Biochemical and Pharmacological Assessments of Tramadol Abuse on Human Male Fertility: Relation to Seminal Plasma 8-Hydroxyguanosine and Zinc.

Tramadol is a pain killing drug highly used worldwide. There is a knowledge gap for fertility consequences of analgesic addiction in men. In this observational study, we investigated the hazards of tramadol abuse on human male reproductive function. A total of 30 tramadol addicts and 30 healthy controls have participated in the study. History and clinical examination of the included subjects were performed. Biochemical and molecular assays were measured in all participants include serum reproductive hormones (calculated free testosterone, FSH, LH, prolactin and estradiol) using ELISA techniques, semen analysis, seminal plasma zinc and selenium assays using colorimetric kits, seminal plasma tramadol concentrations using Gas Chromatography-Mass Spectrometry (GC-MS), and seminal plasma 8-hydroxyguanosine (8-OHG) using high performance liquid chromatography were measured. Tramadol abuse significantly decreased semen parameters quality. Additionally, tramadol abuse significantly decreased testosterone (P = 0.001) and increased prolactin serum levels (P = 0.000). Tramadol abusers showed significantly higher levels of 8-OHG (P < 0.0001) with significantly lower levels of zinc and selenium in their seminal plasma compared with the controls (P < 0.0001, and 0.0002 respectively). Also, tramadol addicts displayed positive correlations between seminal plasma levels of 8-OHG (r = 0.905, P = 0.00) and sperm abnormal forms (r = 0.610, P = 0.000) with seminal plasma tramadol levels. Seminal plasma levels of zinc (r = - 0.815, P = 0.00), sperm motility (r = - 0.484, P = 0.007), and vitality (r = - 0.430, P = 0.018) were negatively correlated with seminal plasma levels of tramadol. Our data suggest that tramadol abuse may impair male fertility by increasing oxidative damage of sperms and reducing testosterone and the antioxidants trace elements in testicular tissues. Supplementary Information: The online version contains supplementary material available at 10.1007/s12291-023-01141-4.

EDSS and infratentorial white matter lesion volume are considered predictors of fatigue severity in RRMS.

Fatigue is a common disabling symptom of relapsing remitting multiple sclerosis (RRMS). Many studies have linked grey matter atrophy to fatigue, but white matter lesion load (WM-LL) has received less attention. Here we assess the relation between fatigue and regional WM-LL volumetric measures. 63 patients with RRMS participated in this study; mean age was 31.9 ± 8.1 years. Each patient provided demographic details and was scored on the expanded disability status scale (EDSS) and fatigue severity scale (FSS). VolBrain, a fully automated, operator-independent tool was used to assess WM-LL and whole brain volume. The patients were classified into three groups: no fatigue (FSS < 4), low to moderate fatigue (FSS ≥ 4 ≤ 5) and high fatigue (FSS > 5). 33.3% of patients had no significant fatigue, 25.4% had mild-to-moderate fatigue, and 41.3% had significant fatigue. Age, disease duration, relapses, and EDSS were positively correlated to fatigue severity (P = 0.034, 0.002, 0.009 and 0.001 respectively). Whole brain volume, total and regional WM-LL (juxtacortical, periventricular, infratentorial) were also correlated with fatigue severity. Ordinal regression analysis for fatigue severity showed EDSS and infratentorial lesion volume were the best predictors. In conclusion, EDSS and infratentorial lesion volume (cerebellar and brainstem) are the best predictors of fatigue severity.

Multidrug resistant 1 (MDR1) C3435T and G2677T gene polymorphism: impact on the risk of acute rejection in pediatric kidney transplant recipients.

BACKGROUND: Tacrolimus is the backbone drug in kidney transplantation. Single nucleotide polymorphism of Multidrug resistant 1 gene can affect tacrolimus metabolism consequently it can affect tacrolimus trough level and incidence of acute rejection. The aim of this study is to investigate the impact of Multidrug resistant 1 gene, C3435T and G2677T Single nucleotide polymorphisms on tacrolimus pharmacokinetics and on the risk of acute rejection in pediatric kidney transplant recipients. METHODS: Typing of Multidrug resistant 1 gene, C3435T and G2677T gene polymorphism was done using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) for 83 pediatric kidney transplant recipients and 80 matched healthy controls. RESULTS: In Multidrug resistant 1 gene (C3435T), CC, CT genotypes and C allele were significantly associated with risk of acute rejection when compared to none acute rejection group (P = 0.008, 0.001 and 0.01 respectively). The required tacrolimus doses to achieve trough level were significantly higher among CC than CT than TT genotypes through the 1st 6 months after kidney transplantation. While, in Multidrug resistant 1 gene (G2677T), GT, TT genotypes and T allele were associated with acute rejection when compared to none acute rejection (P = 0.023, 0.033 and 0.028 respectively). The required tacrolimus doses to achieve trough level were significantly higher among TT than GT than GG genotypes through the 1st 6 months after kidney transplantation. CONCLUSION: The C allele, CC and CT genotypes of Multidrug resistant 1 gene (C3435T) and the T allele, GT and TT genotypes of Multidrug resistant 1 gene (G2677T) gene polymorphism may be risk factors for acute rejection and this can be attributed to their effect on tacrolimus pharmacokinetics. Tacrolimus therapy may be tailored according to the recipient genotype for better outcome.

