A score for predicting colchicine resistance at the time of diagnosis in familial Mediterranean fever: data from the TURPAID registry.

OBJECTIVES: Colchicine forms the mainstay of treatment in FMF. Approximately 5-10% of FMF patients are colchicine resistant and require anti-IL-1 drugs. We aimed to compare the characteristics of colchicine-resistant and colchicine-responsive patients and to develop a score for predicting colchicine resistance at the time of FMF diagnosis. METHODS: FMF patients (0-18 years) enrolled in the Turkish Paediatric Autoinflammatory Diseases (TURPAID) registry were included. The predictive score for colchicine resistance was developed by using univariate/multivariate regression and receiver operating characteristics analyses. RESULTS: A total of 3445 FMF patients [256 (7.4%) colchicine-resistant and 3189 colchicine-responsive) were included (female:male ratio 1.02; median age at diagnosis 67.4 months). Colchicine-resistant patients had longer, more frequent attacks and were younger at symptom onset and diagnosis (P < 0.05). Fever, erysipelas-like erythema, arthralgia, arthritis, myalgia, abdominal pain, diarrhoea, chest pain, comorbidities, parental consanguinity and homozygosity/compound heterozygosity for exon 10 MEFV mutations were significantly more prevalent among colchicine-resistant than colchicine-responsive patients (P < 0.05). Multivariate logistic regression analysis in the training cohort (n = 2684) showed that age at symptom onset, attack frequency, arthritis, chest pain and having two exon 10 mutations were the strongest predictors of colchicine resistance. The score including these items had a sensitivity of 81.3% and a specificity of 49.1%. In the validation cohort (n = 671), its sensitivity was 93.5% and specificity was 53.8%. CONCLUSION: We developed a clinician-friendly and practical predictive score that could help us identify FMF patients with a greater risk of colchicine resistance and tailor disease management individually at the time of diagnosis.

Effect of Colchicine Treatment on Clinical Course in Children with PFAPA Syndrome.

INTRODUCTION: Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis syndrome (PFAPA) is the most common periodic fever condition in children. There is no consensus on treatment to prevent attacks and reduce their frequency. In this study, we aimed to evaluate the effectiveness of colchicine treatment in PFAPA syndrome. In addition, we described the demographic and clinical features of PFAPA patients. MATERIALS AND METHODS: We retrospectively analyzed 58 PFAPA patients who were started on colchicine treatment between January 2017 and January 2022. Demographic data, clinical features, laboratory tests, genetic analysis of MEditerranean FeVer (MEFV) mutations, and autoinflammatory disease activity index (AIDAI) scores of all patients were evaluated. In addition, patients were divided into two groups according to MEFV variants and compared. RESULTS: Attack frequency, duration, and AIDAI scores decreased in all patients after colchicine treatment. Duration of follow-up was 13.53±6.65 months. The median±IQR age at diagnosis was 3.2 (2-5) years. Thirty three (56.9%) patients had heterozygous mutations of MEFV. The most common MEFV variants were M694V (63.6%). There was no significant difference between the two groups in terms of colchicine responses. CONCLUSION: Colchicine treatment is effective and safe in patients with PFAPA who have frequent attacks. No association was established between the presence of heterozygous mutations of MEFV and colchicine response.

The importance of ambulatory blood pressure monitoring for diagnosing masked hypertension in patients with renal parenchymal scarring.

BACKGROUND: The most well-known and common long-term complication in children with renal parenchymal scarring (RPS) is hypertension (HT). The present study aimed to evaluate the presence of HT in children with RPS based on ambulatory blood pressure monitoring (ABPM) and to compare the patients' blood pressure (BP) to that in healthy controls matched for age, gender, and BMI. METHODS: The study included 55 patients aged < 18 years diagnosed with RPS who were followed up for ≥ 1 year and 48 healthy controls matched for age, gender, and BMI. RESULTS: Mean age in the RPS group was 12.8 ± 3.3 years, and 49.1% of the group were female. Among the RPS patients, 28 were diagnosed with HT based on ABPM, of which 18 (32.7%) had an office BP < 90th percentile for age, gender, and height; seven had an office BP between the 90-95th percentiles for age, gender, and height; and three had an office BP > 95 percentile for age, gender, and height. The difference in detection of HT based on ABPM between the two groups was significant (P = 0.00). CONCLUSIONS: Early diagnosis of HT via ABPM can help prevent development of kidney failure and cardiovascular disease in patients with RPS, significantly reducing the rates of morbidity and mortality. All children with RPS should be evaluated via ABPM, even if office BP measurements are normal. "A higher resolution version of the Graphical abstract is available as Supplementary information".

