Skeletal Damage Research Articles

Дифференциальная диагностика прогероидного неонатального синдрома

Aim. Аnalysis and synthesis of the literature data on the problem of differential diagnosis of neonatal progeroid syndrome. Key points. One of the rarest representatives of premature aging syndromes is neonatal progeroid syndrome (Wiedemann–Rautenstrauch syndrome). It is an ultra-orphan disease with autosomal recessive type of inheritance, associated with a mutation in the POLR3A, POLR3B, POLR3GL genes and characterized by congenital lipodystrophy and premature aging. The disease manifests from the first days of life: low body length and weight at birth, pronounced phenotypic features (pseudohydrocephaly, progeroid facial features, generalized lipodystrophy, neonatal incisors). Severe bronchopulmonary and skeletal damage is seen over the course of life, and average life expectancy ranges from 7 months to 2 years but can reach 27 years. The differential diagnosis is made with Hutchinson–Gilford syndrome (progeria), which clinical signs manifest at 1.5-2 years of age, and with Marfan-progeroid lipodystrophy, Fontaine syndrome, and Sekkel syndrome. Conclusion. Early diagnostics is necessary for predicting the course of the disease, selection of treatment, and determining of further management. Keywords: neonatal progeroid syndrome, Wiedemann–Rautenstrauch syndrome, premature aging syndromes

Use of branched-chain amino acids for reducing exercise-caused skeletal muscle damage

Introduction: Skeletal muscles damage (direct and vicarious) slows down the recovery processes in patients with injuries of the musculoskeletal system. It occurs in the early postoperative period as well. An increase in the rigidity of the skeletal muscle extracellular matrix can reduce pain, tissue swelling, and accelerate the recovery of contractility.Objective: The analyses of the effect of branched-chain amino acids (BCAAs) intake on the expression of IGF1 genes, type 1, 3 and 5 collagen, which are crucial in the composition of the skeletal muscle extracellular matrix, as well as on the muscle membrane damage against the background of chronic damage to skeletal muscles.Material and methods: 12 young healthy male subjects, skiers aged 19 (18; 22) received a placebo treatment (maltodextrin, 100 mg/kg body weight/day; n = 6) or a mixture of amino acids (leucine, isoleucine, valine – 50:25:20 mg/kg body weight/day respectively; n = 6). The treatment was received daily against the background of a large amount of aerobic high-intensity training (up to 22 hours per week). Before and after the amino acids intake a biopsy of the musculus vastus lateralis was performed, and venous blood samples were taken during the experiment.Results: The intake of leucine against the background of training led not only to a pronounced increase in the level of IGF1 protein in blood by 1.5 times (which corresponds to the literature data), but also to a trend towards an increase in the expression of IGF1Ea mRNA by 1.8 times in the skeletal muscle, and a decrease in the level of markers of muscle membranes damage – creatine phosphokinase (CPK) activity and myoglobin. In addition, changes in the IGF1-dependent collagen genes expression strongly correlated with changes in IGF1Ea expression, but not with IGF1 protein in blood (pooled group, n = 12). Thus, the intake of leucine as a part of the essential amino acids can reduce damage to skeletal muscles caused by excessive physical activity, lack of physical activity, or direct trauma.Conclusion: A 10-week BCAAs intake by individuals with documented chronic muscle membrane damage caused an increase of basal levels of IGF1 in blood and a trend towards increased IGF1Ea mRNA expression in skeletal muscle, and also caused a modest reduction in damage of skeletal muscle membrane.

BONE BIOLOGY, OSTEOIMMUNOLOGY AND RHEUMATIC DISEASES

Osteoimmunology (OI) is a relatively new field in medicine, improving our understanding of the pathogenesis of the rheumatic diseases. OI focuses on the relationship and interaction between the immune and the musculoskeletal systems, observing these processes in three main aspects: regulating the bone resorption by the immune system, the impact of inflammation on the bone formation, the role of bone and bone marrow as a depot for immune cells. Changes in the bone architecture may be due to the activation of the immune system. Proinflammatory cytokines leading in the pathogenesis ofthe inflammatory joint disease are potent activators of nuclear factor-kB receptor activator (RANKL) expression and thus promote the osteoclast differentiation. This link explains why therapy whose target are the cytokines , especially TNF inhibition, is very effective in delaying structural damage in rheumatic diseases. Knowledge of these mechanisms would allow better use of medical therapies to reduce skeletal damage.