Fatigue and brain atrophy in Egyptian patients with relapsing remitting multiple sclerosis.

BACKGROUND: Fatigue is the most troublesome symptom in relapsing remitting multiple sclerosis (RRMS). It starts early in the disease course, escalates with disease progression and impacts the patients` quality of life. The aim of this work was to estimate the frequency of fatigue and to evaluate the relationship between severity of fatigue, clinical data, level of disability and volumetric brain atrophy in RRMS. METHODS: 43 RRMS patients with 40 age- and sex-matched normal volunteers were recruited. Demographic and clinical data were recorded. Each participant was assessed with the Expanded Disability Status Scale (EDSS), Fatigue Severity Scale (FSS), Brief Cognitive Assessment for Multiple Sclerosis (BICAMS) and a variety of brain volumetric measures. RESULTS: 31 (72.1%) of RRMS patients were found to have fatigue. There were no significant differences in demographic data between patients with or without fatigue according to FSS. However, patients with fatigue had a higher number of attacks, and higher scores in the EDSS and BICAMS than non-fatigued patients. There was a greater reduction in total brain volume, cerebral grey matter, and brain stem, thalamic and caudate volumes in fatigued compared with the non-fatigued patients and controls. FSS was significantly correlated with patients' age, duration of illness, total number of attacks, EDSS, and BICAMS. Total brain, cerebral grey matter and thalamic volumes all had negative correlations with fatigue severity. Regression analysis showed that EDSS accounted for 46% of the variance in fatigue scores while thalamic and brainstem atrophy accounted for 50.7%. CONCLUSION: Fatigue was fairly common in RRMS patients. Level of disability and atrophy of the thalamus and brain stem were the best predictors of fatigue.

Possible Associations of Disturbed Neurometals and Ammonia with Glycaemic Control in Type 1 Diabetic Children with Attention Deficit Hyperactivity Disorder.

The chronicity of type 1 diabetes mellitus (T1DM) is reported to be associated with various psychological disorders. The current study aimed to evaluate the levels of serum ammonia and various neurometals (zinc, copper, and magnesium) in patients with T1DM with and without ADHD and to correlate their levels with glycaemic status. A prospective case-control study was conducted with 60 diabetic children with T1DM (allocated into a group of 20 patients with a diagnosis of ADHD and a group of 40 patients without ADHD) who were comparable to 60 matched controls. Assays of glucose, glycated haemoglobin (HbA1c), ammonia, zinc, copper, and magnesium were performed. Overall, ammonia and copper levels were significantly higher in the diabetic patients especially those with ADHD than in the control group (p Ë‚ 0.05 for all). The calculated copper/zinc ratio was significantly higher in the diabetic patient group than in the control group and higher in diabetic children with ADHD than in diabetic children without ADHD (p Ë‚ 0.05 for all). Diabetic children had significantly lower magnesium levels than the controls (p Ë‚ 0.05), but no significant difference between the diabetic subgroups was detected. A positive correlation between glycaemic control (HbA1c %) and ammonia level was found in the diabetic group and subgroups, and a positive correlation was found between HbA1c % and the Cu/Zn ratio in diabetic children with ADHD (p Ë‚ 0.05 for all). The current study confirms an association of elevated ammonia and copper/zinc ratio with poor glycaemic control and ADHD development among children with T1DM.

Assessments of Amino Acids, Ammonia and Oxidative Stress Among Cohort of Egyptian Autistic Children: Correlations with Electroencephalogram and Disease Severity.