Predictors of rapidly progressive glomerulonephritis in acute poststreptococcal glomerulonephritis.

BACKGROUND: Acute post-streptococcal glomerulonephritis (APSGN) is an immune-mediated inflammatory respsonse in the kidneys caused by nephritogenic strains of group A ß-hemolytic streptococcus (GAS). The present study aimed to present a large patient cohort of APSGN patients to determine the factors that can be used for predicting the prognosis and progression to rapidly progressive glomerulonephritis (RPGN). METHODS: The study included 153 children with APSGN that were seen between January 2010 and January 2022. Inclusion criteria were age 1-18 years and follow-up of ≥ 1 years. Patients with a diagnosis that could not be clearly proven clinically or via biopsy and with prior clinical or histological evidence of underlying kidney disease or chronic kidney disease (CKD) were excluded from the study. RESULTS: Mean age was 7.36 ± 2.92 years, and 30.7% of the group was female. Among the 153 patients, 19 (12.4%) progressed to RPGN. The complement factor 3 and albumin levels were significantly low in the patients who had RPGN (P = 0.019). Inflammatory parameters, such as C-reactive protein (CRP), platelet-to-lymphocyte ratio, CRP/albumin ratio, and the erythrocyte sedimentation rate level at presentation were significantly higher in the patients with RPGN (P < 0.05). Additionally, there was a significant correlation between nephrotic range proteinuria and the course of RPGN (P = 0.024). CONCLUSIONS: We suggest the possibility that RPGN can be predicted in APSGN with clinical and laboratory findings. A higher resolution version of the Graphical abstract is available as Supplementary information.

Fracture strength and energy-dispersive spectroscopy analysis of 3-unit fixed partial dentures fabricated from different monolithic zirconia materials.

STATEMENT OF PROBLEM: Mastication forces in different regions affect the survival of multiunit posterior restorations. The fracture strength of 3-unit posterior monolithic zirconia fixed partial dentures (FPDs) and their fracture patterns require investigation. PURPOSE: The purpose of this in vitro study was to evaluate and compare the fracture strength and fracture pattern of 3-unit posterior FPDs fabricated from different monolithic zirconia materials. MATERIAL AND METHODS: Thirty 3-unit FPDs were fabricated from BruxZir, FireZr, and Upcera (n=10 per group). Energy-dispersive spectroscopy analysis was performed on 2 selected specimens from each group. All specimens were exposed to a mastication simulator for 1.2×106 cycles and then monotonically loaded to fracture at a crosshead speed of 1 mm/min. The surfaces of a selected fractured specimen were examined at magnifications of ×25 and ×500 with scanning electron microscopy. Conformity to normal distribution was evaluated with the Shapiro-Wilk test. One-way analysis of variance was used to compare the normally distributed initial crack formation load F initial (Fi) and catastrophic failure strength F maximum (Fm) means by group. Weibull statistics were calculated by using the maximum likelihood estimation method. The chi-square test was used to compare shape and scale parameters (α=.05). RESULTS: The mean Fm values were fail1878.9 N for Upcera, 2177.8 N for BruxZir, and 2229.4 N for FireZr. Upcera and BruxZir showed statistically significant differences for the Fm mean values (P=.039). The differences between the fracture type distributions according to the groups were statistically similar (P>.05). For Fi, Upcera presented the highest Weibull modulus value (2.199), FireZr had the lowest (1.594), while for Fm, BruxZir had the highest Weibull modulus value (9.267) and FireZr the lowest (6.572). CONCLUSIONS: Using the zirconia materials BruxZir, FireZr, and Upcera resulted in high Fm values after aging procedures. With all materials, the fractures were most commonly found in the connector areas in the tested FPDs.

