- Changes in Thyroid Hormone Activity Disrupt Photomotor Behavior of Larval Zebrafish. [Journal Article]
- NNeurotoxicology 2019 May 20
- High throughput in vitro, in silico, and computational approaches have identified numerous environmental chemicals that interfere with thyroid hormone (TH) activity, and it is posited that human expo…
High throughput in vitro, in silico, and computational approaches have identified numerous environmental chemicals that interfere with thyroid hormone (TH) activity, and it is posited that human exposures to such chemicals is a contributing factor to neurodevelopmental disorders. However, whether hits in TH activity screens are predictive of developmental neurotoxicity (DNT) has yet to be systematically addressed. The zebrafish has been proposed as a second tier model for assessing the in vivo DNT potential of TH active chemicals. As an initial evaluation of the feasibility of this proposal, we determined whether an endpoint often used to assess DNT in larval zebrafish, specifically photomotor behavior, is altered by experimentally induced hyper- and hypothyroidism. Developmental hyperthyroidism was simulated by static waterborne exposure of zebrafish to varying concentrations (3-300 nM) of thyroxine (T4) or triiodothyronine (T3) beginning at 6 hours post-fertilization (hpf) and continuing through 5 days post-fertilization (dpf). Teratogenic effects and lethality were observed at 4 and 5 dpf in fish exposed to T4 or T3 at concentrations > 30 nM. However, as early as 3 dpf, T4 (> 3 nM) and T3 (> 10 nM) significantly increased swimming activity triggered by sudden changes from light to dark, particularly during the second dark period (Dark 2). Conversely, developmental hypothyroidism, which was induced by treatment with 6-propyl-2-thiouracil (PTU), morpholino knockdown of the TH transporter mct8, or ablation of thyroid follicles in adult females prior to spawning, generally decreased swimming activity during dark periods, although effects did vary across test days. All effects of developmental hypothyroidism on photomotor behavior occurred independent of teratogenic effects and were most robust during Dark 2. Treatment with the T4 analog, Tetrac, restored photomotor response in mct8 morphants to control levels. Collectively, these findings suggest that while the sensitivity of photomotor behavior in larval zebrafish to detect TH disruption is influenced by test parameters, this test can distinguish between TH promoting and TH blocking activity and may be useful for assessing the DNT potential of TH-active chemicals.
- Loss of function BMP4 mutation supports the implication of the BMP/TGF-β pathway in the etiology of combined pituitary hormone deficiency. [Case Reports]
- AJAm J Med Genet A 2019 May 23
- Despite BMP4 signaling being critical to Rathke's pouch induction and maintenance during early stages of pituitary development, its implication in the etiology of combined pituitary hormone deficienc…
Despite BMP4 signaling being critical to Rathke's pouch induction and maintenance during early stages of pituitary development, its implication in the etiology of combined pituitary hormone deficiency (CPHD) and other clinical presentations of congenital hypopituitarism has not yet been definitely demonstrated. We report here the first CPHD patient with a de novo pathogenic loss-of-function variant in BMP4. A 6-year-old boy, with macrocephaly, myopia/astigmatism, mild psychomotor retardation, anterior pituitary hypoplasia and ectopic posterior pituitary, clinically diagnosed with growth hormone deficiency, and central hypothyroidism, was referred for genetic analysis of CPHD. Targeted NGS analysis with a custom panel (n = 310 genes) identified a novel heterozygous de novo nonsense variant, NM_001202.5:c.794G > A, p.(Trp265*) in BMP4, which introduces a premature stop codon in the BMP4 pro-domain, impairing the transcription of the TGF-β mature peptide domain. Additional relevant variants in other genes implicated in pituitary development signaling pathways such as SMAD4 and E2F4 (BMP/TGF-pathway), ALMS1 (NOTCH-pathway), and TSHZ1 (Prokineticin-pathway), were also identified. Our results support the implication of the BMP/TGF-β signaling pathway in the etiology of CPHD and suggest that oligogenic contribution of additional inherited variants may modify the phenotypic expressivity of BMP4 pathogenic variants.
- Combined Effect of Low-Level Laser Treatment and Levothyroxine on Wound Healing in Rats With Hypothyroidism. [Journal Article]
- JLJ Lasers Med Sci 2018; 9(4):268-273
- CONCLUSIONS: Combined laser and levothyroxine treatment showed the best effect on wound healing and accelerated the closure of the wounds.
- The Combined Effects of Mesenchymal Stem Cell Conditioned Media and Low-Level Laser on Stereological and Biomechanical Parameter in Hypothyroidism Rat Model. [Journal Article]
- JLJ Lasers Med Sci 2018; 9(4):243-248
- CONCLUSIONS: The results indicated that using the LLL + CM may improve fracture regeneration and it may hasten bone healing in the hypothyroid rat.
- Safety and Efficacy of Anti-PD-1 Monoclonal Antibodies in Patients With Relapsed or Refractory Lymphoma: A Meta-Analysis of Prospective Clinic Trails. [Systematic Review]
- FPFront Pharmacol 2019; 10:387
- CONCLUSIONS: Nivolumab and pembrolizumab have promising outcomes with tolerable AEs and drug-related deaths in patients with relapsed or refractory lymphoma. Pembrolizumab caused less any grade AEs like fatigue and rash than nivolumab. Patients with HL got better response than NHL.
