Effectiveness of virtual reality in managing pain and anxiety in adults during periprocedural period: a systematic review and meta-analysis.

PURPOSE: Patients undergoing medical procedures often experience pain and anxiety. These periprocedural outcomes can be overcome by providing a distraction using virtual reality (VR), decreasing their perception. VR has proved effective in reducing pediatric pain and anxiety; however, limited studies have confirmed its effectiveness in adults. We performed a systematic review and meta-analysis on the effectiveness of VR, as opposed to standard care, in reducing periprocedural pain and anxiety in adults. METHODS: A systematic search of randomized controlled trials was conducted using the databases of MEDLINE, Cochrane CENTRAL, and Scopus. Trials involving patients (> 18 years) undergoing elective medical procedures conducted with or without local anesthesia and participating in VR therapy were included. Primary outcomes were pre-procedural anxiety, post-procedural anxiety, and intra-procedural pain. Pre-procedural pain, post-procedural pain, and intra-procedural anxiety were secondary outcomes. RESULTS: Data from 10 studies shortlisted for inclusion revealed no significant association between the use of VR and lower pre-procedural anxiety compared to standard care (p > 0.05) (SMD = -0.02, 95% CI = -0.18 - 0.14, P = 0.81) but demonstrated that the use of VR was significantly associated with a reduction in post-procedural anxiety (SMD = -0.73, 95% CI = -1.08 - -0.39, P < 0.0001), intra-procedural pain (SMD = -0.61, 95% CI = -1.18 - -0.04, P = 0.04), and post-procedural pain (SMD = -0.25, 95% CI = -0.44 - -0.05, P = 0.01). CONCLUSION: The use of VR caused a significant reduction in post-procedural anxiety, intra-procedural pain, and post-procedural pain in adults undergoing medical procedures, although the findings were insignificant concerning pre-procedural anxiety.

Impact of FLT3-ITD Insertion Length on Outcomes in Acute Myeloid Leukemia: A Propensity Score-Adjusted Cohort Study.

The prognostic significance of the length of internal tandem duplication (ITD) insertions in mutant FLT3 genes in acute myeloid leukemia (AML) is controversial. We conducted a retrospective study to evaluate the correlation between the ITD base-pair (bp) insertion length and clinical outcomes. The mutational status of the FLT3 gene was evaluated in 402 of 467 consecutive AML patients treated at the University of Maryland Greenebaum Comprehensive Cancer Center between 2013 and 2020; 77 had FLT3-ITD mutations. Patients were divided into three cohorts based on bp insertion length (<30 (0−33rd percentile), 30−53 (34th−66th percentile),and >53 (>66th percentile)). The median overall survival (OS) of patients was 16.5 months (confidence interval (CI) 7.3-NA), 18.5 months (CI 7.3-NA), and 21.9 months (CI 19.1-NA) (p = 0.03) for the <30, 30−53, and >53 bp insertion length cohorts, respectively. The adjusted median event-free survival (EFS) for the ITD insertion lengths >30, 30−53, and >53 bp was 11.1 months (CI 2.8−16.5), 5.2 months (CI 2.9−12.6), and 9.1 months (CI 5.4-NA) (p = 0.5), respectively. Complete remission (CR) rates were 64% (<30 inserted bp), 55% (30−53 inserted bp), and 79% (>53 inserted bp) (p = 0.23). For patients treated with gilteritinib and midostaurin, the unadjusted median OS was not statistically significantly different between cohorts.

Impact of IDH1 c.315C>T SNP on Outcomes in Acute Myeloid Leukemia: A Propensity Score-Adjusted Cohort Study.

Acute myeloid leukemia (AML) is the common type of acute leukemia in adults. Definitive prognostic significance of variants of unknown significance lacks for many commonly mutated genes, including the isocitrate dehydrogenase 1 (IDH1) synonymous single nucleotide polymorphism (SNP) variant c.315C>T. In this retrospective cohort study of 248 AML patients at the University of Maryland Greenebaum Comprehensive Cancer Center, we show that the IDH1 c.315C>T SNP, previously reported to be associated with poor prognosis by other studies with conflicting data, does not confer worse prognosis, with a median overall survival (OS) of 17.1 months compared to 15.1 months for patients without this SNP (P=0.57). The lack of negative effect on prognosis by IDH1 SNP c.315C>T is consistent with the absence of amino acid alteration (p.Gly105Gly).

