Direct Effect of Caffeine on Diaphragmatic Muscles in Preterm Babies Through Ultrasonographic Examination.

Caffeine is frequently used for the treatment of apnea in preterm babies. Its mechanism of action includes not only antagonism of adenosine receptors on central nervous system but also an increase in electrical activity of the diaphragm. Caffeine's direct effect on diaphragm was investigated via electromyography, but ultrasound has not been used to show visible changes in muscles after the treatment before. Therefore, we aimed to assess the effect of caffeine on diaphragmatic function through ultrasonographic examination. It was a prospective observational study. Fifty-six participants receiving nasal continuous positive airway pressure with less than or equal to 32 weeks' gestational age born were enrolled. Diaphragmatic thickness, amplitude of excursion, and velocity of movement were measured before and within 5 minutes after caffeine loading dose and compared to each other. The protocol was registered with ClinicalTrials.gov Identifier NCT04483492. Diaphragmatic thicknesses and diaphragmatic velocity of movement did not differ after the treatment. However, amplitude of excursion of the diaphragm was found significantly higher after caffeine loading dose (8.7 mm, 10mm, respectively, P < .05). Diaphragm excursion increased after caffeine treatment in preterm babies, and this finding was potentially supported the direct effect of the caffeine on diaphragm. Another important finding of this study is that it reinforces the utility of ultrasonography in assessing diaphragmatic function in preterm infants.

Further defining the molecular spectrum and long-term follow-up of 17 patients with Dyggve-Melchior-Clausen and Smith-McCort dysplasia type 2.

Dyggve-Melchior-Clausen dysplasia (DMC) and Smith-McCort dysplasia (SMC types 1 and 2) are rare spondylo-epi-metaphyseal dysplasias with identical radiological and clinical findings. DMC and SMC type 1 are allelic disorders caused by homozygous or compound heterozygous variants in DYM, while biallelic causative variants in RAB33B lead to SMC type 2. The terminology "skeletal golgipathies" has been recently used to describe these conditions, highlighting the pivotal role of these two genes in the organization and intracellular trafficking of the Golgi apparatus. In this study, we investigated 17 affected individuals (8 males, 9 females) from 10 unrelated consanguineous families, 10 diagnosed with DMC and seven with SMC type 2. The mean age at diagnosis was 9.61 ± 9.72 years, ranging from 20 months to 34 years, and the average height at diagnosis was 92.85 ± 15.50 cm. All patients exhibited variable degrees of short trunk with a barrel chest, protruding abdomen, hyperlordosis, and decreased joint mobility. A total of nine different biallelic variants were identified, with six being located in the DYM gene and the remaining three detected in RAB33B. Notably, five variants were classified as novel, four in the DYM gene and one in the RAB33B gene. This study aims to comprehensively assess clinical, radiological, and molecular findings along with the long-term follow-up findings in 17 patients with DMC and SMC type 2. Our results suggest that clinical symptoms of the disorder typically appear from infancy to early childhood. The central notches of the vertebral bodies were identified as early as 20 months and tended to become rectangular, particularly around 15 years of age. Pseudoepiphysis was observed in five patients; we believe this finding should be taken into consideration when evaluating hand radiographs in clinical assessments. Furthermore, our research contributes to an enhanced understanding of clinical and molecular aspects in these rare "skeletal golgipathies," expanding the mutational spectrum and offering insights into long-term disease outcomes.

Curcumin as a Potential Therapeutic Agent for Mitigating Carbon Monoxide Poisoning: Evidence from an Experimental Rat Study.

BACKGROUND Carbon monoxide (CO) is a poisonous gas and causes tissue damage through oxidative stress. We aimed to investigate the protective value of curcumin in CO poisoning. MATERIAL AND METHODS Twenty-four female Spraque Dawley rats were divided into 4 subgroups: controls (n=6), curcumin group (n=6), CO group (n=6), and curcumin+CO group (n=6). The experimental group was exposed to 3 L/min of CO gas at 3000 ppm. Curcumin was administered intraperitoneally at a dosage of 50 mg/kg. Hippocampal tissues were removed and separated for biochemical and immunohistochemical analysis. Tissue malondialdehyde (MDA) levels, nitric oxide (NO) levels, and superoxide dismutase (SOD) and catalase (CAT) activities were assayed spectrophotometrically, and serum asymmetric dimethylarginine (ADMA) were measured using the ELISA technique. Tissue Bcl-2 levels were detected by the immunohistochemistry method. RESULTS Tissue CAT and SOD activities and NO levels were significantly lower, and MDA and serum ADMA levels were higher in the CO group than in the control group (P<0.001). The curcumin+CO group had higher CAT activities (P=0.007) and lower MDA than the CO group (P<0.001) and higher ADMA levels than the control group (P=0.023). However, there was no significant difference observed for tissue SOD activity or NO levels between these 2 groups. In the curcumin+CO group, the Bcl-2 level was higher than that in the CO group (P=0.017). CONCLUSIONS The positive effect of curcumin on CAT activities, together with suppression of MDA levels, has shown that curcumin may have a protective effect against CO poisoning.

