A Clinical Study of Urine Amino Acids in Children with Autism Spectrum Disorder.

Amino acids are organic compounds that enter the protein structure, being involved in the proper functioning of the body. The role of amino acids in the onset of autism spectrum disorder (ASD) is yet to be established. Our aim was to identify correlations between urine amino acids and their derivatives and ASD. METHODS: We designed a case-control study that consisted of 75 boys and girls, aged between 2 and 12 years. For amino acid profile, we used urine samples that were analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). RESULTS: Descriptive analysis showed higher values for glutamine, hydroxyproline, tyrosine, aspartic acid, and tryptophan and lower values for serine in the autism group than in the control group. Also, we found that boys with autism had higher values than the boys in the control group for serine, threonine, and aspartic acid. For girls from both groups, we did not find statistically significant values. In terms of age groups, we found significantly higher values for histidine, threonine, valine, methionine, aspartic acid, glutamic acid, alpha amino-adipic acid, sarcosine, alanine, and beta-alanine and significantly lower values for proline for both the autism and control groups under 5 years. CONCLUSIONS: The findings of this study support the assumption that amino acids may have a role in the expression of ASD.

Serum Amino Acid Profiling in Children with Autistic Spectrum Disorder: Insights from a Single-Center Study in Southern Romania.

The objective of this study was to analyze the serum amino acid profile in children diagnosed with autistic spectrum disorder (ASD) in southern Romania. The analysis aimed to provide insights into the underlying metabolic dysregulations associated with ASD. ASD is a neurodevelopmental disorder characterized by impaired social interaction, communication deficits, and restricted repetitive behaviors. Although the exact cause of ASD is largely unknown, recent evidence suggests that abnormalities in amino acid metabolism may contribute to its pathogenesis. Therefore, studying the amino acid profile in children with ASD could offer valuable information for understanding the metabolic disturbances associated with this complex disorder. This single-center study examined serum samples from children diagnosed with ASD, utilizing advanced analytical techniques to quantify the levels of different amino acids, amino acid derivatives, and amino acid-like substances. The results showed a lower level of taurine and a higher level of asparagine and leucine in the ASD group versus the control group. In the ASD group, we observed significant differences in tryptophan and alpha-aminobutyric acid levels based on age, with higher tryptophan levels in children older than 7 years when compared to children younger than 7 years; however, no significant correlations were found with the ASD group older than 7 years old. Additionally, younger children with ASD exhibited higher levels of alpha-aminobutyric acid than older children with ASD. The findings from this study contribute to the growing body of knowledge on the metabolic aspects of ASD, highlighting potential biomarkers and therapeutic targets for improving the management and treatment of ASD in children.

Micronutrient Research in Autism Spectrum Disorder. A Clinical Study.

Autistic spectrum disorders are part of the category of neurodevelopmental disorders, characterized by: difficulties in communication and social interaction, restrictive and repetitive patterns of behaviours and activities, which are present throughout the developmental period, and can be diagnosed in the first five years of life. Due to the increase in the incidence of this disorder in recent years, it has become a topic of great interest both to specialists in child and adolescent psychiatry and to researchers in the field. Given the polymorphism of Autism Spectrum Disorder and the need to discover factors that better explain the etiology of this disorder, studies related to biomarkers are extremely varied. One of the areas of study that have exercised particular interest is related to the involvement of metals in the pathology of autism spectrum disorder. Apart from the controversies related to heavy metals that according to studies affect the developmental process, there are studies that suggest that some micronutrients such as zinc, copper, selenium, iron, magnesium, may be involved in the etiology of autism spectrum disorder. Starting from these studies, we set out to investigate to what extent these essential metals for the body are involved in the etiology of autism spectrum disorder and how they influence the severity of symptoms.

Clostridoides difficile Infection Severity Assessment by Fecal Calprotectin: A Pilot Study.

