Safety Evaluation of Natural Drugs in Chronic Skeletal Disorders: A Literature Review of Clinical Trials in the Past 20 years

Chronic skeletal disorders (CSDs), including degenerative diseases such as osteoporosis (OP) and autoimmune disorders, have become a leading cause of disability in an ageing society, with natural drugs being indispensable therapeutic options. The clinical safety evaluation (CSE) of natural drugs in CSDs has been given priority and has been intensively studied. To provide fundamental evidence for the clinical application of natural drugs in the elderly population, clinical studies of natural drugs in CSDs included in this review were selected from CNKI, Web of Science, PubMed, Science Direct and Google Scholar since 2001. Seventeen randomized controlled trials (RCTs) met our inclusion criteria: four articles were on OP, seven on osteoarthritis (OA), four on rheumatoid arthritis (RA) and two on gout. Common natural drugs used for the treatment of OP include Epimedium brevicornu Maxim [Berberidaceae], Dipsacus asper Wall ex DC [Caprifoliaceae] root, and Phalaenopsis cornu-cervi (Breda) Blume & Rchb. f[ Orchidaceae], which have been linked to several mild adverse reactions, such as skin rash, gastric dysfunction, abnormal urine, constipation and irritability. The safety of Hedera helix L [Araliaceae] extract, Boswellia serrata Roxb [Burseraceae] extract and extract from perna canaliculus was evaluated in OA and upper abdominal pain, and unstable movements were obsrerved as major side effects. Adverse events, including pneumonia, vomiting, diarrhoea and upper respiratory tract infection, were reported when RA was treated with Tripterygium wilfordii, Hook. F [Celastraceae][TwHF] polyglycosides and quercetin (Capsella bursa-pastoris (L.) Medik [Brassicaceae]). The present review aimed to summarize the CSE results of natural drugs in CSDs and could provide evidence-based information for clinicians.

A case report of Potter’s syndrome in a newborn

Introduction. Potter’s sequence is a very rare and severe syndromic complex that includes congenital kidney defects leading to oligohydramnios, lung hypoplasia and structural skeletal disorders. Clinical case presentation: observation of a boy born from the 5th pregnancy to the mother at 37 weeks. Antenatally, the fetus was found to have bilateral renal and urinary bladder agenesis, malformations of the limbs, but the parents refused to terminate the pregnancy. After birth, the child was diagnosed with Potter’s syndrome with severe hypoplasia of the lungs, which required mechanical ventilation. In 2 hours after birth, the child developed a tension pneumothorax, which was arrested by performing drainage of the pleural cavity. During the day, the patient received complex treatment in the intensive care unit, despite which, by the 2nd day of life, the death of the child occurred. Currently, there are no guidelines for the treatment of Potter syndrome with proven positive long-term outcomes.Discussion. Children with Potter syndrome do not have the same set of symptoms, but they develop a chain of events leading to a common ultimate result - decreased amount of amniotic fluid. Abnormalities leading to oligohydramnios may include severe hypoplasia, dysplasia, polycystic, obstructive uropathy or renal agenesis. In most cases, the disease occurs sporadically, but there are also forms with transmission of the disorder through successive generations: autosomal dominant or recessive inheritance of polycystic disease, hereditary renal dysplasia caused by mutations in RET, UPK3A genes and other chromosomal abnormalities.Conclusion. Potter syndrome is a set of severe syndromes manifested by abnormalities in the development of kidneys, oligohydramnios, leading to lung hypoplasia, skeletal disorders and other congenital anomalies. The severity of congenital defects included in the set depends on the time periods when oligohydramnios occurred. Despite the availability of experimental therapies, the disease is now considered to be fatal.