Protracted febrile myalgia as a first and challenging manifestation of familial Mediterranean fever.

OBJECTIVES: Familial Mediterranean fever (FMF) is an auto-inflammatory disease that causes recurrent episodes of fever, abdominal pain, chest pain, and arthritis. Although FMF is well known, protracted febrile myalgia syndrome (PFMS) is a clinical condition that is rare and difficult to diagnose than other symptoms of FMF. PFMS causes fever, myalgia, and acute phase reactant elevation that lasts 2-4 weeks if corticosteroid treatment is not given. In some cases, fever may not be seen. The purpose of this report is to share our experience with PFMS patients in our clinic. METHODS: This is an observational, retrospective, single-centre study. We evaluated patients who had been diagnosed with PFMS at our paediatric rheumatology clinic. RESULTS: Protracted febrile myalgia syndrome was observed in 14 patients. Nine of the patients were female. The median age at the time of diagnosis of PFMS was 10 years. Only three patients had previously been diagnosed with FMF. Most of our patients were patients who had no previous complaint of FMF. PFMS attack was seen as the first clinical manifestation of FMF in 11 patients. Two patients who did not respond to steroid treatment improved with anakinra treatment. CONCLUSIONS: PFMS is a rare condition of FMF disease. It may be the first clinical manifestation of FMF disease. Fever may not be seen in all patients. Clinicians should be aware of this situation.

Effects of adropin on learning and memory in rats tested in the Morris water maze.

Adropin is a secreted peptide, which is composed of 43 amino acids and shows an effective role in regulating energy metabolism and insulin resistance. Motor coordination and locomotor activity were improved by adropin in the cerebellum. However, it is not known whether adropin administration has an effect on spatial learning and memory. In this study, we investigated the effect of adropin on spatial learning and memory and characterized the biochemical properties of adropin in the hippocampus. Thirty male Sprague-Dawley rats were randomly divided into two groups as control and adropin groups. The control group received 0.9% NaCl intracerebroventricular for 6 days, while the adropin groups received 1 nmol of adropin dissolved in 0.9% NaCl (for 6 days). The Morris water maze, Y maze, and object location recognition tests were performed to evaluate learning and memory. Also, the locomotor activity tests were measured to assess the motor function. The expression of Akt, phospho-Akt, CREB, phospho-CREB, Erk1/2, phospho-Erk1/2, glycogen synthase kinase 3 ß (GSK3ß), phospho-GSK3ß, brain-derived neurotrophic factor (BDNF), and N-methyl-d-aspartate receptor NR2B subunit were determined in the hippocampal tissues by using western blot. Behavior tests showed that adropin significantly increase spatial memory performance. Meanwhile, the western blot analyses revealed that the phosphorylated form of the Akt and CREB were enhanced with adropin administration in the hippocampus. Also, the expression of BDNF showed an enhancement in adropin group in comparison to the control group. In conclusion, we have shown for the first time that adropin exerts its enhancing effect on spatial memory capacity through Akt/CREB/BDNF signaling pathways.

Cesarean delivery is associated with suppressed activities of the stress axes.

Maternal pre- and post-delivery stress levels might be different for vaginal or cesarean deliveries. This study aimed to investigate the effects of type of delivery (vaginal or cesarean) and time of delivery (pre- and post-delivery) on the stress axes of the body, namely the hypothalamic-pituitary adrenal axis (HPA) and autonomic nervous system (ANS).Ninety-one pregnant women were volunteered to participate this prospective study. In these women, pre- and post-delivery HPA and ANS activities were measured noninvasively by salivary cortisol and heart rate variability (HRV), respectively. HRV was measured by 5-min electrocardiogram recording and time- and frequency-domain parameters were computed.Salivary cortisol concentration and HRV parameters were higher in women having vaginal delivery than those having cesarean delivery (p < 0.05). Cortisol levels did not differ between pre- and post-delivery (p > 0.05) but the time-domain parameters of HRV decreased post-delivery (p < 0.05). No interactions were observed between the types and times of delivery (p > 0.05).HPA and ANS axes had different activity patterns throughout the delivery process and they were higher during vaginal delivery, suggesting that they are integral parts of normal birth process and that cesarean delivery perturbs the activity of both axes.