OBJECTIVE: The current study aimed to assess the profiles of plasma amino acids, serum ammonia and oxidative stress status among autistic children in terms of electroencephalogram findings and clinical severity among the cohort of autistic Egyptian children. PATIENTS AND METHODS: The present study included 118 Egyptian children categorized into 54 children with autism who were comparable with 64 healthy controls. Clinical assessments of cases were performed using CARS in addition to EEG records. Plasma amino acids were measured using high-performance liquid chromatography (HPLC), while, serum ammonia and oxidative stress markers were measured using colorimetric methods for all included children. RESULTS: The overall results revealed that 37.04% of cases had abnormal EEG findings. Amino acid profile in autistic children showed statistically significant lower levels of aspartic acid, glycine, ß-alanine, tryptophan, lysine and proline amino acids with significantly higher asparagine amino acid derivative levels among autistic patients versus the control group (p˂0.05). There were significantly higher serum ammonia levels with significantly higher total oxidant status (TOS) and oxidative stress index (OSI) values among the included autistic children vs controls (p˂0.05). There were significantly negative correlations between CARS with aspartic acid (r=-0.269, P=0.049), arginine (r= - 0.286, p= 0.036), and TAS (r= -0.341, p= 0.012), and significantly positive correlations between CARS with TOS (r=0.360, p= 0.007) and OSI (r= 0.338, p= 0.013). CONCLUSION: Dysregulated amino acid metabolism, high ammonia and oxidative stress were prevalent among autistic children and should be considered in autism management. Still EEG records were inconclusive among autistic children, although may be helpful in assessment autism severity.

Possible Metabolic Alterations among Autistic Male Children: Clinical and Biochemical Approaches.

The present cross-sectional, hospital-based study was carried out on 146 Egyptian male children, 73 males with autism who were comparable with another 73 healthy age- and sex-matched children, recruited from the outpatients' psychiatric clinics of the Neuropsychiatric and Pediatric Departments of South Valley and Assiut University Hospitals, Egypt. Neuropsychological assessments of autistic males were done using CARS, short sensory profile and intelligent quotients. Serum markers of mitochondrial dysfunction (lactate, pyruvate, and lactate to pyruvate ratio, creatine kinase (CK), L-carnitine, ammonia, lactate dehydrogenase, pyruvate kinase, alanine transaminase and aspartate transaminase), oxidative stress and blood levels of heavy metals (mercury, lead and aluminium) were measured. Serum cholesterol, cortisol, free testosterone, estradiol, dehydroepiandrostenedione, adenosine deaminase and Helicobacter pylori antigen in stool were also performed. There was evidence of mitochondrial dysfunction among autistic children. Additionally, there were significantly lower serum total cholesterol, cortisol and estradiol as well as significantly higher dehydroepiandrostenedione (DHEA) and free testosterone (p < 0.05 for all markers). Twenty-eight (38%) cases were positive for H. pylori antigen in their stool with significant higher serum ammonia and lower adenosine deaminase than in H. pylori-negative autistic children. Mitochondrial dysfunction, H. pylori infection and low cholesterol were prevalent among autistic male children, which should be targeted during autism management.

Biochemical assessments of thyroid profile, serum 25-hydroxycholecalciferol and cluster of differentiation 5 expression levels among children with autism.

BACKGROUND: The exact pathogenesis of autism is still unknown. Both thyroid hormones and 25(OH)D are important for brain development, in addition to CD5; all have immunomodulatory actions by which their dysregulation may have a potential role in autism pathogenesis. OBJECTIVES: The objectives of this study were to assess the thyroid profile, serum 25(OH)D levels and CD5 expression levels among autistic patients and to find out the correlations between the measured biomarkers with each other on one side and with the disease severity on the other side. PATIENTS AND METHODS: This cross-sectional case-control study has been conducted on 60 children with autism and 40 controls, recruited from Qena Governorate, Upper Egypt. Childhood Autism Rating Scale (CARS) score was used to assess the included patients. Biochemical assays of thyroid function in the form of free triiodothyronine (FT3), free tetraiodothyronine (FT4), thyroid-stimulating hormone (TSH) and 25(OH)D were done using commercially available enzyme-linked immunosorbent assay (ELISA) kits, while CD5 expression levels were measured using flow cytometry (FCM) analysis for all the included patients and controls. RESULTS: The overall measurement results show significant higher mean serum TSH levels, mean CD5 expression levels with significant lower mean serum 25(OH)D levels among autistic children when compared with the control group (p<0.05 for all). Significant negative correlations between CD5 with FT3, FT4 and 25(OH)D were observed. CARS score showed significant negative correlations with both FT3 and 25(OH)D, while it was positively correlated with CD5 in a significant manner (p<0.05 for all). CONCLUSION: Elevated CD5 expression and decreased 25(OH)D stores could play a potential role in the pathogenesis of autism via their immune-modulator actions. High TSH serum levels among autistic children, although within the physiological range, reflect the presence of thyroid dysfunction among such children, which needs further assessment.

Evaluation of gastro-oesophageal reflux disease in wheezy infants using 24-h oesophageal combined impedance and pH monitoring.