KAJIAN ERGONOMI SARANA PENDUKUNG PROSES BELAJAR TERHADAP KELUHAN GOTRAK MAHASISWA INSTITUSI PENDIDIKAN X

ABSTRACT Quality of learning is determined by a classroom, where a classroom must have facilities to support the learning process, at least chairs, tables, blackboards, and LCD projectors. The design of supporting facilities for the learning process that is not following ergonomic principles can cause the risk of muscle and skeletal disorders. This study aims to examine and provide an overview related to ergonomic support facilities for the learning process contained in the classrooms of Educational Institution X. the learning process is not following the principles of ergonomics and causes complaints of skeletal muscle disorders in students. Complaints of muscle disorders felt by 97.61% of students in their body parts and related to choices when they study in the classroom, it is necessary to take corrective steps by redesigning to support the existing learning process and for students to have a comfortable seat so as not to display skeletal muscle disorders. Key word: ergonomic, study posture, MSDs ABSTRAK Kualitas pembelajaran yang baik dipengaruhi oleh karakteristik ruang kelas, dimana dalam sebuah ruang kelas harus memiliki sarana pendukung proses belajar minimal kursi, meja, papan tulis, dan LCD pyoyektor. Perancangan desain sarana pendukung proses belajar yang tidak sesuai prinsip ergonomi dapat menyebabkan risiko gangguan otot dan tulang rangka Penelitian ini bertujuan untuk mengkaji dan memberi gambaran terkait ergonomic sarana pendukung proses belajar yang terdapat pada ruang kelas Institusi Pendidikan X. Berdasarkan hasil penelitian diketahui bahwa desain sarana pendukung proses belajar tidak sesuai dengan prinsip ergonomi dan menyebabkan keluhan gangguan otot rangka pada mahasiswa. Keluhan gangguan otot rangka dirasakan oleh 97,61% mahasiswa pada bagian-bagian tubuhnya dan berhubungan bermakna dengan postur janggal pada saat mereka belajar di ruang kelas diperlukan adanya langkah perbaikan dengan mendesain ulang sarana pendukung proses belajar yang ada dan atau menyerukan kepada mahasiswa agar memilih tempat duduk yang nyaman agar tidak mengeluhkan gangguan otot rangka. Kata kunci: ergonomi, postur belajar, gotrak

Zebrafish Models for Human Skeletal Disorders

In 2019, the Nosology Committee of the International Skeletal Dysplasia Society provided an updated version of the Nosology and Classification of Genetic Skeletal Disorders. This is a reference list of recognized diseases in humans and their causal genes published to help clinician diagnosis and scientific research advances. Complementary to mammalian models, zebrafish has emerged as an interesting species to evaluate chemical treatments against these human skeletal disorders. Due to its versatility and the low cost of experiments, more than 80 models are currently available. In this article, we review the state-of-art of this “aquarium to bedside” approach describing the models according to the list provided by the Nosology Committee. With this, we intend to stimulate research in the appropriate direction to efficiently meet the actual needs of clinicians under the scope of the Nosology Committee.

Genetic Study of IL6, GDF5 and PAPPA2 in Association with Developmental Dysplasia of the Hip

Background: Developmental dysplasia of the hip (DDH) is one of the most prevalent skeletal disorders. DDH is considered a pathologic condition with polygenic background, but environmental and mechanic factors significantly contribute to its multifactorial etiology. Inheritance consistent with autosomal dominant type has also been observed. Single-nucleotide polymorphisms (SNPs) in various genes mostly related to formation of connective tissue are studied for a possible association with DDH. Methods: We genotyped three SNPs, rs1800796 located in the promoter region of the IL6 gene, rs143383 located in the 5′ untranslated region (UTR) of the GDF5 gene and rs726252 located in the fifth intron of the PAPPA2 gene. The study consisted of 45 subjects with DDH and 85 controls from all regions of Slovakia. Results: Association between DDH occurrence and studied genotypes affected by aforementioned polymorphisms was confirmed in the case of rs143383 in the GDF5 gene (p = 0.047), where the T allele was over-expressed in the study group. Meanwhile, in the matter of IL6 and PAPPA2, we found no association with DDH (p = 0.363 and p = 0.478, respectively). Conclusions: These results suggest that there is an association between DDH and GDF5 polymorphisms and that the T allele is more frequently presents in patients suffering from DDH.

Acromesomelic dysplasia-Maroteaux type, nine patients with two novel NPR2 variants

Objectives Acromesomelic dysplasia, type Maroteaux, is an autosomal recessive skeletal dysplasia caused by biallelic loss of function variations of NPR2, which encodes a cartilage regulator C-type natriuretic peptide receptor B. NPR2 variations impair skeletal growth. It is a rare type of dwarfism characterized by shortening of the middle and distal segments of the limbs with spondylar dysplasia. Methods We performed detailed clinical and radiological evaluation and sequence analysis for NPR2. Results Herein, we report nine patients from eight families with two novel NPR2 pathogenic variants. Conclusions This study describes typical clinical phenotypes of Maroteaux type acromesomelic dysplasia, and enriches the variant spectrum of NPR2 by reporting one nonsense and one missense novel variant. We emphasize the importance of detailed clinical evaluation before genetic testing in diagnosing rare skeletal disorders.