Supplementation of Dimethylglycine Sodium Salt in Sow Milk Reverses Skeletal Muscle Redox Status Imbalance and Mitochondrial Dysfunction of Intrauterine Growth Restriction Newborns.

The current study sought to understand the mechanism underlying skeletal muscle dysfunction brought on by intrauterine growth restriction (IUGR) and to explore the treatment benefits of applying dimethylglycine sodium salt (DMG-Na) in sow milk to newborns during the suckling period. Each of the 10 sows delivered one newborn with a normal birth weight (NBW) and one with an IUGR. Additionally, two NBW and two IUGR newborns were collected per litter of another 10 sows. The 20 NBW newborns were divided between the N (sow milk) and ND (sow milk + 0.1% DMG-Na) groups, while 20 IUGR newborns were divided between the I (sow milk) and ID (sow milk + 0.1% DMG-Na) groups. The skeletal muscle histomorphology, redox status, and levels of gene and protein expression were worse (p < 0.05) in the I group than in the N group. In addition, supplementation with DMG-Na (ND and ID groups) improved (p < 0.05) those parameters compared to the unsupplemented groups (N and I groups). Inhibited nuclear factor erythroid 2-related factor 2 (Nrf2)/sirtuin 1 (SIRT1)/peroxisome proliferator-activated receptorγcoactivator-1α (PGC-1α) activity resulted in decreased redox status, skeletal muscle structural damage, skeletal muscle mitochondrial function impairment, and decreased performance in IUGR newborns. Supplementation of DMG-Na in sow milk activated the Nrf2/SIRT1/PGC-1α in IUGR newborns, thereby improving their skeletal muscle performance.

Samurai in Japan: Class System-Related Morphological Differences in Maxillofacial Regions in the Edo Period.

Previous studies have reported that compared to commoners in Japan’s Edo period, samurai had long heads, more dental irregularities, and slightly worn teeth. However, these studies did not measure the mandible or only measured length. Angular analysis is essential to evaluate the maxillofacial morphology, but there are no comparative studies of samurai and commoners. This study explored the differences in maxillofacial morphology between samurai and commoners in the Edo period. Thirty male skeletons (samurai) and thirty-eight male skeletons (commoners) were used as materials from the National Museum of Nature and Science. The selected specimens were adults aged between 20 and 59 years without serious skeletal damage and with stable occlusion of the molars. We used three-dimensional scanning to measure the specimens’ skeletal, alveolar, and facial widths. The mandibular plane angle and the gonial angle were significantly larger in the samurai than in the commoners. The ratio of the intermandibular first molars, interzygomatic arch, and mandibular width was significantly shorter in the samurai than in the commoners. The samurai had a high angle tendency and smaller mandibular width than the commoners, reflecting the class system.

Novel approaches to bone comorbidity in Cushing's disease: an update.

Skeletal complications are frequent and clinically relevant findings in Cushing's disease (CD) since an uncoupled suppressed bone formation and enhanced bone resorption leads to a marked skeletal damage with a rapid increase of fracture risk. Reduced Bone Mineral Density (BMD) has been consistently reported and osteopenia or osteoporosis are typical findings in patients with CD. Vertebral Fractures (VFs) are frequently reported and may occur even in patients with an only mild reduction of BMD, representing nowadays a still under- or misdiagnosed comorbidity of these patients being frequently asymptomatic. A novel approach combining different available tools such as BMD evaluation and vertebral morphometry, in order to improve diagnosis, management, and follow-up of bone comorbidity in all patients affected by CD, is needed. This approach is foreseen to be a crucial part of management of patients with CD, particularly in Pituitary Tumor Center of Excellence since VFs, the landmark of the bone involvement, may occur early in the history of the disease and may represent a relevant risk factor for further fractures, reduced quality of life and survival and need for pharmacologic prevention and treatment.