Pain perception during injection of local anesthesia in pedodontics.

OBJECTIVE: Few studies have examined pain levels for the injection of local anesthesia in children, though it is a routine technique in pediatric dentistry. The objective of the study was to evaluate the difference in the assessment of procedural pain by the child, parent, dental practitioner, and independent observers during injection of local anesthesia for dental treatment in pediatric dentistry. METHOD AND MATERIALS: In total, 27 male and 22 female children (5 to 17 years of age, mean ± SD 9.8 ± 4.0 years) received local anesthesia (LA) via infiltration or mandibular alveolar blocks according to a standard protocol. After the dental treatment, the children assessed the pain levels for the procedures on a visual analog scale (VAS), while their parents and the dental practitioner used a numeric rating scale (0 to 10). Independent observers also assessed pain via video tape for an evaluation after blinding. The heart rate was monitored continuously during the procedure. The Bland-Altman method was used to quantify the comparison between pain ratings. RESULTS: The assessed level of pain by dental practitioner, parent, and child during injection of LA differed clearly (child: 3.94 ± 2.71; parent: 3.31 ± 2.60; dental practitioner: 3.02 ± 1.98; video observer 1: 1.76 ± 2.56; video observer 2: 1.89 ± 2.55). In 42.9% of cases the dental practitioner's rating and the self--reported pain by the child during injection of LA differed by ≥ 2 on the numeric rating scale, which is clinically a highly different and relevant assessment. CONCLUSION: As pain perception in children during the injection of local anesthetic and its assessment varies considerably depending on the assessing person and the treated child, dental practitioners and researchers should be cautious in interpreting the patient's pain perception.

Comparison of Three Manual Therapy Techniques as Trigger Point Therapy for Chronic Nonspecific Low Back Pain: A Randomized Controlled Pilot Trial.

Objectives: This pilot study aimed to compare the efficacy of manual pressure release (MPR), strain counterstrain (SCS), and integrated neuromuscular inhibition technique (INIT) in the management of chronic nonspecific low back pain (LBP). Design: Single-blind, randomized, controlled pilot trial. Setting: Neurosurgery clinic. Subjects: Forty-eight patients (46 women; mean age, 35.47 ± 10.58 years) diagnosed chronic nonspecific LBP and who had at least one active myofascial trigger point (MTrP) in the quadratus lumborum, iliocostalis lumborum, gluteus maximus, gluteus medius, and gluteus minimus muscles were included. Interventions: Patients received a standard home exercise program in addition to the MPR technique (MPR group), SCS technique (SCS group), and INIT (INIT group) for 12 sessions (2 days/week for 6 weeks). Outcome measures: The primary outcome was the visual analog scale (VAS). The secondary outcomes were MTrP examination, pressure pain threshold, lumbar active range of motion, Oswestry Disability Index (ODI), Beck depression inventory, and state-trait anxiety inventory. Results: There is no significant difference in terms of the percentage of deactivated MTrPs after 1st session and 12th session between groups (p > 0.05), but the percentage of deactivated MTrPs was less in MPR group than other groups. The overall group-by-time interaction for the repeated measures analysis of variance was not significant for primary and secondary outcomes (p > 0.05), but the improvement in the VAS-activity and the ODI was slightly better in the SCS group compared with other groups. Conclusions: These preliminary findings, which might help provide a glimpse into the clinical effectiveness of three manual therapy techniques (MPR, SCS, and INIT) rather than statistical significance, indicated that SCS or INIT might provide slightly better improvement in pain during activity, deactivation of MTrPs, and disability related to pain in chronic nonspecific LBP.

Potential Uses of Isolated Toxin Peptides in Neuropathic Pain Relief: A Literature Review.