Preferential involvement of the pelvis and hips along with active sacroiliitis in chronic nonbacterial osteomyelitis: MRI of 97 patients from a single tertiary referral center.

OBJECTIVE: To present MRI distribution of active osteitis in a single tertiary referral center cohort of patients with chronic nonbacterial osteomyelitis (CNO). METHODS: Two musculoskeletal radiologists retrospectively reviewed MRI examinations of all patients with a final clinical diagnosis of CNO over 15 years. Sites of active osteitis at any time during the course of disease were divided into seven groups: (A) mandible, sternum, clavicles, or scapulas; (B) upper extremities; (C) subchondral sacrum and ilium immediately subjacent to sacroiliac joints (active osteitis denoting "active sacroiliitis" here); (D) pelvis and proximal 1/3 of femurs (excluding group C); (E) bones surrounding knees including distal 2/3 of femurs and 1/2 of proximal tibias and fibulas; (F) distal legs (including distal 1/2 of tibias and fibulas), ankles, or feet; (G) spine (excluding group C). Temporal changes of lesions in response to treatment (or other treatment-related changes such as pamidronate lines) were not within the scope of the study. RESULTS: Among 97 CNO patients (53 males [55%], 44 females; age at onset, mean ± SD, 8.5 ± 3.2 years; age at diagnosis, 10.3 ± 3.3 years), whole-body (WB) MRI was performed in 92%, mostly following an initial targeted MRI (94%). A total of 557 (346 targeted and 211 WB) MRIs were analyzed. Biopsy was obtained in 39 patients (40%), all consistent with CNO or featuring supporting findings. The most common locations for active osteitis were groups D (78%; 95% CI 69‒85%) and C (72%; 95% CI 62‒80%). CONCLUSION: Pelvis and hips were preferentially involved in this cohort of CNO patients along with a marked presence of active sacroiliitis. CLINICAL RELEVANCE STATEMENT: When suggestive findings of CNO are identified elsewhere in the body, the next targeted site of MRI should be the pelvis (entirely including sacroiliac joints) and hips, if whole-body MRI is not available or feasible. KEY POINTS: • Heavy reliance on MRI for diagnosis of CNO underscores the importance of suggestive distribution patterns. • Pelvis and hips are the most common (78%) sites of CNO involvement along with active sacroiliitis (72%). • Pelvis including sacroiliac joints and hips should be targeted on MRI when CNO is suspected.

The importance of skeletal x-ray screening for dysostosis multiplex in the early diagnosis of mucopolysaccharidosis.

PURPOSE: Our aim is the early detection of mucopolysaccharidosis (MPS) by examining the radiographs taken for reasons other than a metabolic disease, such as infection, trauma, and short stature. METHODS: The radiographs of children who applied to outpatient and emergency clinics in our hospital between 01/01/2022 and 31/12/2022 were examined by a pediatric radiologist retrospectively without knowledge of patient information. The MPS enzyme panel and urine glycosaminoglycan analysis were performed in patients having dysostosis multiplex on radiographs. In cases with MPS detected by enzyme and urine analysis, the definitive diagnosis was confirmed by genetic analysis. RESULTS: Skeletal radiographs of 15.104 cases admitted to our hospital were examined (11,270 chest x-ray, 314 lumbosacral spine x-ray, 2970 hand x-ray, 253 pelvis x-ray, 162 skull x-ray, and 135 complete skeletal surveys). In 67 children, dysostosis multiplex was observed in the skeletal X-ray. Among them, seven newly diagnosed MPS cases were detected. Three cases were diagnosed with MPS type 4A, two with MPS type 6, one with MPS type 2 and one with MPS type 3B. Age at diagnosis was 46.2 ± 30.6 months (range; 20-111 months). There was a history of consanguinity in 6 (85.7%) cases. CONCLUSION: Radiographs can provide clues for diagnosing MPS before the clinical findings become prominent in children admitted to the hospital for other complaints. Therefore, X-ray screening can be performed on children in endemic regions of MPS to search for dysostosis multiplex.