An Assessment on the Effectiveness of the Immature Granulocyte Percentage in Predicting Internal Organ Involvement Among Children With Henoch-Schönlein Purpura.

Henoch-Schönlein purpura (HSP) is the most common childhood systemic vasculitis. The present study aims to investigate the effectiveness of the immature granulocyte (IG) percentage as a new marker for predicting internal organ involvement in HSP. This study included 75 patients below 18 years old who were diagnosed with HSP. The mean age was 7.48±2.77 years. The male/female ratio was 1.14. The findings showed that 35 (46.7%) of the patients had an internal organ involvement. The mean IG percentage was 0.88±0.68 among the patient group with HSP internal organ involvement, while it was 0.31±0.15 in the group without internal organ involvement, and a significant difference was determined between the 2 groups (P=0.000). The findings showed that the patients with renal involvement had the highest mean IG percentage (IG; 1.00±0.21). When the cutoff value for the IG percentage was specified as 0.45 to predict internal organ involvement, the sensitivity was 77.1%, and the specificity was 85%. In this study, the findings showed that IG percentage increased among patients with internal organ involvement in HSP and that its sensitivity, specificity, and predictive values were higher in predicting internal organ involvement compared with other markers.

The effect of carbamazepine, which increases oestrogen destruction, on the endometriotic implants; an experimental rat model.

We planned this experimental study to investigate the effect of carbamazepine (CMZ) on the endometriotic implants. Rats were randomised into four groups after endometriosis surgery. Drinking water was given to the sham group, 0.2 mg/kg oestradiol valerate (EV) to the EV group, 100 mg/kg/day CMZ to the CMZ group, and 0.2 mg/kg EV and 100 mg/kg/day CMZ to the EV-CMZ group. The endometrium of the rats using CMZ stained more intensely with cytochrome P450-3A4 (CYP3A4) enzyme. No endometrial hyperplasia was found in these rats. Endometriotic implants weight was found to be higher in these rats. There was no difference between the groups in terms of staining of the endometriotic implants with CYP3A4 enzyme. Endometriotic implants were less stained with the CYP3A4 enzyme than the endometrium. According to our results, CMZ does not increase the destruction of oestrogen in the endometriotic implants, unlike the endometrium. It may even cause the lesion to enlarge.Impact statementWhat is already known on this subject? Endometriosis is an oestrogen-dependent, progressive disease. Carbamazepine (CMZ) is known to increase oestrogen degradation by activating the cytochrome P450-3A4 (CYP3A4) enzyme. CMZ can be used in the treatment of endometriosis because it increases oestrogen breakdown in tissues.What do the results of this study add? CMZ can protect the endometrium against hyperplasia by increasing the amount of CYP3A4 enzyme in the endometrium. This effect could not be demonstrated in the endometriotic implants. The presence of CYP3A4 enzyme less in the endometriotic implants than in the endometrium may explain this situation. In addition, the fact that CMZ does not increase the enzyme in the endometriotic implants may contribute to this situation.What are the implications of these findings for clinical practice and/or further research? CMZ may not be a suitable alternative in the treatment of endometriosis. However, it may protect against endometrial hyperplasia. Clinical studies are needed for this effect.

An unexpected cause of chorea in an adolescent girl: systemic lupus erythematosus.