Clostridoides difficile infection (CDI) is the leading cause of antibiotic related diarrhea therapy and may associate high morbidity and mortality. Providing a potential biomarker to assess disease severity may help physicians in choosing the right treatment. METHODS: This was a prospective, single-centre cohort study which included patients diagnosed with CDI which were assessed by fecal calprotectin (FC). RESULTS: Patients included had a mean of 69.29 years of age, 54.23% of male gender. Patients diagnosed with mild CDI had a mean ATLAS score of 3.39 (±1.24), statistically lower (p<0.001) than patients with severe CDI who had a mean ATLAS score of 7.33 (±0.77). Fecal calprotectin concentrations were significantly higher (p<0.001) in the severe CDI patients (615.14µg/g; IQR, 403.62-784.4µg/g) than in the mild CDI patients (195.42µg/g; IQR, 131.12-298.59µg/g). We suggest a cut-off of 290.09µg/g for the predictive marker of fecal calprotectin, which permitted to identify patients with severe and mild CDI, having 100% sensitivity and 76% specificity. CONCLUSIONS: Our findings point out the potential that FC might have, as a biomarker for disease severity. However, future multicentre studies and in larger cohort need to validate the results.

Antibiotic Resistance, Still a Global Challenge.

The use of antibiotics represents a major health problem worldwide because they are often administered without medical prescription. This has led to different situations starting from a large use in inappropriate cases without medical recommendation, to a major issue that represents antimicrobial resistance. Our aim was to identify the opinion of healthcare workers (physicians and pharmacists) about the most effective solution at reducing antimicrobial resistance, helping the policy makers to take a decision. The present study was conducted from March 15th, 2021 to April 15th, 2021, using a virtual questionnaire. A total of 397 respondents provided a complete response to our questionnaire: 313 physicians and 84 pharmacists. Our results provided valuable insights that can be used to inform the development of a national health policy, resulting in population health gains. Our work provided an indication of physicians' preferences toward solutions as "A tax on antibiotic consumption, which could be used to fund innovation strategies." (41.53%) and "An educational program for patients that highlights the causes and effects of antimicrobial resistance." (42.49%). The pharmacists preferred the solutions as "An educational program for patients that highlights the causes and effects of antimicrobial resistance." (52.38%) and "Elimination of antibiotics from the list of the emergency pharmaceutical services." (42.86%). A small number of physicians (2.24%) and pharmacists (3.57%) recommended as the most effective solution at reducing antimicrobial resistance "Restrain antibiotic use in the food industry."

Clostridioides difficile Infection among Cirrhotic Patients with Variceal Bleeding.

Clostridioides difficile infection (CDI) stands as the leading cause of nosocomial infection with high morbidity and mortality rates, causing a major burden on the healthcare system. Driven by antibiotics, it usually affects older patients with chronic disease or immunosuppressed or oncologic management. Variceal bleeding secondary to cirrhosis requires antibiotics to prevent bacterial translocation, and thus patients become susceptible to CDI. We aimed to investigate the risk factors for CDI in cirrhotic patients with variceal bleeding following ceftriaxone and the mortality risk in this patient's population. We retrospectively screened 367 cirrhotic patients with variceal bleeding, from which 25 patients were confirmed with CDI, from 1 January 2017 to 31 December 2019. We found MELD to be the only multivariate predictor for mortality (odds ratio, OR = 1.281, 95% confidence interval, CI: 0.098-1.643, p = 0.042). A model of four predictors (age, days of admission, Charlson index, Child-Pugh score) was generated (area under the receiver operating characteristics curve, AUC = 0.840, 95% CI: 0.758-0.921, p < 0.0001) to assess the risk of CDI exposure. Determining the probability of getting CDI for cirrhotic patients with variceal bleeding could be a tool for doctors in taking decisions, which could be integrated in sustainable public health programs.

Urinary tract infection with Klebsiella pneumoniae in Patients with Chronic Kidney Disease.

Study Motivation: After assessing electronic databases of medical scientific literature, we have observed that the interrelation between urinary tract infections (UTIs) and chronic kidney disease (CKD) is poorly studied, especially when UTIs are caused by Klebsiella pneumoniae (K. pneumoniae). MATERIALS AND METHODS: K. pneumoniae was isolated in 14 urine samples from patients with CKD addmited in the Nephrology Department of the County Emergency Clinical Hospital Craiova. The isolated strains were statistically analyzed in the correlation with the different clinical and functional parameters (age, gender, CKD stage, comorbidities, biochemical parameters-serum urea, creatinine, uric acid and blood electrolytes). The degree of K. pneumoniae susceptibility to antibiotics from different pharmacodynamic classes was assessed. RESULTS: UTIs with K. pneumoniae in patients with CKD in the investigated period represented 0.51% from the total admissions in the clinic and 32.60% from cases of UTI. Eleven patients with this type of infection (78.56%) were in stage 4 and 5 CKD, and from them 4 also had diabetes mellitus type 2 (28.57%). We observed an increased level for serum creatinine (100%), blood urea (85.71%), and serum uric acid (45.45%). Two patients died after installation of cardiovascular changes in CKD, at advanced ages and in the presence of urinary infection. Multiple drug resistance occurred in 6 strains of K. pneumoniae correlated with the degree of kidney failure, advanced age, male gender, and diabetes mellitus. CONCLUSIONS: UTI with K. pneumoniae in patients with CKD is the second cause of urinary infection which raises problems of unfavorable evolution of CKD and also the recurrence of UTI with multiple drug resistance in CKD, which may lead to pharmacotherapeutical problems.