Neuropathic pain is a subset of chronic pain that is caused by neurons that are damaged or firing aberrantly in the peripheral or central nervous systems. The treatment guidelines for neuropathic pain include antidepressants, calcium channel α2 delta ligands, topical therapy, and opioids as a second-line option. Pharmacotherapy has not been effective in the treatment of neuropathic pain except in the treatment of trigeminal neuralgia with carbamazepine. The inability to properly treat neuropathic pain causes frustration in both the patients and their treating physicians. Venoms, which are classically believed to be causes of pain and death, have peptide components that have been implicated in pain relief. Although some venoms are efficacious and have shown benefits in patients, their side-effect profile precludes their more widespread use. This review identifies and explores the use of venoms in neuropathic pain relief. This treatment can open doors to potential therapeutic targets. We believe that further research into the mechanisms of action of these receptors as well as their functions in nature will provide alternative therapies as well as a window into how they affect neuropathic pain.

Application of HPLC-DAD for the quantification of Lycorine in Galanthus elwesii Hook

ABSTRACT In the present study, a reversed-phase high-performance liquid chromatographic method has been used for the quantitative determination of lycorine in the aerial parts and bulbs of G. elwesii Hook. A simple method for the extraction of lycorine in low mass plant samples was employed utilizing pre-packed columns with diatomaceous earth (Extrelut(r)). The chromatographic separation was performed using an isocratic system with a mobile phase of trifluoroacetic acid-water-acetonitrile (0.01:92.5:7.5, v/v/v) applied at a flow rate 1 mL min-1 using diode array detector. The content of lycorine in the bulbs and aerial parts of G. elwesii collected from Demirci (Manisa) was found as 0.130 and 0.162 %, respectively. Additionally, in the bulbs of the specimens collected from Sogucak (Balikesir), lycorine was quantified as 0.055 %, whereas in the aerial parts, it was determined as 0.006 %. The method was validated partially with respect to system specificity, linearity, accuracy, precision, limits of detection (LOD) and quantitation (LOQ). Validation procedures displayed that the method was specific, accurate and precise.

Effect of parenterally L-arginine supplementation on the respiratory distress syndrome in preterm newborns.

L-Arginine (L-Arg) is the precursor of nitric oxide which plays an important role on pulmonary circulation and pulmonary vascular tone. Earlier studies suggested that L-Arg levels in preterm newborns with respiratory distress syndrome (RDS) were low due to its consumption and L-Arg supplementation may reduce the severity of RDS. Our aim was detect the effect of the parenterally L-Arg supplementation on RDS severity. The subjects were chosen between preterm newborns (gestational age <34 weeks) (n = 30). Twenty of the subjects were diagnosed with permaturity and RDS, and 10 of the subjects were healthy preterm newborns. Ten of the subjects was taken L-Arg (1.5 mmol/kg/d) in addition to routine RDS treatment and assumed as "Group 1". In this group, daily L-Arg supplementation was started end of the first day, and continued at end of fifth day. The others of the subjects diagnosed with RDS was take routine RDS treatment and assumed as "Group 2". Healthy preterm newborns assumed as "Group 3". Blood collections for L-Arg levels via tandem mass spectrometry were made in first day and repeated on the seventh days. Oxygenation index was used to determine severity of RDS. L-Arg consentrations in Group 1 were 8.7 ± 4.1 µM/L and 11.9 ± 5.0 µM/L in first and seventh day, respectively. L-Arg consentrations were 12.6 ± 4.5 µM/Land 10.9 ± 5.4 µM/L in Group 2 and 8.6 ± 5.1 µM/L and 9.4 ± 4.1 µM/L in Group 3. There is no correlation between L-Arg concentrations and OI also duration of the mechanical ventilation of the subjects in patient groups (Group 1 and 2).

Extract of Woodfordia fruticosa flowers ameliorates hyperglycemia, oxidative stress and improves ß-cell function in streptozotocin-nicotinamide induced diabetic rats.