The Charcot Foot Reflects a Response to Injury That Is Critically Distorted by Preexisting Nerve Damage: An Imperfect Storm.

It has been recognized since comprehensive descriptions by Jean-Martin Charcot in 1868 and 1883 that development of what is usually known as neuropathic osteoarthropathy (or the Charcot foot) requires the coincidence of neuropathy and inflammation. Despite this, detailed understanding of the causes has remained remarkably limited in the succeeding century and a half. The aim of this descriptive account is to draw particular attention to the processes involved in both the onset and resolution of the inflammation that is an essential component of active disease. The principal observation is that while neuropathy is common in people with diabetes, the inflammation and secondary skeletal damage that characterize neuropathic osteoarthropathy are observed in only a small minority of people with diabetes and with neuropathy. We therefore argue that the key to understanding the causes of the Charcot foot is to focus equally on those who have active disease as well as those who do not. Although neuropathy is essential for development of the disorder, neuropathy also has an adverse impact on the mechanisms involved in the onset of inflammation, and these may be critically affected in the majority of those who are susceptible. The Charcot foot is uncommon in people with diabetes (or any other cause of neuropathy) because the large majority of those with neuropathy may have also lost the capacity to mount the specific inflammatory reaction that is essential for its development.

To Investigate the Possible Mechanism of “Asthisanghar Churna” in Asthi Bhagna W.s.r. To bone fracture: A Review Study

According to modern science Bhagna (bone fracture) is include under of Fracture. Generally, fracture take time to heal in adults 6-8 weeks, and this time of duration patient must go on bed and because of this condition may develop some complications like muscle wasting, joint stiffness, thrombosis in deep veins, improper movement of that joint etc. along these hazards patients suffers other things also like stress, irritation, and prolong healing create financial problems. It is approximate that 80% of the population faith on tradition herbal (ayurvedic) medicine which are living in developing countries. Now this modern world’s big problem and challenge is the managing of the skeletal coordination damages which come about as the consequence of trauma in maximum cases. In ancient period. Acharya Sushruta already mentioned that herbs can sufficiently effective in reducing swelling, pain and soreness of the fracture and also speedy recovery of function. Aim of this paper presents for evaluate a significant viewpoint of healing of bone breakage (bhagna) management according to the Ayurveda practice. Possession above aim in thoughts we selected “asthisanghar churna” from “Chakradutta Bhagna Chikitsa (CBC)” after which applicable keywords have been examined in diverse Ayurveda and cutting-edge writings in addition to on on-line databanks to recognize the mode of action (MOA) of character contents of Rasonadi Kalka in accelerating fractured bone recovery in instances of Bhagna (bone fracture).

Safety of Quinolones in Children: A Systematic Review and Meta-Analysis.