The effects of systemic use of nicotine on the rat nasal mucosa: a histopathologic and immunohistochemical study / Efectos del uso sistémico de nicotina sobre la mucosa nasal de la rata: un estudio histopatológico e inmunohistoquímico

The objective of this study was to evaluate the histopathologic effects of systemic use of nicotine on the rat nasal mucosa. Twelve adult Sprague-Dawley rats weighing 180-220 g, were used as experimental animals. The rats were divided into Nicotine and control groups. The rats of Nicotine groups (n=6) were administered 2mg/kg Nicotine sulphate for 28 days. The rats of control group (n=6) were only administered 1,5 ml physiologic saline solution subcutaneously for 28 days. All animals were sacrified at the end of the study and nasal tissue samples were removed and prepared for histologic examination. The sections were stained with Hematoxylin and Eosin (H-E) and Periodic acid-Schiff (PAS) and Trichrome-Masson were observed under light microscope. E-cadherin immunreactivity of pseudostrafied epithelial cells of nasal mucosa was assessed by immunohistochemical staining. There were significant differences in average histopathological score between the groups treated and non-treated to nicotine. In nicotine group, degenerative change of epithelial cells and hypertrophy of goblet cells were observed. Leukocytes infiltration was observed in significant areas of connective tissue. E-cadherin expression was significantly decreased in epithelial cells of the nasal mucosa of Nicotine group...

El objetivo de este estudio fue evaluar los efectos histopatológicos del uso sistémico de nicotina sobre la mucosa nasal de la rata. Se utilizaron como animales de experimentación 12 ratas Sprague-Dawley adultas, entre 180-220 g, divididas en grupos de nicotina y control. Al grupo de nicotina (n = 6) se le administró sulfato de nicotina 2mg/kg durante 28 días. Al grupo control (n = 6) se les administró sólo 1,5 ml de solución salina fisiológica por vía subcutánea durante 28 días. Todos los animales fueron sacrificados al final del estudio. Se tomaron muestras del tejido nasal y se examinaron histológicamente. Las secciones fueron teñidas con H-E, ácido periódico de Schiff (PAS) y tricrómico de Masson, observándose bajo microscopía de luz. Además, se evaluó la inmunoreactividad a E-cadherina de las células del epitelio pseudoestraficado de la mucosa nasal. Hubo diferencias significativas en la puntuación histopatológica media entre los grupos tratados y no tratados con nicotina. En el grupo de nicotina, se observaron cambios degenerativos de las células epiteliales e hipertrofia de las células caliciformes. Se observó una infiltración significativa de leucocitos en diferentes áreas del tejido conectivo. La E-cadherina se redujo significativamente en las células epiteliales de la mucosa nasal del grupo nicotina...

The prophylactic effects of folic acid and vitamin E against valproic acid during fetal thymus development: an ultrastructural study / Los efectos profilácticos del ácido fólico y la vitamina E contra el ácido valproico durante el desarrollo fetal del timo: un estudio ultraestructural

To evaluate histopathologic differences in the thymus of Wistar Albino rat fetuses prenatally exposed to valproic acid (VPA), folic acid (FA) and vitamin E (Vit-E). VPA (400 mg/kg), FA (400 mcg/kg) and Vit -E (250 mg/kg) were administered to rats on each of gestation days 8, 9 and 10. The fetuses (n:24) were divided into four groups: control, VPA, VPA+Vit-E and VPA+FA groups. On the 20th day of gestation, all pregnant rats were sacrificed and the fetuses were extracted. Thin sections from thymus of live fetuses were stained with uranyl acetate-lead citrate and were examined under transmission electron microscope. The histopathological findings of control group was normal. In VPA group, it showed extensive degenerative changes by VPA were on all tissue compartments when compared to controls. In VPA-FA group, vacuoles, mitochondrial cristalysis and swelling were decreased in cytoplasm. In VPA-Vit-E group, lipid storage and vacuolization were observed. Mitochondrial cristalysis decreased. Our aim in the present study is to analyze histopathological changes which may occur in a high risk experimental model after giving of VPA. In addition, protective roles of the administration of FA and Vit-E are assessed.

Se realizó este estudio para evaluar las diferencias histopatológicas en el timo de fetos de ratas Wistar Albinas expuestas prenatalmente a ácido valproico (VPA), ácido fólico (AF) y vitamina E (Vit-E). VPA (400 mg/kg), FA (400 mcg/kg) y vitamina E (250mg/kg) administradas a ratas en los días 8, 9 y 10 de gestación. Los fetos (n=24) fueron divididos en cuatro grupos: control, APV, APV + vitamina E y VPA + FA. En el día 20 de gestación, todas las ratas preñadas fueron sacrificadas y los fetos fueron extraídos. Se obtuvieron secciones delgadas del timo de los fetos y se tiñeron con citrato de uranilo - acetato de plomo, siendo examinados al microscopio electrónico de transmisión. Los hallazgos histopatológicos del grupo control fueron normales. En el grupo VPA, se observaron cambios degenerativos en todos los compartimentos de tejido en comparación con los controles. En el grupo VPA+FA, las vacuolas, cristalisis mitocondrial e inflamación se redujeron en el citoplasma. En grupo VPA + Vitamina E, se observó el almacenamiento de lípidos y vacuolización. La cristalisis mitocondrial disminuyó. El estudio permitió analizar los cambios histopatológicos que pueden ocurrir en un modelo experimental de alto riesgo después de la administración de VPA, además, las funciones de protección por la administración de AF y vitamina E.