Role of transforming growth factor ß-connective tissue growth factor pathway in dihydropyridine calcium channel blockers-induced gingival overgrowth.

BACKGROUND: Gingival overgrowth was reported as a side effect after chronic administration of several drugs, which, despite their different pharmacological effect, seem to have the gingival mucosa as a secondary target. The thickness of the gingival epithelium and fibrosis in the lamina propria are unspecific changes that together determine the enlargement of the gingival mucosa, but the molecular mechanisms responsible for the imbalance of collagen synthesis/breakdown are still uncertain. The aim of our study was to assess the role of TGF-ß1-CTGF pathway in the activation of cells with a fibrilogenetic phenotype responsible for the gingival fibrosis developed after chronic administration of dihydropyridine calcium channel blockers. MATERIALS AND METHODS: Fragments of gingival tissue collected from patients clinically diagnosed with gingival overgrowth after chronic administration of nifedipine and amlodipine were processed for paraffin embedding. Serial sections were used for routine staining Masson and Gömöri's silver impregnation in order to reveal collagen accumulation and for immunohistochemical reactions to label TGF-ß1, CTGF, Ki67 and α-SMA. RESULTS: Routine histological staining for collagen revealed the presence of gingival fibrosis and a change between type I collagen/type III collagen ratio. Regardless of the drug involved, many slides showed extended TGF-ß1 positive areas, mainly in the profound - spinous and basal - layers, but also in some cells from the subjacent connective tissue. CTGF exposed intense positive reaction in the basal and parabasal layers, but also in resident cells from the connective tissue. Ki67 immunolabeling did not reveal an increased fibroblast proliferation in the lamina propria. We noticed the presence of a small number of myofibroblasts in the lamina propria. CONCLUSIONS: These findings suggest that TGF-ß1-CTGF axis is activated in dihydropyridine calcium channel blockers-induced gingival overgrowth and exerts a different control on the activation of fibroblasts with a synthetic phenotype. These results also have implications for better understanding mechanisms of fibrosis and the future use of this pathogenic pathway as a therapeutic target in order to limit gingival fibrosis.

Pharmacological mechanisms underlying the association of antipsychotics with metabolic disorders.

Obesity and metabolic syndrome in association with an increased risk of cardiovascular disease and type II diabetes are significant problems that contribute to lower life expectancy of patients with schizophrenia. Understanding the pharmacological mechanisms of the current antipsychotic treatment is clearly the key to the improvement of pharmacotherapy, to avoid or to mitigate the metabolic adverse effects.

Acetylsalicylic Acid in migraine with aura prevention - a retrospective study.

In a retrospective study we evaluated the efficacy and tolerability of Acetylsalicylic Acid (ASA), an antiplatelet drug, in the prophylactic treatment of migraine with aura (MA). We reviewed the charts of 203 patients suffering from MA according to the ICHD II criteria, attending to Turin University Headache Centre. 95 subjects (46.8%) were treated with ASA at low dose, 108 (53.2%) with other prophylactic therapies normally used for migraine for a period that ranged from at least 4 months to 194 months. Eighty-four patients (88.4%) treated with ASA referred positive results, while only 64 patients (59.3%) who underwent other prophylactic treatments did (p < 0.001). The attacks' frequency of patients treated with ASA decreased significantly from 3.83±1.57 pre-treatment to 1.38±0.87 after treatment (p<0.001). Aura duration was markedly reduced from 36.21±19.80 pre-treatment to 22.0±15.5 after treatment (p<0.001). ASA was well-tolerated. ASA is a safe drug with minor possible side effects that can be routinely used when prophylactic treatment of MA is required.