The results of animal experiments show that quinolone antibacterial drugs may permanently damage the soft tissues of the weight-bearing joints of young animals. Out of safety concerns, using quinolones in children has always been controversial. The aim of this study was to assess the risk of using quinolones in children and provide evidence for clinicians to support decision making. The MEDLINE (Ovid), EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), International Pharmaceutical Abstracts (Ovid), CINAHL, CNKI, VIP, and WanFang Data databases were searched from inception to 8 September 2021. All types of studies that reported the safety data of quinolones in children, including clinical trials and observational studies. Data extraction and cross-checking were completed by two independent reviewers using a pilot-tested standardized data extraction form. The overall incidence rate of adverse drug events (ADEs) in children using systemic quinolones was 5.39% and the most common ADEs were gastrointestinal reactions (incidence rate, 2.02%). Quinolone-induced musculoskeletal ADEs in children were uncommon (0.76%). Meta-analysis results showed that the risk of musculoskeletal ADEs in children using quinolones was higher than children in the control group (51 studies; rate ratio [RR] 2.03, 95% confidence interval [CI] 1.82-2.26; p<0.001; I2=18.6%; moderate-quality evidence). However, the subgroup analysis results showed that differences might only be observed in children who were followed up for 2 months to 1 year (2-6 months: RR 2.56, 95% CI 2.26-2.89; 7 months to 1 year: RR 1.35, 95% CI 0.98-1.86). Moreover, children (adolescents) aged between 13 and 18 years might be sensitive to the musculoskeletal toxicity of quinolones (RR 2.69, 95% CI 2.37-3.05; moderate-quality evidence) and the risk of levofloxacin-induced musculoskeletal ADEs might be higher (RR 1.33, 95% CI 1.00-1.77; low-quality evidence). Although the existing evidence shows that quinolone-induced musculoskeletal ADEs seem to be only short-term and reversible, and no serious skeletal and muscular system damage cases have been reported in children, quinolones should be avoided unless necessary in children because the incidence rate of quinolone-related ADEs is not low and they are broad-spectrum antibiotics that will induce the emergence of resistant strains if used frequently.

Necessity to Pay Attention to the Effects of Low Fluoride on Human Health: an Overview of Skeletal and Non-skeletal Damages in Epidemiologic Investigations and Laboratory Studies.

Due to the implementation of water improvement and fluoride reduction plans supported by central and local governments in recent years, areas with high fluoride exposure are being gradually decreased. Therefore, it is of practical importance to study the effect of low fluoride on human health. Epidemiologic investigations and in vivo and in vitro studies based on low fluoride have also confirmed that fluoride not only causes skeletal damage, such as dental fluorosis, but also causes non-skeletal damage involving the cardiovascular system, nervous system, hepatic and renal function, reproductive system, thyroid function, blood glucose homeostasis, and the immune system. This article summarizes the effects of low fluoride on human and animal skeletal and non-skeletal systems. A preliminary exploration of corresponding mechanisms that will help to fully understand the harm of low fluoride on human health was undertaken to provide the basis for establishing new water fluoride standards and help to implement individual guidance.

Water toxicants: a comprehension on their health concerns, detection, and remediation

Water is an essential moiety for the human use since a long time. Availability of good-quality water is very essential, as it is used in almost all the industrial, agricultural, and household activities. However, several factors such as increased urbanization and industrialization, extensive use of chemicals, natural weathering of rocks, and human ignorance led to incorporation of enormous toxicants into the water. The water toxicants are broadly classified as inorganic, organic, and radiological toxicants. Inorganic toxicants include heavy metals (As, Cr, Cd, Hg, Ni, Pb) and metalloids, ammonia, nitrate, and fluoride. Uranium is included in radiological toxicants which also causes chemical toxicity. Organic pollutants include polycyclic aromatic hydrocarbons, polychlorinated biphenyls, phenolic compounds, phthalate esters, pesticides, pharmaceutical and personal care products, perchlorates, and flame retardants. These toxicants are harmful for the ecosystem as well as for the human beings causing different types of health complications like lung cancer, nasal cancer, gingivitis, severe vomiting and abdominal pain, hormonal imbalance, skeletal damage, neurotoxicity like Alzheimer and Parkinson disease, renal toxicity, nephrotoxicity, etc. The USEPA and WHO specified the permissible concentration of these pollutants in the drinking water. Determination techniques having high sensitivity, low cost, rapid onsite, and real-time detection of traces of water pollutants are discussed. This review also covers in depth about the remediation techniques, for the control of water toxicants, such as chelation of the heavy metals, intoxication of pollutants using various plants, adsorption of toxicants using different sorbent medias, and photocatalytic breakdown of persistent organic pollutants (POPs).