ETHNOPHARMACOLOGICAL RELEVANCE: The art of Ayurveda and the traditional healing system in India have reflected the ethnomedicinal importance of the plant Woodfordia fruticosa Kurtz, which demonstrates its vast usage in the Ayurvedic preparations as well as in the management of diabetes by the traditional healers. AIMS OF STUDY: The study aimed to ascertain the antidiabetic potential of W. fruticosa flower methanolic extract (WF) on Streptozotocin (STZ)-nicotinamide-induced diabetic rat model. MATERIALS AND METHODS: Diabetes was induced in Sprague Dawley (SD) rats by STZ-nicotinamide and thereafter diabetic rats were treated with three different doses of WF (100, 200 and 400mg/kg body weight) respectively and glibenclamide as a positive control. Biochemical parameters such as blood glucose, serum insulin and C-peptide levels were measured with oxidative stress markers. Furthermore, histology of liver and pancreas was carried out to evaluate glycogen content and ß-cell structures. Moreover, immunohistochemistry and western blot analysis were performed on kidney and pancreas tissues to determine renal Bcl-2, pancreatic insulin and glucose transporter (GLUT-2, 4) protein expression in all the experimental groups. RESULTS: The acute toxicity study showed non-toxic nature of all the three doses of WF. Further, studies on diabetic rats exhibited anti-hyperglycemic effects by upregulating serum insulin and C-peptide levels. Similarly, WF shown to ameliorate oxidative stress by downregulating LPO levels and augmenting the antioxidant enzyme (ABTS). Furthermore, histopathological analysis demonstrate recovery in the structural degeneration of ß-cells mass of pancreas tissue with increase in the liver glycogen content of the diabetic rats. Interestingly, protective nature of the extract was further revealed by the immunohistochemical study result which displayed upregulation in the insulin and renal Bcl-2 expression, the anti apoptosis protein. Moreover, western blot result have shown slight alteration in the GLUT-2 and GLUT-4 protein expression with the highest dose of WFc treatment, that might have stimulated glucose uptake in the pancreas and played an important role in attenuating the blood glucose levels. CONCLUSION: The overall study result have demonstrated the potential of WF in the management of diabetes and its related complications, thus warrants further investigation on its major compounds with in depth mechanistic studies at molecular level.

Investigation on malondialdehyde, S100B, and advanced oxidation protein product levels in significant hyperbilirubinemia and the effect of intensive phototherapy on these parameters.

BACKGROUND: The parameters of oxidative stress [advanced oxidation protein products (AOPPs), malondialdehyde (MDA), and S100B] and the effect of intensive phototherapy (PT) on these parameters have not been studied extensively in newborns with significant hyperbilirubinemia (SH). We aimed to measure the levels of MDA, S100B, and AOPPs in newborns with SH, and to compare newborns with healthy control newborns without hyperbilirubinemia on the basis of these parameters of oxidative stress. In addition, we investigated the effect of intensive PT on these parameters during the treatment of SH and report our findings for the first time in the literature. METHODS: The study was performed in newborns (n = 62) who underwent intensive PT because of SH. Newborns without jaundice constituted the control group (n = 30). Both groups were compared with respect to demographic characteristics and biochemical (laboratory) parameters including MDA, AOPPs, and S100B. MDA, AOPPs, and S100B were also compared before and after intensive PT in the PT group. In the study group, a correlation analysis of demographic characteristics; MDA, AOPP, and S100B values; and changes occurring in MDA, AOPPs, and S100B values due to the effect of intensive PT was performed. RESULTS: Serum total bilirubin, S100B, and MDA levels in the PT group before performing PT were significantly higher than those in the control group. In newborns receiving PT serum total bilirubin, MDA and AOPP levels decreased significantly after intensive PT. In correlation analysis, a statistically significant negative correlation was found only between the amount of bilirubin decrease with PT and AOPP levels after PT in the study group. CONCLUSION: Whether the significant decrease in MDA levels, which was higher prior to PT, is due to the decrease in serum bilirubin levels or due to the effect of intensive PT itself remains to be determined in further studies. The decrease in AOPP levels after PT implies that intensive PT has protective effects on oxidative stress.

Quantititative determination of lycorine and galanthamine in Galanthus trojanus and G. cilicicus by HPLC-DAD.

Lycorine and galanthamine have various biological activities. A reliable HPLC method coupled with DAD detection was developed and validated for the determination of galanthamine and lycorine in Galanthus trojanus and G. cilicicus. A simple method for the extraction of the alkaloids in low-mass plant samples was employed utilizing columns pre-packed with diatomaceous earth (Extrelut). This method was applied to the aerial parts and bulbs of G. trojanus and G. cilicicus (Amaryllidaceae) collected during the flowering season. The chromatographic separation was performed using an isocratic system with a mobile phase of trifluoroacetic acid-water-acetonitrile (0.01:92.5:7.5) applied at a flow rate of 1 mL min(-1) and using a diode array detector. Validation procedures showed that the method was specific, accurate and precise. The highest amount of lycorine (0.012%) was detected in the bulbs of G. trojanus collected from Can (Canakkale), whereas the aerial parts of this species collected from Bayramiç (Canakkale) was not found to contain this alkaloid. In G. cilicicus samples, lycorine was only determined in the bulbs, giving yields of 0.004%; galanthamine yields were between 0.015-0.016%, but none of the G. trojanus samples contained this latter alkaloid.

