Bone deficits in children and youth with type 1 diabetes: A systematic review and meta-analysis.

Deficits in bone mineral and weaker bone structure in children with type 1 diabetes (T1D) may contribute to a lifelong risk of fracture. However, there is no meta-analysis comparing bone properties beyond density between children with T1D and typically developing children (TDC). This meta-analysis aimed to assess differences and related factors in bone mineral content (BMC), density, area, micro-architecture and estimated strength between children with T1D and TDC. We systematically searched MEDLINE, Embase, CINAHL, Web of Science, Scopus, Cochrane Library databases, and included 36 in the meta-analysis (2222 children and youth with T1D, 2316 TDC; mean age ≤18 yrs., range 1-24). We estimated standardized mean differences (SMD) using random-effects models and explored the role of age, body size, sex ratio, disease duration, hemoglobin A1c in relation to BMC and areal density (aBMD) SMD using meta-regressions. Children and youth with T1D had lower total body BMC (SMD: -0.21, 95% CI: -0.37 to -0.05), aBMD (-0.30, -0.50 to -0.11); lumbar spine BMC (-0.17, -0.28 to -0.06), aBMD (-0.20, -0.32 to -0.08), bone mineral apparent density (-0.30, -0.48 to -0.13); femoral neck aBMD (-0.21, -0.33 to -0.09); distal radius and tibia trabecular density (-0.38, -0.64 to -0.12 and -0.35, -0.51 to -0.18, respectively) and bone volume fraction (-0.33, -0.56 to -0.09 and -0.37, -0.60 to -0.14, respectively); distal tibia trabecular thickness (-0.41, -0.67 to -0.16); and tibia shaft cortical content (-0.33, -0.56 to -0.10). Advanced age was associated with larger SMD in total body BMC (-0.13, -0.21 to -0.04) and aBMD (-0.09; -0.17 to -0.01) and longer disease duration with larger SMD in total body aBMD (-0.14; -0.24 to -0.04). Children and youth with T1D have lower BMC, aBMD and deficits in trabecular density and micro-architecture. Deficits in BMC and aBMD appeared to increase with age and disease duration. Bone deficits may contribute to fracture risk and require attention in diabetes research and care. STUDY REGISTRATION: PROSPERO (CRD42020200819).

Tigecycline antibacterial activity, clinical effectiveness, and mechanisms and epidemiology of resistance: narrative review.

Tigecycline is unique glycylcycline class of semisynthetic antimicrobial agents developed for the treatment of polymicrobial infections caused by multidrug-resistant Gram-positive and Gram-negative pathogens. Tigecycline evades the main tetracycline resistance genetic mechanisms, such as tetracycline-specific efflux pump acquisition and ribosomal protection, via the addition of a glycyclamide moiety to the 9-position of minocycline. The use of the parenteral form of tigecycline is approved for complicated skin and skin structure infections (excluding diabetes foot infection), complicated intra-abdominal infections, and community-acquired bacterial pneumonia in adults. New evidence also suggests the effectiveness of tigecycline for the treatment of severe Clostridioides difficile infections. Tigecycline showed in vitro susceptibility to Coxiella spp., Rickettsia spp., and multidrug-resistant Neisseria gonnorrhoeae strains which indicate the possible use of tigecycline in the treatment of infections caused by these pathogens. Except for intrinsic, or often reported resistance in some Gram-negatives, tigecycline is effective against a wide range of multidrug-resistant nosocomial pathogens. Herein, we summarize the currently available data on tigecycline pharmacokinetics and pharmacodynamics, its mechanism of action, the epidemiology of tigecycline resistance, and its clinical effectiveness.

Microbiological Detoxification of Mycotoxins: Focus on Mechanisms and Advances.

Some fungal species of the genera Aspergillus, Penicillium, and Fusarium secretes toxic metabolites known as mycotoxins, have become a global concern that is toxic to different species of animals and humans. Biological mycotoxins detoxification has been studied by researchers around the world as a new strategy for mycotoxin removal. Bacteria, fungi, yeast, molds, and protozoa are the main living organisms appropriate for the mycotoxin detoxification. Enzymatic and degradation sorptions are the main mechanisms involved in microbiological detoxification of mycotoxins. Regardless of the method used, proper management tools that consist of before-harvest prevention and after-harvest detoxification are required. Here, in this review, we focus on the microbiological detoxification and mechanisms involved in the decontamination of mycotoxins.

Effect of Sodium Cromoglycate on Acetic Acid-induced Ulcerative Colitis in Mice.

