2019, we randomly allocated 12 009 patients to receive tranexamic acid (5994, 49·9%) or matching placebo (6015, 50·1%), of whom 11 952 (99·5%) received the first dose of the allocated treatment. Death due to bleeding within 5 days of randomisation occurred in 222 (4%) of 5956 patients in the tranexamic acid group and in 226 (4%) of 5981 patients in the placebo group (risk ratio [RR] 0·99, 95% CI 0·82–1·18). Arterial thromboembolic events (myocardial infarction or stroke) were similar in the tranexamic acid group and placebo group (42 [0·7%] of 5952 vs 46 [0·8%] of 5977; 0·92; 0·60 to 1·39). Venous thromboembolic events (deep vein thrombosis or pulmonary embolism) were higher in tranexamic acid group than in the placebo group (48 [0·8%] of 5952 vs 26 [0·4%] of 5977; RR 1·85; 95% CI 1·15 to 2·98). Interpretation: We found that tranexamic acid did not reduce death from gastrointestinal bleeding. On the basis of our results, tranexamic acid should not be used for the treatment of gastrointestinal bleeding outside the context of a randomised trial

The role of extracellular polymeric substances in Pseudomonas aeruginosa biofilm architecture : a thesis presented in partial fulfilment of the requirements for the degree of Doctor of Philosophy in Microbiology at Massey University, Palmerston North, New Zealand

Pseudomonas aeruginosa is an opportunistic pathogen. It causes chronic lung infections in the cystic fibrosis patients. These infections become highly resistant to antibacterial treatments. Bacteria develop this resistance because they become protected inside biofilms. Biofilms are microbial communities enmeshed in a partially self-produced and partially recruited, impregnable extracellular matrix. The matrix is composed of extracellular DNA, proteins, lipids and exopolysaccharides. The exopolysaccharides play an imperative role in architecture of the biofilm matrix. P. aeruginosa produces three distinct exopolysaccharides; Psl, Pel and alginate. In this study, non-mucoid strain PAO1 and mucoid (producing excessive alginate) strain PDO300 of P. aeruginosa were used to generate mutants deficient in one or more exopolysaccharides. Role of these three exopolysaccharides in biofilm formation was investigated. Results showed that the absence of alginate altered the architecture of biofilms in PDO300 as well as in PAO1, when compared to biofilms formed by the respective parent strains. Psl was found indispensable for mushroom-like shape of the biofilms in both strains. Pel was required for the compactness of the biofilms, but PAO1 formed mushroom-like structures even in the absence of Pel. However, Pel-deficient PDO300 did not form mature biofilm, suggesting differential role of Pel in the two strains. Psl-only as well as Pel-only, producing mutants were able to formed multilayer biofilm. Production of one type of exopolysaccharide appeared to influence production of the other types of exopolysaccharide. Psl-deficient mutants increased the production of Pel, while Pel-deficient mutants showed a ten-fold increase in the production of alginate. Furthermore, absence of negatively charged alginate in the biofilm was compensated by eDNA. Regulation of exopolysaccharide biosynthesis operons showed a high expression of psl operon in PAO1, whereas its expression in PDO300 was surprisingly low and confined to a few cells near the base. A high and uniform expression of the algD operon in PDO300 was observed at all times during biofilm development. A low expression of algD operon was also detected in PAO1. Expression of the pel operon was confined to the stalk of PDO300 and PAO1. The role of PelF, the only glycosyltransferase encoded by pel operon, in Pel biosynthesis was investigated and found to be a soluble glycosyltransferase which uses UDP-glucose towards Pel biosynthesis. Site directed mutagenesis revealed that conserved R-325 and K-330 were essential for the PelF activit

Immunomodulatory activities of gemifloxacin in mice

Objective(s):Gemifloxacin is a broad spectrum antibiotic and has shown excellent coverage against a wide variety of microorganisms. In this study, an attempt was made to evaluate the immunomodulatory potential of gemifloxacin in male swiss albino mice in vivo. Materials and Methods: Three doses of gemifloxacin 25 mg/kg, 50 mg/kg and 75 mg/kg were used intraperitoneally (IP) for the evaluation of immune responses in mice. Delayed type hypersensitivity (DTH), heamagglutination assay, jerne hemolytic plaque formation assay and cyclophosphamide induced neutropenia assay were performed to evaluate the effect of gemifloxacin on immune responses. Results: DTH assay has shown the significant immune suppressant potential of gemifloxacin at 25 mg/kg dose and 75mg/kg dose. Total leukocyte count (TLC) has shown decrease in leukocyte count (

Factors affecting the efficiency of equine embryo transfer (EET) in polo mares under subtropical conditions of Pakistan.

Equine embryo transfer (EET) is a prominent technology in the equine breeding industry, and its efficacy is affected by a number of factors. The current study aimed to determine the effects of the breed of donor/recipient mares, estrus/ovulation induction treatment, cooled transportation of embryos, and synchrony between donor and recipient mares on the efficiency of the EET under subtropical conditions of Pakistan. A total of eighty-four (n = 84) Polo-playing donor mares (Argentino-polo = 41 and Anglo-Arab = 43) and seventy (n = 70) recipient mares (light breed = 26 and heavy breed = 44) were used for EET. The donor mares exhibiting natural estrus (n = 28) were detected by teaser a stallion, and corpus luteum (CL) having mares (n = 56) were treated with prostaglandin (150 μg of Cloprostenol) for estrus induction. The mares' follicular growth was monitored through ultrasonography until the dominant follicle's size reached 35 mm or more with a moderate to obvious uterine edema score. Afterward, the mares were treated either with GnRH, i.e., 50 μg of Lecirelin acetate (n = 41) or Ovusyn, i.e., 1500 IU hCG (n = 43). Insemination with chilled semen was performed 24 hours later. The embryos were collected non-surgically, 7 or 8 days after ovulation, from the donor mares. The collected embryos were transferred into the well-synchronized recipient mares as fresh (n = 44) or chilled (n = 26) embryos. The pregnancy after ET was checked through ultrasonography. Statistical analysis revealed that the embryo recovery rate (ERR) remained significantly higher (P0.05) affect the ERR. There was no significant effect of the type (fresh vs chilled), classification, and stage of development of embryo on pregnancy outcomes (P>0.05). ET pregnancy rate was significantly affected by the breed of recipient mares and ovulation synchrony between donor and recipient mares (P<0.05). In conclusion, under the subtropical conditions of Pakistan, PG-based estrus induction of donor mares, breed of recipient mares, and ovulation synchrony between the donor and recipient mares had a substantial effect on the efficiency of EET