GC-MS investigation of Amaryllidaceae alkaloids in Galanthus xvalentinei nothosubsp. subplicatus.

A GC-MS analysis of alkaloids in the aerial parts and bulbs of Galanthus xvalentinei nothosubsp. subplicatus was performed for the first time. Totally, twenty-six alkaloids were identified, of which tazettine and galanthindole were the major ones. Acetylcholinesterase inhibitory activity of the alkaloidal extracts was determined using modified in vitro Ellman's method. Significant anticholinesterase activity was observed in the tested samples (bulbs: IC50 = 21.3 microg/mL, aerial parts: IC50 = 16.3 microg/mL).

Iodine deficiency: a probable cause of neural tube defect.

INTRODUCTION: Iodine deficiency is the most devastating event in developing brain in the fetus and neonate. Iodine is absolutely necessary on the myelination, neuronal differentiation, and formation of neural processes, synaptogenesis, and neuronal migration by thyroidal hormones throughout pregnancy and shortly after birth. Neural tube defects (NTD) form after third and fourth gestational weeks and their etiologies are multifactorial. CASE REPORT: We herein present a male newborn with iodine deficiency and thoracic neuroenteric cyst bound to a myelomeningocele via a pedinculi. We hypothesize that iodine deficiency may be a cause of NTD, and iodine supplementation in preconception and pregnancy may prevent NTD.

Guaiazulene: a new treatment option for recalcitrant diaper dermatitis in NICU patients.

AIM: Based on a maternal observation, we aimed to evaluate the treatment effectiveness of guaiazulene (GA) containing local pomade in the high-risk neonates with recalcitrant diaper dermatitis (RDD). METHODS: We included 30 NICU patients of RDD, with level II-III aged between 22 and 67 days. Study group patients (n = 20) were treated with GA containing local pomade (0.05 g/100 g). Control group consisted of patients who had extended antifungal treatment. A visual scale was used to assess the response to treatment at the end of a week. Scoring was done at the beginning of the treatment, on the first, third and seventh days. RESULTS: Statistically significant differences in visual scores were determined between the two groups at the initial and following days of the treatment. In study group, improvements at the first and third days of the treatment were better than those of control group. Additionally, complete recovery rate in study group was better than that in controls. CONCLUSION: Having beneficial but no adverse effects, GA containing local pomade provided rapid recovery in risky neonates with RDD, who required rapid improvement.

Anti-diabetic effects of Centratherum anthelminticum seeds methanolic fraction on pancreatic cells, ß-TC6 and its alleviating role in type 2 diabetic rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Seeds of Centratherum anthelminticum (Asteraceae) have been popularly used in Ayurvedic medicine to treat diabetes and skin disorders. Folk medicine from Rayalaseema (Andhra Pradesh, India) reported wide spread usage in diabetes. AIM OF THE STUDY: To investigate the hypoglycemic properties and mechanism of the methanolic fraction of C. anthelminticum seeds (CAMFs) on mouse ß-TC6 pancreatic cell line and streptozotocin (STZ)-induced diabetic rat models. MATERIALS AND METHODS: We investigated the crude methanolic fraction of C. anthelminticum seeds (CAMFs) on ß-TC6 cell line and confirmed its effects on type 1 and type 2 diabetic rats to understand its mechanism in managing diabetes mellitus. CAMFs were initially tested on ß-TC6 cells for cytotoxicity, 2-NBDG glucose uptake, insulin secretion and glucose transporter (GLUT-1, 2 and 4) protein expression. Furthermore, streptozotocin (STZ)-induced type 1 diabetic and STZ-nicotinamide-induced type 2 diabetic rats were intraperitoneally (i.p) injected or administered orally with CAMFs daily for 28 days. The effect of CAMFs on blood glucose and insulin levels was subsequently evaluated. RESULTS: In cell line studies, CAMFs showed non-cytotoxic effect on ß-TC6 cell proliferation compared to untreated control cells at 50 µg/ml. CAMFs increased glucose uptake and insulin secretion dose-dependently by up-regulating GLUT-2 and GLUT-4 expression in these cells. Further in vivo studies on streptozotocin induced diabetic rat models revealed that CAMFs significantly reduced hyperglycemia by augmenting insulin secretion in type 2 diabetic rats. However, CAMFs displayed less significant effects on type 1 diabetic rats. CONCLUSIONS: CAMFs demonstrated anti-diabetic potential on ß-TC6 cells and type 2 diabetic rat model, plausibly through enhancing glucose uptake and insulin secretion.