Differential regulation of IGF‐1 pathway and accelerated bone elongation in pre‐obese juvenile mice

INTRODUCTIONChildhood obesity is driven, in large part, by increased dietary fat intake. Accelerated bone growth, a hallmark of juvenile obesity but one of its most overlooked complications, can lead to irreversible skeletal damage and chronic adult disability. Paradoxically, obese children typically have low to normal circulating levels of the growth promoting hormone insulin‐like growth factor‐1 (IGF‐1), despite their accelerated growth rate. However, IGF‐1 is both an endocrine and paracrine hormone that is essential for endochondral ossification, the process by which bones lengthen in cartilaginous growth plates at the ends of long bones. We previously reported that pre‐obese juvenile mice on a high‐fat diet have increased cell proliferation in growth plates without changes in serum IGF‐1, and before significant changes in body mass were evident. Our goal was to determine whether a high‐fat diet alters local IGF‐1 activity in growth plates by using gene set enrichment analysis on RNA sequencing (RNA‐Seq) data. We tested theHYPOTHESISthat juvenile mice on a high‐fat diet will exhibit an upregulation of IGF‐1 pathways in the growth plate.METHODSMale and female 3‐week old C57BL/6 mice were weaned on to high‐fat diet (60% kCal of fat) or control diets (10% kCal of fat) for 2 weeks and examined at 5‐weeks age when bones are elongating faster in high‐fat diet mice. We developed and validated a manual dissection technique to isolate proximal tibial growth plates from surrounding bone for RNA and protein analyses on cartilage. RNA was isolated from pooled left and right tibial growth plates and sent to the Marshall Genomics Core for next generation sequencing using an Illumina NextSeq 2000 Sequencer. Data were analyzed using fast gene set enrichment analysis (version 1.20.0) along with the reactome pathway database (version 78). Enrichment scores were calculated based on the degree to which genes in a given pathway were up‐ or down‐regulated in the RNA‐Seq data set. These scores are then normalized to account for the different number of genes involved in each pathway set and compared between diets.RESULTSOur data show that pathways regulating IGF‐1 transport and uptake by insulin‐like growth factor binding proteins (IGFBPs) were upregulated in mice on a high‐fat diet with a normalized enrichment score (NES) of 2.17 (Benjamini‐Hochberg adjusted p‐value&lt;0.01). Components of this pathway included, among others, individual IGFBPs (Igfbp4 and Igfbp5) and an IGFBP protease inhibitor (Stc2).DISCUSSIONSignificant changes in the IGF‐1 pathway closely followed those involved in cell metabolism and muscle contraction, suggesting that regulating IGF‐1 activity could be a main driver of diet‐induced growth acceleration. These data are consistent with our hypothesis that a high‐fat diet increases local IGF‐1 activity in growth plates even though systemic IGF‐1 remains unchanged.SIGNIFICANCEThese data are relevant for understanding mechanisms of diet‐induced growth acceleration and provide important groundwork for subsequent efforts to identify specific components of the IGF‐1 pathway that could underlie rapid skeletal growth in juvenile obesity.

A Comparative study between Different Treatment Modalities of Floating Knee injury At Aswan University Hospital

Purpose: The study aimed at presenting a comparison between the modalities of treatment different of floating knee injury at Aswan University Hospital. Materials and Methods: This study is a prospective study including all of our 20 cases of floating knee injuries who were treated utilizing various treatment modalities at Aswan University Hospital between December 2018 and September 2019 with a follow-up period of 12 months Results: Based on the data analysis, nailing is a better modality in floating knee injury (especially with diaphyseal long bone). Moreover, plating is a good choice for distal fractures, the external fixator is considered a choice for limb saving(as in popliteal ischemia, open fractures(OG3), and compartment syndrome). Conclusion: Management of floating knee injury is critical as floating knee injury is not like other fractures. Floating knee injuries are serious injuries with a high rate of complications. Besides being caused by high-energy trauma with extensive skeletal and soft tissue damage, they are also associated with potentially life-threatening injuries of the head, chest, and abdomen. There are multiple controversies in surgical management starting from choosing suitable fixation for each patient according to variable conditions. Floating knee injury remains a challenging orthopedic problem in which regaining good knee function outcome is a major concern. Stable osteosynthesis to achieve rigid fixation and early mobilization should always be attempted.