Contributions to the study of morphofunctional interrelations in the liver of the rats treated with certain antipsychotic drugs.

The issue of antipsychotics in psychiatry constituted a revolution at the time. The firsts, starting with chlorpromazine represent the conventional antipsychotics, in the last decades there was a new generation of antipsychotics, atypical, which improved the results in treating psychoses. Because, as any drug, it may have adverse effects we aimed an experimental study on rats to observe the toxic potential on liver of both generations of antipsychotics. From the first generation we used chlorpromazine, haloperidol and haloperidol decanoate and from the second, aripiprazole and risperidone. Results of the study show an increased toxicity of chlorpromazine and diminished among the others, without being the same for every drug.

Effect of propranolol on mepivacaine serum concentrations in dental practice.

OBJECTIVE: The objective of this study was to determine the effect of propranolol pretreatment on mepivacaine serum concentrations in dental patients. STUDY DESIGN: In a double blind, randomized, 2-way crossover study, 10 patients ingested 30 mg propranolol or placebo, 2 hours before local anesthesia for dental scaling. Each subject received a single dose of 51 mg mepivacaine for posterior superior alveolar nerve block. Mepivacaine in venous serum was measured for up to 1 hour, after 5, 15, 30, 45, and 60 minutes from injection. Serum concentrations of mepivacaine were determined by gas chromatography. Blood pressure and heart rate were measured before and after propranolol or placebo and after each sampling. RESULTS: Peak serum concentrations of mepivacaine, C(max) (1.214 +/- 0.746 microg/mL(-1)), were significantly increased by propranolol (2.249 +/- 1.559 microg/mL(-1), P < .05). Propranolol pretreatment reduced blood pressure and heart rate. CONCLUSION: Although propranolol pretreatment increased almost doublefold mepivacaine serum concentrations and reduced blood pressure and heart rate, mepivacaine can be used safely in dental patients taking propranolol for short-duration interventions.

[Visual evoked potentials in the in evaluation of the safety profile of levocetirizine]. / Potentiale evocate vizual în evaluarea profilului de siguranta al levocetirizinei.

UNLABELLED: Because human histamine H1 receptors were visualized at different brain levels, we evaluated the effects of levocetirizine (LCZ) on the visual evoked potentials (VEP). MATERIAL AND METHOD: Eighteen volunteer subjects were included in a placebo-controlled study, VEP recordings (pattern-reversal technique) were performed at baseline and 240 min. post-medication, and the N75-P100-N135 complex parameters (latency, duration, amplitude and surface of the components) were measured in the leads FzOL5, FzOz and FzOR5. RESULTS: LCZ 5 mg p.o. induced no statistically significant changes, neither in the mean values of all P100 parameters, nor in the mean latency of N75 and N135 components. No unilateral or bilateral alterations of VEP parameters were detected, suggesting that LCZ has no influence on the functional integrity of visual sensorial pathway. CONCLUSION: Our study may initiate a novel approach in the neurological safety profile evaluation of new H, antihistamines using VEP, with the advantage of no radiological exposure.

A review of antisense therapeutic interventions for molecular biological targets in asthma.

Modern tools of genomics and proteomics reveal potential therapeutic antisense targets in asthma, increasing the interest in the development of anti-mRNA drugs. In allergic asthma experimental models, antisense oligonucleotides (ASO) are administered by inhalation or systemically. ASO can be used for a large number of molecular targets: cell membrane receptors (G-protein coupled receptors, cytokine and chemokine receptors), membrane proteins, ion channels, cytokines and related factors, signaling non-receptor protein kinases (tyrosine kinases, and serine/threonine kinases) and regulators of transcription belonging to Cys4 zinc finger of nuclear receptor type or beta-scaffold factors with minor groove contacts classes/superclasses of transcription factors. A respirable ASO against the adenosine A(1) receptor was investigated in human trials. RNase P-associated external guide sequence (EGS) delivered into pulmonary tissues represents a potentially new therapeutic approach in asthma as well as ribozyme strategies. Small interfering RNA (siRNA) targeting key molecules involved in the patho-physiology of allergic asthma are expected to be of benefit as RNAi immunotherapy. Antagomirs, synthetic analogs of microRNA (miRNA), have important roles in regulation of gene expression in asthma. RNA interference (RNAi) technologies offer higher efficiency in suppressing the expression of specific genes, compared with traditional antisense approaches.