Involuntary movement disorders are rare in childhood. Hyperkinetic movement disorders including chorea stand as the leading cause. Although Sydenham chorea is the major diagnosis in most children and adolescents, appropriate differential diagnosis is fundamental for a final decision. A detailed and careful history as well as physical examination is the principal proceeding for accurate diagnosis. Herein, we report on an adolescent girl who was admitted to our hospital with chorea and subsequently diagnosed with systemic lupus erythematosus (SLE). Accompanying joint complaints in the patient's history, including growth retardation noticed during a physical examination and bicytopenia recognized in laboratory evaluation, increased the suspicion of SLE rather than Sydenham chorea in the patient. Central nervous system involvement defined as neuropsychiatric lupus presents wide clinical findings varying from stroke and seizures to psychosis and cognitive dysfunction. Although disease activity, persistently positive anticardiolipin antibodies, and lupus anticoagulant positivity are reported to be the most important risk factors in neuropsychiatric lupus, they are not always directly correlated. We present this patient in order to draw attention to the importance of physical examination and history in the differential diagnosis of chorea in childhood.

Circulating extracellular vesicles of patients with steroid-sensitive nephrotic syndrome have higher RAC1 and induce recapitulation of nephrotic syndrome phenotype in podocytes.

Since previous research suggests a role of a circulating factor in the pathogenesis of steroid-sensitive nephrotic syndrome (NS), we speculated that circulating plasma extracellular vesicles (EVs) are a candidate source of such a soluble mediator. Here, we aimed to characterize and try to delineate the effects of these EVs in vitro. Plasma EVs from 20 children with steroid-sensitive NS in relapse and remission, 10 healthy controls, and 6 disease controls were obtained by serial ultracentrifugation. Characterization of these EVs was performed by electron microscopy, flow cytometry, and Western blot analysis. Major proteins from plasma EVs were identified via mass spectrometry. Gene Ontology classification analysis and Ingenuity Pathway Analysis were performed on selectively expressed EV proteins during relapse. Immortalized human podocyte culture was used to detect the effects of EVs on podocytes. The protein content and particle number of plasma EVs were significantly increased during NS relapse. Relapse NS EVs selectively expressed proteins that involved actin cytoskeleton rearrangement. Among these, the level of RAC-GTP was significantly increased in relapse EVs compared with remission and disease control EVs. Relapse EVs were efficiently internalized by podocytes and induced significantly enhanced motility and albumin permeability. Moreover, relapse EVs induced significantly higher levels of RAC-GTP and phospho-p38 and decreased the levels of synaptopodin in podocytes. Circulating relapse EVs are biologically active molecules that carry active RAC1 as cargo and induce recapitulation of the NS phenotype in podocytes in vitro.NEW & NOTEWORTHY Up to now, the role of extracellular vesicles (EVs) in the pathogenesis of steroid-sensitive nephrotic syndrome (NS) has not been studied. Here, we found that relapse NS EVs contain significantly increased active RAC1, induce enhanced podocyte motility, and increase expression of RAC-GTP and phospho-p38 expression in vitro. These results suggest that plasma EVs are biologically active molecules in the pathogenesis of NS.

The role of autonomic pathways in peripheral apelin-induced gastrointestinal dysmotility: involvement of the circumventricular organs.