Effect of Salvianolate on Myocardial Ischemia Reperfusion Injury and Its Mechanism

&lt;sec&gt; &lt;title&gt;Background:&lt;/title&gt; The paper investigated the H9c2 cardiomyocyte model induced by hypoxia. Cell viability was monitored by real-time unlabeled cell function analyzer to determine the levels of LDH, MDA and SOD in cell supernatant. &lt;/sec&gt; &lt;sec&gt; &lt;title&gt;Material and Methods:&lt;/title&gt; The cytoskeleton staining was labeled by phalloidin staining. WB was applied to detect the expression of myocardial cytoskeleton microtubuleassociated protein and the expression of HIF-1α protein in each group. After adding AMPK inhibitor Compound C, Hoechst 33342 was employed to detect the apoptosis rate of cardiomyocytes, and WB was applied to detect the expressions of myocardial cytoskeleton-associated protein and p-AMPK. &lt;/sec&gt; &lt;sec&gt; &lt;title&gt;Results:&lt;/title&gt; Salvianolate can effectively improve cell viability, reduce LDH and MDA levels, increase SOD content, improve skeletal structure damage, reduce nuclear concentration, reduce cell debris, and promote the expressions of microtubule-associated protein, α-tubulin and β-tubulin, MAP4, and microfilament-associated protein MLCK, p-MLC-2 in myocardial cytoskeleton microtubules after ischemia and hypoxia. The addition of AMPK inhibitor can inhibit the expressions of p-AMPK, tubulin MAP4, microfilament protein MLCK and p-MLC-2 up-regulated by Salvianolate. &lt;/sec&gt; &lt;sec&gt; &lt;title&gt;Conclusion:&lt;/title&gt; Salvianolate can promote the expressions of microtubule-associated protein α-tubulin, β-tubulin,MAP4, microfilament-associated protein MLCK and p-MLC-2 in myocardial cytoskeleton after ischemia and hypoxia, indicating that Salvianolate can protect the myocardial cytoskeleton after ischemia and hypoxia, and may protect the structure and function of microtubules and microfilaments in the myocardial cytoskeleton through the AMPK/MAP4 and AMPK/MLCK pathways. &lt;/sec&gt;

Radiological diagnosis of multiple myeloma : Role of imaging and the current S3 guideline

Multiple myeloma is aclonal B‑lymphocyte neoplasm of terminally differentiated plasma cells and accounts for approximately 10% of all hematologic malignancies. Reduction of bone mass, seen on computed tomography (CT) as focal osteolysis, or general osteopenia is mainly caused by tumor-induced resorption of bone. Imaging methods are used in multiple myeloma to record the extent of various dimensions of the disease manifestations (damage to bone substance, bone marrow infiltration, extramedullary involvement) and the disease course. The aim of this review article is to summarize and outline the recommendations of the S3guideline "Diagnostics, therapy and follow-up care for patients with monoclonal gammopathy of unclear significance (MGUS) or multiple myeloma" in terms of radiographic imaging. The use of the conventional X‑ray skeletal status (Paris scheme) is obsolete. When apatient with symptomatic multiple myeloma is initially diagnosed, awhole-body CT should be performed to determine the extent of skeletal damage. The S3guideline also regards CT as the first imaging modality in relapse and progression.

SERUM CREATINE PHOSPHOKINASE ACTIVITY IN RABBIT DURING REGENERATION OF EXPERIMENTALLY DAMAGED MUSCLE TISSUE AND AFTER ITS STIMULATION BY TRANSPLANTED MSC