BACKGROUND AND STUDY AIMS: Gastro-oesophageal reflux disease (GERD) is incriminated as a cause of non-asthmatic infantile wheeze. To date, no diagnostic test is considered standard for GERD-related airway reflux diagnosis. Oesophageal combined multiple channel intraluminal impedance and pH (MII-pH) monitoring is proposed to be a sensitive tool for evaluation of all GERD including infantile wheeze. We aimed to determine the GERD prevalence amongst wheezy infants in the first year of life using combined MII-pH versus pH monitoring alone and evaluate the sensitivity and specificity of objective MII-pH monitoring parameters in GERD-associated infantile wheeze diagnosis compared to those of lipid-laden macrophage index (LLMI). PATIENTS AND METHODS: Thirty-eight wheezy infants below 1year of age were evaluated for GERD using oesophageal combined MII-pH monitoring and LLMI. RESULTS: Totally, 60.5% of cases had abnormal MII-pH; only 7.9% of them had abnormal pH monitoring. LLMI was significantly higher in wheezy infants with abnormal MII-pH than infants with normal MII-pH monitoring (112±88 versus 70±48; P=0.036). The current definitions of abnormal MII-pH study, reflux index≥10% and distal reflux episodes≥100, had low sensitivity (23%) but high specificity (100% and 96%, respectively) in GERD-related aspiration diagnosis defined by LLMI≥100. Using ROC curves, bolus contact time≥2.4% and proximal reflux episodes≥46 had 61% and 54% sensitivity and 64% and 76% specificity, respectively, in GERD-related aspiration diagnosis. CONCLUSION: Combined MII-pH is superior to pH monitoring in reflux-associated infantile wheeze diagnosis. Objective data including proximal reflux episodes and bolus contact time should be combined with the current parameters used in reflux-associated infantile wheeze diagnosis.

Unilateral Emphysema in Infancy, a Rare Presentation of Aberrant Bronchial Artery: Case Report and Review of Literature.

Aberrant bronchial arteries are rarely seen and may originate from various vascular structures. Hemoptysis is the most common clinical presentation of cases with anomalous bronchial artery. We report a case of a 1-month-old infant presented with respiratory distress and left lung emphysema. Radiologic investigations and bronchoscopy revealed that the cause is an aberrant left bronchial artery compressing the left main bronchus. Surgical division of the aberrant vessel was performed with gradual improvement of the emphysema and respiratory distress. Unilateral emphysema due to vascular compression was previously reported. However, to the best of our knowledge, this is the first reported case of aberrant bronchial artery presenting with external compression of a main bronchus and unilateral emphysema. Also, this is the youngest reported case with an aberrant bronchial artery.

Clinical Utility of Bronchoalveolar Lavage Pepsin in Diagnosis of Gastroesophageal Reflux among Wheezy Infants.

Background. There is no gold standard test for diagnosis of gastroesophageal reflux disease (GERD) associated infantile wheezing. Objectives. To evaluate the value of bronchoalveolar lavage (BAL) pepsin assay in diagnosis of GERD in wheezy infants. Methods. Fifty-two wheezy infants were evaluated for GERD using esophageal combined impedance-pH (MII-pH) monitoring, esophagogastroduodenoscopy with esophageal biopsies, and BAL pepsin. Tracheobronchial aspirates from 10 healthy infants planned for surgery without history of respiratory problems were examined for pepsin. Results. Wheezy infants with silent reflux and wheezy infants with typical GERD symptoms but normal MII-pH had significantly higher BAL pepsin compared to healthy control (45.3 ± 8.6 and 42.8 ± 8 versus 29 ± 2.6, P < 0.0001 and P = 0.011, resp.). BAL pepsin had sensitivity (61.7%, 72 %, and 70%) and specificity (55.5%, 52.9%, and 53%) to diagnose GERD associated infantile wheeze compared to abnormal MII-pH, reflux esophagitis, and lipid laden macrophage index, respectively. Conclusion. A stepwise approach for assessment of GERD in wheezy infants is advised. In those with silent reflux, a trial of antireflux therapy is warranted with no need for further pepsin assay. But when combined MII-pH is negative despite the presence of typical GERD symptoms, pepsin assay will be needed to rule out GERD related aspiration.

Endobronchial inflammatory pseudotumor: a rare cause of a pneumothorax in children.

Inflammatory pseudotumors of the lung are a group of non-neoplastic tumors, which are mainly of parenchymal origin and rarely endobronchial. We report a case of a 9-year-old girl who presented with left-sided tension pneumothorax and subcutaneous emphysema. After emergency management, chest computed tomography revealed an ill-defined left lung mass. Rigid bronchoscopy revealed a mass occluding the left main bronchus at the origin of the left upper lobe bronchus. Initially, the mass was thought to be a foreign body granuloma. Few weeks later, the child presented with recurrence of the same clinical, radiologic, and bronchoscopic outcomes. Histologic examination after the repeat bronchoscopic excision revealed the lesion to be consistent with inflammatory pseudotumor. Left upper lobectomy was performed with a complete resolution of symptoms and no recurrence was observed during the 2 years of follow-up. To the best of our knowledge, this is the first reported case of inflammatory pseudotumor presenting with tension pneumothorax.