NEW FINDINGS: What is the central question of this study? Are central autonomic pathways and circumventricular organs involved in apelin-induced inhibition of gut motility? What is the main finding and its importance? Peripherally administered apelin-13 inhibits gastric and colonic motor functions through sympathetic and parasympathetic autonomic pathways, which seems to be partly mediated by the apelin receptor in circumventricular organs. ABSTRACT: Peripheral administration of apelin-13 has been shown to inhibit gastrointestinal (GI) motility, but the relevant mechanisms are incompletely understood. This study aimed to investigate (i) whether the apelin receptor (APJ) is expressed in circumventricular structures involved in autonomic functions, (ii) whether they are activated by peripherally administered apelin, (iii) the role of autonomic pathways in peripheral exogenous apelin-induced GI dysmotility, and (iv) the changes in apelin levels in the extracellular environment of the brain following its peripheral application. Ninety minutes after apelin-13 administration (300 µg kg-1 , i.p.), gastric emptying (GE) and colon transit (CT) were measured in rats that underwent parasympathectomy and/or sympathectomy. Plasma and cerebrospinal fluid (CSF) samples were also collected from another group of rats that received apelin-13 or vehicle injection. The immunoreactivities for APJ and c-Fos in circumventricular organs (CVOs) were evaluated by immunohistochemistry. Compared with vehicle-treated rats, GE and CT were inhibited significantly by apelin-13 treatment, and were completely restored in animals that underwent the combination of parasympathectomy and sympathectomy and sympathectomy alone, respectively. Apelin concentrations were elevated in both plasma and CSF following peripheral administration of apelin-13. APJ expression was detected in area postrema (AP), subfornical organ and organum vasculosum of lamina terminalis, and c-Fos expression was observed in response to apelin injection. Apelin-induced c-Fos expression in AP was partially attenuated by pretreatment with the cholecystokinin-1 receptor antagonist lorglumide, whereas it was completely abolished in vagotomized rats. The present data suggest that APJ in CVOs could indirectly contribute to the inhibitory action of peripheral apelin on GI motor functions.

A novel therapeutic approach using the Zipper method to treat chorea in a pediatric-onset systemic lupus erythematosus patient.

Pediatric-onset systemic lupus erythematosus is among the prototypic systemic autoimmune diseases seen in children. Although the neuropsychiatric involvement rate varies during the course of the disease, it is an important cause of morbidity and mortality. The clinical picture of neuropsychiatric SLE (NPSLE) is highly variable, and neurological features can precede systemic findings, leading to some diagnostic difficulties. NPSLE requires early and aggressive immunosuppressive therapy. Some patients can be resistant to immunosuppressive therapy. Chorea is a rare manifestation that occurs in 1.2%-2% of SLE patients and can result from an immunologically mediated mechanism, antiphospholipid autoantibodies or ischemia. Herein we present the first case of pediatric-onset SLE diagnosed with central nervous system involvement and treated with Zipper method. The Zipper method is a new immunomodulation treatment. The clinical findings of the patient, which were resistant to corticosteroids and cyclophosphamide, resolved by this novel treatment.

Sexual dimorphism in maternally separated rats: effects of repeated homotypic stress on gastrointestinal motor functions.

Experiencing stressful events during early life has been considered as a risk factor for development of functional gastrointestinal disorders in adulthood. This study aimed to investigate the sex-related differences in stress-induced gastrointestinal (GI) dysmotility in rats exposed to neonatal maternal separation (MS). Newborn pups were removed from mothers for 180 min from postnatal day-1 to day-14. Experiments were performed in male and female offsprings at adulthood. Elevated plus maze (EPM) test was used to assess MS-induced anxiety-like behaviors. Ninety minute of restraint stress was applied for once or 5 consecutive days for acute stress (AS) or repeated homotypic stress (RHS), respectively. Measurement of fecal output (FO) and gastric emptying (GE), and hypothalamic microdialysis were performed. Both in males and females, MS produced anxiety-like behaviors. AS delayed GE and increased FO in all groups. In RHS-loaded MS females, AS-induced alterations in GE and FO were restored, however, no adaptation was observed in male counterparts. Regardless of sex and neonatal stress experience, AS significantly increased corticotropin-releasing factor (CRF) release from paraventricular nucleus of hypothalamus, whereas females were found more susceptible than males. Following RHS, AS-induced elevations in CRF release were attenuated only in MS females, but not in males. Both females and males seem to be prone to AS-induced alterations in hypothalamic CRF system and in GI motor functions. Neonatal MS disturbs chronic stress coping mechanisms in males. Conversely, females are likely to circumvent the deleterious effects of neonatal MS on GI functions through developing a habituation to prolonged stressed conditions.

Retrospective evaluation of children with unilateral renal agenesis.