According to statistics, in modern veterinary practice, the percentage of muscle injuries among sport and working animals ranges from 40–70% of sports injuries. Quite often there are cases with muscle injuries of skeletal muscles, namely extremities. This scientific work describes the research methodology, stages of research step-by-step, and studies the relationship of dynamics of the activity of a single biochemical blood indicator. The essence of the method was to model the injury of muscle tissue performed by the skin and fascia dissection and cutting off in the area of midplane of the pelvic head of the biceps femoris muscle, measuring 1.5 x 1.5 cm to a depth of 1.5 cm of muscle tissue on 105 laboratory animals, divided into 4 groups with the use of various treatment methods. We analyze the results of one of the most effective biochemical methods for diagnosing muscle fiber of skeletal system damage and compare the activity of the enzyme creatine phosphokinase iso-enzyme depending on the stage of the study. Other research methods such as clinical, biochemical, ultrasonographic, histological research methods were recorded on 4, 7, 10, 14, 21, and 28 days. We analyzed the latest literature sources and concluded that on the 4th and 7th days, the level of creatine phosphokinase in the groups with intravenous administration, intramuscular administration of allogeneic mesenchymal stem cells is higher than the reference values but significantly lower compared to the control groups and the traditional method of treatment. But we observe a significant decrease in serum creatine phosphokinase levels in crawls on 10th day in the intravenous administration group compared to the control group of animals in 2 times, compared to traditional treatment in 1.6 times. The group of animals with intramuscular administration has reference values on the 14th day, compared with the control in 1.3 times lower, traditional treatment in 1.2 times. And on 21th day, we get reference values for a group of animals with traditional treatment. The level of creatine phosphokinase activity decreases in the control group of animals on 28th day of the research, which indicates a complete muscle rupture. The results of studies showed that the highest activity of the creatine phosphokinase enzyme during the study was shown by groups of animals with control and traditional treatment, which indicated significant structural, functional and destructive disorders of the muscle fibers of skeletal tissues with severe trauma. Thus, it is noted that the activity of the enzyme in conditions of damage of skeletal muscle tends to increase in accordance with the severity of the injury.

Study on mining of signals of adverse drug reactions of entecavir and tenofovir disoproxil based on the US FAERS database

Objective: To mine the signals of adverse drug reaction (ADR) of entecavir and tenofovir by using the US FDA Adverse Event Reporting System (FAERS) database, so as to provide reference for the safe clinical use of these two drugs. Methods: Reporting odds ratio (ROR) and proportion of report ratio (PRR) method were used to conduct data mining on the 26 quarterly reports of the US Food and Drug Administration Adverse Event Reporting System (FAERS) database between the fourth quarter of 2012 to the first quarter of 2019. The ADR descriptive terminology in the report were standardized by using the World Health Organization Adverse Reaction Terminology (System-Organ Class). ROR and PRR methods common signals were screened. Results: 104 and 187 signals of ADR of entecavir and tenofovir dipivoxil were obtained by ROR and PRR methods. The main screened system-organ classes affected by signals of ADR of entecavir were systemic damage, hepatobiliary system damage, and urinary system damage. The main screened system-organ classes affected by signals of ADR of tenofovir were urinary system damage, skeletal and musculoskeletal system damage, and metabolic and nutritional disorders. Conclusion: The mining signals of adverse drug reaction of entecavir and tenofovir dipivoxil indicate that these two drugs can cause female reproductive system damage, fetal abnormalities, neonatal and infant abnormalities, and male reproductive system damage. However, in addition to the above-mentioned ADR, the ADR instruction manual excludes entecavir and tenofovir dipivoxil primarily for respiratory and visual system damage, and the tenofovir disoproxil primarily for skin and appendage damage, and hearing and vestibular function damage. Therefore, in clinical medication management, it is suggested to pay close attention to the choice of drugs for special population infected with HBV, monitor possible ADR during medication course, and provide pharmacological monitoring to achieve personalized medication.