Background/Aims: Ulcerative colitis (UC) is a type of inflammatory bowel disease that mainly involves the colon. Thus far, glucocorticoids and amino-salicylate have been the main treatment. Methods: To assess drugs with fewer side effects, this study evaluated the effects of sodium cromoglycate (SCG) on acetic acid-induced UC in rats. The treatment groups included SCG receivers (50 and 100 mg/kg, intra-orally) and sulfasalazine (SSZ) receivers (100 mg/kg, intra-orally). The colonic mucosal injury was assessed by clinical, macroscopic, and histopathological examinations. Results: In the treatment groups with 50 and 100 mg/kg of SCG, the clinical activity score decreased to 2.67±0.18 and 1.73±0.21 (p<0.05), respectively, compared to the UC control group (3.21±0.31), and were higher than that of the group given the standard treatment of 100 mg/kg SSZ (1.10±0.09). The treatment groups with 50 and 100 mg/kg of SCG showed a lower clinical gross lesion score than the UC control group (2.91±0.28 and 2.10±0.43, vs. 4.49±0.61, p<0.05) and were higher than the standard group (0.95±0.18). Treatment with SCG (100 mg/kg) decreased the macroscopic scores significantly compared to the UC control group (p<0.05) on the 8th day. Conclusions: SCG (100mg/kg) decreased significantly the clinical activity score, gross lesion, and percentage-affected area compared to the UC controls on the 8th day.

Celecoxib inhibits acute edema and inflammatory biomarkers through peroxisome proliferator-activated receptor-γ in rats.

OBJECTIVES: Celecoxib (CLX), a selective cyclooxygenase-II (COX-2) inhibitor, has been used for management of several inflammatory disorders. The present study aimed to explore the role of peroxisome proliferator-activated receptor-gamma (PPARγ) in CLX induced anti-inflammatory response in rats. MATERIALS AND METHODS: Carrageenan-induced paw edema was used as an acute inflammation model. Rats were treated with various intra-peritoneal (IP) doses of CLX (0.3-30 mg/kg) and pioglitazone (PGL; PPARγ agonist, 1-20 mg/kg) alone or in combination. Amounts of PPARγ, COX-2, and prostaglandin E2 (PGE2) in paw tissue, and extents of TNF-α and IL-10 in serum were measured. Moreover, levels of oxidative stress parameters as malondialdehyde (MDA), glutathione (GSH), glutathione peroxidase (GPx) activity in the cortex, hippocampus, and paw tissues were also determined. RESULTS: CLX and PGL dose-dependent administration (IP), alone or in combination reduced carrageenan-induced paw edema. Further, both agents, alone or in combination, reduced either the amounts of COX-2, PGE2, and MDA in the inflamed paw, and the levels of TNF-α in serum which were elevated by carrageenan. Both drugs also increased both levels of PPARγ, GSH, GPx activity in paws, and serum levels of IL-10 that were decreased by carrageenan. Intraplantar injection of GW-9662 (IPL), a selective PPARγ antagonist, inhibited all biochemical modifications caused by both single and combined drug treatments. CONCLUSION: CLX produced its anti-inflammatory effects probably through PPARγ receptor activation. Besides, increased anti-inflammatory effects of CLX with PGL suggest that their combination might be applied for the clinical management of inflammation especially in patients suffering from diabetes.

Tropisetron attenuates tumor growth and progression in an experimental model of mouse lung cancer.

The antineoplastic effects of 5-hydroxytryptamine (5-HT) receptor antagonists have been shown in previous studies. However, the exact underlying mechanisms mediating these antineoplastic effects are unclear. In the present study, we assessed the antineoplastic effects of tropisetron, a 5-HT receptor antagonist, in an experimental model of lung cancer in BALB/c mouse. Lewis lung carcinoma cell line was used to induce lung cancer. Mice were divided into four groups (n = 6) as follows: tumor-bearing mice + tropisetron (5 mg/kg intraperitoneally [IP]), tumor-bearing mice + tropisetron (10 mg/kg IP), tumor-bearing mice + saline, healthy mice + tropisetron (10 mg/kg). Tumor burden, interferon-γ (IFN-γ), interleukin (IL)-4, pathological response, Ki-67, and E-cadherin were assessed using enzyme-linked immunosorbent assay, and real-time polymerase chain reaction. Comet assay was used to assess DNA toxicity. Tropisetrone-treated animals (either 5 or 10 mg/kg) showed significantly lower tumor sizes at the day 24th after tumor induction. Tropisetron received animals also showed significantly higher levels of IFN-γ, E-cadherin, pathologic response, and necrotic cells compared to the saline-treated counterparts. In addition, the levels of IL-4, and Ki-67 were significantly lower in tropisetrone treated mice in comparison with control. Furthermore, tropisteron coadministration signifcantly reduced H2 O2 -induced DNA toxicity while treatment with tropisteron alone showed no adverse effect on DNA. Tropisetrone can be used as a potential antineoplastic drug in lung cancer. This agent can promote its antineoplastic effects in part through modulating inflammatory and proliferating markers.

Antimicrobial resistance, prevalence of resistance genes, and molecular characterization in intestinal Bacteroides fragilis group isolates.