The methanolic fraction of Centratherum anthelminticum seed downregulates pro-inflammatory cytokines, oxidative stress, and hyperglycemia in STZ-nicotinamide-induced type 2 diabetic rats.

This study aimed to ascertain the potential of Centratherum anthelminticum seeds methanolic fraction (CAMFs) for the management of type 2 diabetes and its associated complications. CAMFs was initially tested on ß-TC6 cells for H(2)O(2)-induced nuclear factor-κB (NF-κB) translocation effects. The result displayed that CAMFs significantly inhibited NF-κB translocation from cytoplasm into the nucleus, dose-dependently. Furthermore, a 12-week sub-chronic CAMFs study was carried out on streptozotocin (STZ)-nicotinamide-induced type 2 diabetic rat model to evaluate glycemia, essential biochemical parameters, lipid levels, oxidative stress markers, and pro-inflammatory cytokines level. Our study result showed that CAMFs reduced hyperglycemia by increasing serum insulin, C-peptide, total protein, and albumin levels, significantly. Whereas, elevated blood glucose, glycated hemoglobin, lipids and enzyme activities were restored to near normal. CAMFs confirmed antioxidant potential by elevating glutathione (GSH) and reducing malondialdehyde (MDA) levels in diabetic rats. Interestingly, CAMFs down-regulated elevated tumor necrosis factor α (TNF-α), interleukin (IL)-1ß and IL-6 in the tissues and serum of the diabetic rats. We conclude that CAMFs exerted apparent antidiabetic effects and demonstrated as a valuable candidate nutraceutical for insulin-resistant type 2 diabetes and its associated complications such as dyslipidemia, oxidative stress, and inflammation.

Chloroform Fraction of Centratherum anthelminticum (L.) Seed Inhibits Tumor Necrosis Factor Alpha and Exhibits Pleotropic Bioactivities: Inhibitory Role in Human Tumor Cells.

We investigated the antioxidant potential, cytotoxic effect, and TNF-α inhibition activity with NF-κB activation response in a chloroform fraction of Centratherum anthelminticum seeds (CACF). The antioxidant property of CACF was evaluated with DPPH, ORAC, and FRAP assays, which demonstrated significant antioxidant activity. The cytotoxicity of CACF was tested using the MTT assay; CACF effective inhibitory concentrations (IC(50)) for A549, PC-3, MCF-7, and WRL-68 cells were 31.42 ± 5.4, 22.61 ± 1.7, 8.1 ± 0.9, and 54.93 ± 8.3 µg/mL, respectively. CACF effectively and dose-dependently inhibited TNF-α release, in vitro and in vivo. CACF inhibited TNF-α secretion in stimulated RAW264.7 macrophage supernatants with an IC(50) of 0.012 µg/mL, without affecting their viability; the highest dose tested reduced serum TNF-α by 61%. Acute toxicity testing in rats revealed that CACF was non-toxic at all doses tested. Matching the cytotoxic activity towards a mechanistic approach, CACF dose-dependently exhibited in vitro inhibitory effects against the activation of NF-κB translocation in MCF-7 cells. Preliminary phytochemical screening with GC/MS analysis detected 22 compounds in CACF, of which morpholinoethyl isothiocyanate was the most abundant (29.04%). The study reveals the potential of CACF in the treatment of breast cancer and in oxidative stress conditions with associated inflammatory responses.

A novel mutation in the MC2R gene causing familial glucocorticoid deficiency type 1.