BACKGROUND: Children born with unilateral renal agenesis (URA) are thought to have a risk of developing hypertension, proteinuria, and progressive chronic kidney disease (CKD). The present study aimed to evaluate the long-term prognosis and clinical characteristics of children with URA. METHODS: The study included 171 patients aged < 18 years diagnosed as URA who were followed-up for ≥ 1 year and 121 healthy controls matched for age, gender, and BMI. RESULTS: Median age at diagnosis was 2 years (IQR: 1 month-16 years) and the incidence of URA in males (65.4%) was higher than in females. Among the patients, 21 (12.2%) had other urinary system anomalies. It was noted that 2.3% of the patients had proteinuria, 15.2% had hyperfiltration, and 2.9% had CKD. Hypertension based on ambulatory blood pressure monitoring (ABPM) was diagnosed in 18 (10.5%) of the patients, of whom 10 had masked hypertension. Diastolic blood pressure in the URA patients was significantly higher than in the healthy controls. The incidence of hypertension and CKD was significantly higher in the patients with other urinary system anomalies. CONCLUSIONS: Patients with a single functional kidney should be periodically evaluated throughout their lifetime for urine protein, blood pressure, and kidney functions. The most remarkable finding of this study is the importance of the use of ABPM for evaluating blood pressure in pediatric URA patients, especially for the detection of masked hypertension and the non-dipper phenomenon, which cannot be achieved with office blood pressure measurement.

Gastric motor dysfunction coincides with the onset of obesity in rats fed with high-fat diet.

Exposure to a high-fat diet (HFD) has been reported to impair central autonomic and enteric neurocircuitries, however, the relevant mechanisms and their time course are inadequately clarified. This study aimed to investigate the effects of HFD consumption through the period of adolescence on gastric motor functions in adulthood. Male Sprague-Dawley rats consumed a regular diet or HFD (60% kcal by fat) from 4 to 12 weeks of age. Body weight and food intake were monitored weekly. In adult rats, gastric emptying (GE) was measured. Additionally, using in-vitro organ bath, contractile and relaxant responses of antral and fundic strips were assessed with bethanechol and sodium nitroprusside (SNP), respectively. The expressions of choline acetyltransferase (ChAT), neuronal nitric oxide synthase (nNOS) and vasoactive intestinal polypeptide (VIP) were detected by immunofluorescence, whereas, the number of myenteric neurons were evaluated by staining with cuprolinic blue and enteric neuronal marker PGP 9.5. In adulthood, the HFD did not alter food intake, while significantly increasing the body weight. In HFD-fed adult rats, increased visceral fat mass was accompanied by delayed GE. Moreover, bethanechol- and SNP-induced responses were attenuated in antral and fundic tissues. HFD remarkably decreased the number of myenteric neurons and NOS immunoreactivity both in fundus and antrum. HFD remarkably decreased ChAT expression, while increasing the immunoreactivity for VIP in antrum. In conclusion, consumption of HFD between early adolescence and adulthood results in obesity and impairment of gastric motor functions. Particularly, HFD-induced gastric dysmotility appears to be predominantly dependent on the modifications in the non-adrenergic non-cholinergic inhibitory neurotransmission.

Sexual dimorphism in rats exposed to maternal high fat diet: alterations in medullary sympathetic network.

Exposure to high fat diet during perinatal period (PHFD) leads to neuroplastic changes in autonomic circuits, however, the role of gender has been incompletely understood. This study aims to investigate (i) short, and (ii) long-term effects of PHFD on autonomic outflow, and (iii) sexual dimorphic variations emerge at adulthood. Male and female rats were fed a control diet (13.5 % kcal from fat) or PHFD (60 % kcal from fat) from embryonic day-14 to postnatal day-21. To assess changes in autonomic outflow, heart rate variability (HRV) was analyzed at 10- and 20-week-old ages. Expressions of tyrosine hydroxylase (TH), metabotropic glutamate2/3 receptor (mGlu2/3R), N-methyl-D-aspartate1 receptor (NMDA1R), and gamma aminobutyric acidA receptor (GABAAR) were evaluated by immunohistochemistry. PHFD did not affect the body weight of 4-, 10-or 20-week-old male or female offsprings. PHFD significantly increased the sympathetic marker low frequency (LF) component, and sympatho-vagal balance (LF:HF) only in 10-week-old PHFD males. Compared with control, the propranolol-induced (4 mg·kg- 1, ip) decline in LF was observed more prominently in PHFD rats, however, these changes were found to be restored at the age of 20 weeks. In caudal ventrolateral medulla and nucleus tractus solitarius, expression of mGlu2/3R was downregulated in PHFD males, whereas no change was detected in NMDA1R. The number of GABAAR-expressing TH-immunoreactive cells was decreased in rostral ventrolateral medulla of PHFD males. The findings of this study suggest that exposure to maternal high-fat diet could lead to autonomic imbalance with increased sympathetic tone in the early adulthood of male offspring rats without developing obesity.