Since the level of antimicrobial resistance in Bacteroides fragilis has increased, monitoring the antimicrobial susceptibility could be necessary. The objectives of this study were to (i) investigate the prevalence of species, the occurrence of reduced antimicrobial susceptibility (E-test method), and antibiotic resistance genes in the B. fragilis group and (ii) evaluate the prevalence of enterotoxigenic B. fragilis and the distribution of bft gene subtypes in hospitalized patients. As many as 475 isolates out of 250 stool samples were detected to be B. fragilis group by using conventional biochemical tests (API-32A system) and multiplex-PCR. In addition, 48.2%, 13.9%, 76.6%, and 1.2% of B. fragilis group isolates were resistant (according to EUCAST breakpoint) to piperacillin-tazobactam, meropenem, clindamycin, and metronidazole, respectively. Six metronidazole-resistant strains were isolated; B. fragilis (n: 3), B. thetaiotaomicron, B. vulgates, and B. ovatus. The presence of the cfiA, cepA, ermF, and nim genes was observed in 3.8%, 15.9%, 34.1%, and 0.7% of the B. fragilis isolates, respectively. One hundred thirty-two B. fragilis isolates (27.8%)and 21 B  fragilis isolates (15.9%) turned out to be bft gene positive by multiplex-PCR; eleven isolates (52.4%) harbored bft-1, eight isolates (38%) harbored bft-2 isotypes, and two isolates (9.5%) harbored bft-3 isotype (16.66%). These bacteria harbor antimicrobial resistance genes that could be transferred to other susceptible intestinal strains. Further investigations on lineage analysis are needed for a better understanding of these bacteria in Iran.

Fosfomycin: mechanisms and the increasing prevalence of resistance.

There are challenges regarding increased global rates of microbial resistance and the emergence of new mechanisms that result in microorganisms becoming resistant to antimicrobial drugs. Fosfomycin is a broad-spectrum bactericidal antibiotic effective against Gram-negative and certain Gram-positive bacteria, such as Staphylococci, that interfere with cell wall synthesis. During the last 40 years, fosfomycin has been evaluated in a wide range of applications and fields. Although numerous studies have been done in this area, there remains limited information regarding the prevalence of resistance. Therefore, in this review, we focus on the available data concerning the mechanisms and increasing resistance regarding fosfomycin.

Physicochemical Characteristics of Rat Muscle Glycogen Fractions.

INTRODUCTION: Homogenization of animal tissues with cold Perchloric Acid (PCA) produces two fractions of glycogen, Acid Soluble Glycogen (ASG) and Acid Insoluble Glycogen (AIG). AIM: To determine some physicochemical characteristics of muscle glycogen fractions in two groups of rat. MATERIALS AND METHODS: An experimental study was conducted on two groups of five male rats. Rats in control group were kept at rest and in case group on 30 minutes physical activity. The content of carbohydrate, protein, phosphate, index and relative Molecular Weights (MWs) were determined for glycogen fractions. RESULTS: Total glycogen decreased following muscular activity (1.40±0.08, mg/g wet muscle vs. 0.97±0.11, p<0.05) and the change occurred totally in ASG (1.02±0.07 vs. 0.57±0.07, p=0.017), whereas, AIG changed insignificantly (0.39±0.05 vs. 0.36±0.02, p=0.5). The protein content of AIG was about 5.5 times of ASG fraction. The ratio of carbohydrate to protein was 0.33±0.01 (mg/mg) in ASG and decreased to 0.19±0.02, p=0.01 after 30 minute activity. This ratio in AIG was about 6% of ASG fraction and did not change significantly during physical activity. The ratio of phosphate to protein was three times in ASG relative to AIG at rest and did not change following activity. The index of molecular weight was calculated for each fraction of glycogen as the ratio of concentration per osmolality (mg/mmol). The index was 1.82±0.02 for ASG at rest and decreased significantly to 1.07±0.12, p<0.05 following 30 minutes activity. The index did not change significantly for AIG fraction (0.56±0.05 vs. 0.48±0.10, p=0.4). The relative MW of the fractions of ASG to AIG was 3.3±0.3 at rest and decreased significantly to 2.2±0.6, p<0.05 following 30 minutes activity. CONCLUSION: Two fractions of muscle glycogen, ASG and AIG, differ in the relative carbohydrate: protein content and ASG have a higher mean of MW and is more metabolic active form.

The efficacy of low-level laser therapy for the treatment of myogenous temporomandibular joint disorder.

Low-level laser therapy (LLLT) has been commonly used for the treatment of painful musculoskeletal conditions, but the results of previous studies on this subject are controversial. The aim of this study was to evaluate the efficacy of LLLT in the management of patients with myogenic temporomandibular joint disorders (TMDs). In this randomized, double-blind clinical trial, 20 patients with myogenic TMD were randomly divided into laser and placebo groups. In the laser group, a pulsed 810-nm low-level laser (average power 50 mW, peak power 80 W, 1,500 Hz, 120 s, 6 J, and 3.4 J/cm(2) per point) was used on painful muscles three times a week for 4 weeks. In the placebo group, the treatment was the same as that in the laser group, but without energy output. The patients were evaluated before laser therapy (T1), after six sessions of laser application (T2), at the end of treatment (T3), and 1 month after the last application (T4), and the level of pain and the amount of mouth opening were measured. There was a significant increase in mouth opening and a significant reduction of pain symptoms in the laser group (p < 0.05). A similar improvement was not observed in the placebo group (p > 0.05). Between-group comparisons revealed no significant difference in pain intensity and mouth opening measurement at any of the evaluation time points (p > 0.05). LLLT can produce a significant improvement in pain level and mouth opening in patients affected with myogenic TMD.