Familial glucocorticoid deficiency (FGD) or hereditary unresponsiveness to adrenocorticotropin (ACTH) is an autosomal recessive disorder characterized by isolated glucocorticoid deficiency associated with normal mineralocorticoid secretion. Mutations in genes encoding either ACTH receptor or melanocortin 2 receptor accessory protein are responsible for the disease in about 50% of cases, named FGD type 1 and type 2, respectively. Patients may present with hyperpigmentation, recurrent infections, failure to thrive, hypoglycemic seizures, and coma in infancy or early childhood. Here we report the case of a 17-day-old newborn diagnosed with FGD type 1 who presented with hyperbilirubinemia and hyperpigmentation, a sign which was erroneously assumed to be due to prolonged phototherapy by the referring physician. Hormone analysis showed low cortisol and high ACTH levels with normal serum electrolytes and renin-aldosterone axis. Genetic analysis revealed a novel homozygous melanocortin 2 receptor mutation p.Leu225Arg in the patient. The healthy parents were heterozygous for the mutation.

Does early treatment prevent deafness in thiamine-responsive megaloblastic anaemia syndrome?

Thiamine-responsive megaloblastic anaemia (TRMA; OMIM 249270) syndrome is an autosomal recessive disorder characterized by diabetes mellitus, megaloblastic anaemia, and sensorineural deafness. Progressive hearing loss is one of the cardinal findings of the syndrome and is known to be irreversible. Whether the deafness in TRMA syndrome can be prevented is not yet known. Here, we report a four-month-old female infant diagnosed with TRMA syndrome at an early age. There was no hearing loss at the time of diagnosis. The patient's initial auditory evoked brainstem response measurements were normal. Although she was given thiamine supplementation regularly following the diagnosis, the patient developed moderate sensorineural hearing loss at 20 months of age, indicating that early diagnosis and treatment with oral thiamine (100 mg/day) could not prevent deafness in TRMA syndrome. It would be premature to draw general conclusions from one case, but we believe that further patient-based observations can shed light on the pathophysiology of this rare syndrome as well as prediction of its prognosis.

In vitro and in vivo anti-inflammatory activity of 17-O-acetylacuminolide through the inhibition of cytokines, NF-κB translocation and IKKß activity.

BACKGROUND AND PURPOSE: 17-O-acetylacuminolide (AA), a diterpenoid labdane, was isolated for the first time from the plant species Neouvaria foetida. The anti-inflammatory effects of this compound were studied both in vitro and in vivo. EXPERIMENTAL APPROACH: Plant extracts were initially tested against LPS-stimulated release of tumor necrosis factor alpha (TNF-α) from murine macrophages (RAW264.7 cells). Based on bioassay-guided fractionation, the active compound was identified as AA. AA was tested for its ability to reduce nitric oxide (NO) production, and the inducible nitric oxide synthase (iNOS) expression. The inhibition of a panel of inflammatory cytokines (TNF, IL-1ß, IL-6, KC, and GM-CSF) by AA was assessed at the expression and the mRNA levels. Moreover, the effect of AA on the translocation of the transcription factor nuclear factor kappa B (NF-κB) was evaluated in LPS-stimulated RAW264.7 cells and in TNF-stimulated L929 cells. Subsequently, AA was tested in the inhibitor of NF-κB kinase beta (IKKß) activity assay. Lastly, the anti-inflammatory activity of AA in vivo was evaluated by testing TNF production in LPS-stimulated Balb/c mice. KEY RESULTS: AA effectively inhibited TNF-α release with an IC(50) of 2.7 µg/mL. Moreover, AA significantly inhibited both NO production and iNOS expression. It significantly and dose-dependently inhibited TNF and IL-1ß proteins and mRNA expression; as well as IL-6 and KC proteins. Additionally, AA prevented the translocation of NF-κB in both cell lines; suggesting that it is acting at a post receptor level. This was confirmed by AA's ability to inhibit IKKß activity, a kinase responsible for activating NF-κB, hence providing an insight on AA's mechanism of action. Finally, AA significantly reduced TNF production in vivo. CONCLUSIONS AND IMPLICATIONS: This study presents the potential utilization of this compound, as a lead for the development of an anti-inflammatory drug.