Protective mechanism of Syringic acid in an experimental model of Parkinson's disease.

6-Hydroxydopamine (6-OHDA) is a widely used chemical to model Parkinson's disease (PD) in rats. Syringic acid (SA) is a polyphenolic compound which has antioxidant and anti-inflammatory properties. The present study aimed to evaluate the neuroprotective role of SA in a rat model of 6-OHDA-induced PD. Parkinson's disease was created by injection of 6-OHDA into the medial forebrain bundle via stereotaxic surgery. Syringic acid was administered daily by oral gavage, before or after surgery. All groups were tested for locomotor activity, rotarod performance and catatony. Dopamine levels in SN were determined by an optimized multiple reaction monitoring method using ultra-fast liquid chromatography coupled with tandem mass spectrometry (MS/MS). The immunoreactivities for tyrosine hydroxylase (TH) and inducible nitric oxide synthase (iNOS) were detected by immunohistochemistry in frozen substantia nigra (SN) sections. Nitrite/nitrate levels, iNOS protein, total oxidant (TOS) and total antioxidant (TAS) status were assayed in SN tissue by standard kits. Motor dysfunction, impaired nigral dopamine release, increased iNOS expression and elevated nitrite/nitrate levels induced by 6-OHDA were significantly restored by SA treatment. Syringic acid significantly improved the loss of nigral TH-positive cells, while increasing TAS capacity and reducing TOS capacity in SN of PD rats. These data conclude that SA is a potential therapeutic agent for the treatment of 6-OHDA-induced rat model of PD. Syringic acid reduced the progression of PD via its neuroprotective, antioxidant and anti-inflammatory effects.

Clinical features in 305 patients with juvenile idiopathic arthritis: A single center Turkish Study.

BACKGROUND: Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatologic disease of childhood. The various subtypes of JIA differ in clinical features and treatments. The aim of this study was to analyze the frequency of JIA subtypes, patient demographic and clinical features, as well as the rates of macrophage activation syndrome, uveitis, and remission in Turkish JIA patients treated at a single center, and to compare the findings to those in the literature. METHODS: The files of all JIA patients treated at our pediatric rheumatology department between January 2017 and January 2019 were retrospectively reviewed. Patient demographic, clinical, and laboratory data were obtained from the patients' files and the hospital database. RESULTS: The study included 305 patients (180 females) with a mean age at onset of 7.83 ± 4.62 years. Among all the JIA subtypes, the most frequent was oligoarthritis (41.6%), followed by enthesitis-related arthritis (29.2%), rheumatoid factor (RF)-negative polyarthritis (13.4%), systemic arthritis (9.5%), RF-positive polyarthritis (2.6%), psoriatic arthritis (2.0%), and undifferentiated arthritis (1.6%). At the time of data collection, 278 patients (91.0%) were in remission, whereas 27 patients (9.0%) had active disease. Macrophage activation syndrome developed in 12 of the 29 (41.0%) systemic arthritis. Uveitis was noted in 32 (10.0%) patients. Biological agents were administered in 142 of the patients. CONCLUSIONS: The available data indicate that JIA as a whole is a heterogeneous disease with significant variability in course and long-term outcome. As such, each patient should be evaluated according to his / her disease subtype.