The possible protective effect of Panax ginseng on experimentally induced colchicine myopathy in adult male albino rats: A histological study

Myopathy is one of the side effects of colchicine, manifested as pain, dysfunction, and weakness of muscles. Ginseng extract antioxidant and anti-inflammatory activities have been reported in muscular tissue. This study was conducted to investigate whether administration of ginseng ameliorates colchicine-induced skeletal muscles damage in adult male albino rats. Forty adult male albino rats were randomly divided into four groups (ten/group) – Group I (control group): rats received normal diet and orally given normal saline, Group II: ginseng extract was administered via oral gavage daily for one month at the doses of 300 mg/kg, Group III (Colchicine treated group): rats were given colchicine (50 μg/kg/day) via oral gavage for one month, and Group IV: concomitant administration of Ginseng and colchicine for one month. Serum creatine kinase (CK) levels were measured, and skeletal muscles specimens were processed for light and electron microscopic examination. Administration of colchicine (group III) showed elevated serum CK, and histologically myofibrillar disarray foci together with cellular infiltration and edema. Group IV showed reduction in most of those manifestations. Concomitant administration of ginseng with colchicine ameliorated most of the symptoms related to colchicine induced-myopathy.

The roles of betulinic acid on circulating concentrations of creatine kinase and immunomodulation in mice infected with chloroquine-susceptible and resistant strains of Plasmodium berghei.

Complete malarial therapy depends largely on the immunological and inflammatory response of the host to the invading potentials of malarial parasite. In this study, we evaluated the roles of betulinic acid on immunological response, anti-inflammatory potentials, cardiac and skeletal muscle tissue damage in mice infected with chloroquine susceptible (NK 65) and resistant (ANKA) strains of Plasmodium berghei. Serum Interleukins 1β and 6 (IL-1β, IL-6), tumour necrosis factor alpha (TNF-α), immunoglobulins G and M (IgG and IgM), C-reactive protein (CRP) and creatine kinase (CK) were determined using ELISA technique. Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and gamma glutammyl transferase (GGT) were determined using ELISA technique. The results showed that betulinic acid decreased the levels of IL-1β, IL-6, TNF-α and CRP relative to the infected control. The IgG and IgM levels significantly increased in both models while CK did not decrease significantly in both models although serum AST, ALT and GGT significantly decreased compared to the infected control. These results showed that betulinic acid possessed anti-inflammatory, immunomodulatory and remediating effects on tissue damage. Furthermore, the decrease in activity of CK brought about by betulinic acid is indicative of decrease in cardiac and skeletal muscle injury which is a major pathological concern in Plasmodium infection and treatment.

Heterotopic ossification in mice overexpressing Bmp2 in Tie2+ lineages

Bone morphogenetic protein (Bmp) signaling is critical for organismal development and homeostasis. To elucidate Bmp2 function in the vascular/hematopoietic lineages we generated a new transgenic mouse line in which ectopic Bmp2 expression is controlled by the Tie2 promoter. Tie2CRE/+;Bmp2tg/tg mice develop aortic valve dysfunction postnatally, accompanied by pre-calcific lesion formation in valve leaflets. Remarkably, Tie2CRE/+;Bmp2tg/tg mice develop extensive soft tissue bone formation typical of acquired forms of heterotopic ossification (HO) and genetic bone disorders, such as Fibrodysplasia Ossificans Progressiva (FOP). Ectopic ossification in Tie2CRE/+;Bmp2tg/tg transgenic animals is accompanied by increased bone marrow hematopoietic, fibroblast and osteoblast precursors and circulating pro-inflammatory cells. Transplanting wild-type bone marrow hematopoietic stem cells into lethally irradiated Tie2CRE/+;Bmp2tg/tg mice significantly delays HO onset but does not prevent it. Moreover, transplanting Bmp2-transgenic bone marrow into wild-type recipients does not result in HO, but hematopoietic progenitors contribute to inflammation and ectopic bone marrow colonization rather than to endochondral ossification. Conversely, aberrant Bmp2 signaling activity is associated with fibroblast accumulation, skeletal muscle fiber damage, and expansion of a Tie2+ fibro-adipogenic precursor cell population, suggesting that ectopic bone derives from a skeletal muscle resident osteoprogenitor cell origin. Thus, Tie2CRE/+;Bmp2tg/tg mice recapitulate HO pathophysiology, and might represent a useful model to investigate therapies seeking to mitigate disorders associated with aberrant extra-skeletal bone formation.