- Thyroid involvement in Chanarin-Dorfman syndrome in adults in the largest series of patients carrying the same founder mutation in ABHD5 gene. [Journal Article]
- OJOrphanet J Rare Dis 2019 May 22; 14(1):112
- CONCLUSIONS: Aside from the congenital ichthyosiform erythroderma, the most common symptom of CDS, in addition to other organs involvement frequently reported in the literature, we described thyroid dysfunction, an unreported feature, probably related to the lipid infiltration of the thyroid parenchyma. The association found between age and hypothyroidism in CDS patients could explain the gradually development of thyroid disease with age.We reported a thyroid dysfunction and unreported ultrasonographic aspects of kidneys and cerebral MRI in CDS patients.
- The Effects of Systemic Diseases and Medications on Implant Osseointegration: A Systematic Review. [Journal Article]
- IJInt J Oral Maxillofac Implants 2019 Suppl; 34:s35-s49
- Since their development, dental implants have become one of the most common procedures to rehabilitate patients with single missing teeth or fully edentulous jaws. As implants become more mainstream,…
Since their development, dental implants have become one of the most common procedures to rehabilitate patients with single missing teeth or fully edentulous jaws. As implants become more mainstream, determining the factors that affect osseointegration is extremely important. Medical risk factors identified to negatively affect osseointegration include diabetes and osteoporosis. However, other systemic conditions and medications that interfere with wound healing have not been as widely investigated. The aim of this systematic review was to evaluate the effect of systemic disorders including diabetes and osteoporosis on implant osseointegration. The aim was also to evaluate the effect of other diseases, such as neurocognitive diseases, cardiovascular disease, human immunodeficiency virus (HIV), hypothyroidism, rheumatoid arthritis, and medications, such as selective serotonin reuptake inhibitors (SSRIs), proton pump inhibitors (PPIs), and antihypertensives. Although the literature does not demonstrate that diabetes negatively affects implant osseointegration, most studies focus on well-controlled diabetics and the use of prophylactic antibiotics. In addition, studies have shown increased long-term bone and soft tissue complications. For osteoporosis, recent studies and reviews also fail to demonstrate a lower osseointegration rate. However, caution must be exercised in these patients due to the risk for osteonecrosis of the jaws (ONJ), especially in patients with bone malignancies. There is also no direct evidence that patients with HIV, cardiovascular disease, neurologic disorders, hypothyroidism, or rheumatoid arthritis have a decreased rate of implant osseointegration. However, some preliminary evidence suggests that medications such as SSRIs or PPIs may have a negative effect on implant osseointegration. These studies are fairly recent and must be validated with continuous research. Moreover, disease control, concomitant medications, and other comorbidities complicate implant osseointegration and must guide our treatment approaches and clinical guidelines.
- Prevalence and clinical presentation of cirrhotic cardiomyopathy: A single centre experience from southern India. [Journal Article]
- IJIndian J Gastroenterol 2019 May 21
- CONCLUSIONS: Prevalence of CCM in our setting is 33.8%. CCM is commoner in males and is independent of the etiology of cirrhosis, comorbidity and severity of liver disease. Diastolic dysfunction and prolonged QTc interval are common in CCM.
- A descriptive pilot study of mitochondrial mutations & clinical phenotype in fibromyalgia syndrome. [Journal Article]
- IJIndian J Med Res 2019; 149(1):47-50
- CONCLUSIONS: : Although the common mutation or large mtDNA deletions were not detected in blood mtDNA in the FMS patients, mutations in the muscle and sequence variation in mtDNA remained a possibility. Future studies in both blood and muscle tissue including mtDNA sequencing are warranted in such patients to determine if a subset of FMS patients have mitochondrial myopathy.
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- Novel Sodium/Iodide Symporter Compound Heterozygous Pathogenic Variants Causing Dyshormonogenic Congenital Hypothyroidism. [Journal Article]
- TThyroid 2019 May 22
- CONCLUSIONS: Sanger sequencing revealed non-previously reported compound heterozygous missense SLC5A5 gene variants (c.991G>A, p.D331N and c.1.641C>A, p.S547R). Notably, these variants have not been reported in public databases (i.e. Exome Aggregation Consortium, 1000 Genomes, and Single Nucleotide Polymorphism). In silico analysis using prediction softwares (i.e. SIFT, Polyphen-2, and MutationTaster2) support the pathologic significance of p.D331N and p.S547R NIS. Moreover, functional in vitro studies demonstrate that D331N and S547R NIS severely reduce iodide uptake when the proteins are heterologously expressed in HEK-293T cells because of a pronounced impairment of D331N and S547R NIS targeting to the plasma membrane. Of note, a charged residue at position 331 and a serine residue at position 547-which are highly conserved in SLC5A family members-are required for NIS plasma membrane targeting.We report two novel missense pathogenic variants in a compound heterozygous state in the SLC5A5 gene, detected through Sanger sequencing, in a pediatric female patient with dyshormonogenic congenital hypothyroidism.