Neuroprotective Effects of Phytochemicals against Aluminum Chloride-Induced Alzheimer's Disease through ApoE4/LRP1, Wnt3/ß-Catenin/GSK3ß, and TLR4/NLRP3 Pathways with Physical and Mental Activities in a Rat Model.

BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative disorder that is associated with abnormal cognition. AD is aided in its initiation and progression by hereditary and environmental factors. Aluminum (Al) is a neurotoxic agent that causes oxidative stress, which is linked to AD progression. Additionally, Nrf2/HO-1, APOE4/LRP1, Wnt3/ß-catenin, and TLR4/NLRP3 are the main signaling pathways involved in AD pathogenesis. Several phytochemicals are promising options in delaying AD evolution. OBJECTIVES: This study aimed at studying the neuroprotective effects of some phytochemicals as morin (MOR), thymol (TML), and thymoquinone (TMQ) on physical and mental activities (PhM) in Al chloride (AlCl3)-induced AD rat model. Another objective was to determine the specificity of phytochemicals to AD signaling pathways using molecular docking. METHODS: Eighty male Dawley rats were divided into eight groups. Each group received: saline (control group), AlCl3, (ALAD), PhM, either alone or with a combination of MOR, TML, and/or TMQ for five weeks. Animals were then subjected to behavioral evaluation. Brain tissues were used for histopathological and biochemical analyses to determine the extent of neurodegeneration. The effect of phytochemicals on AlCl3-induced oxidative stress and the main signaling pathways involved in AD progression were also investigated. RESULTS: AlCl3 caused a decline in spatial learning and memory, as well as histopathological changes in the brains of rats. Phytochemicals combined with PhM restored antioxidant activities, increased HO-1 and Nrf2 levels, blocked inflammasome activation, apoptosis, TLR4 expression, amyloide-ß generation, and tau hyperphophorylation. They also brought ApoE4 and LRP1 levels back to normal and regulated Wnt3/ß-catenin/GSK3ß signaling pathway. CONCLUSIONS: The use of phytochemicals with PhM is a promising strategy for reducing AD by modulating Nrf2/HO-1, TLR4/NLRP3, APOE4/LRP1, and Wnt3/ß-catenin/GSK-3ß signaling pathways.

Neuroprotective Effect of Morin Hydrate against Attention-Deficit/Hyperactivity Disorder (ADHD) Induced by MSG and/or Protein Malnutrition in Rat Pups: Effect on Oxidative/Monoamines/Inflammatory Balance and Apoptosis.

Monosodium glutamate (MSG) is one of the most widely used food additives. However, it has been linked to protein malnutrition (PM) and various forms of toxicities such as metabolic disorders and neurotoxic effects. The current study is the first to explore the association between MSG, PM, and induced brain injury similar to attention-deficit/hyperactivity disorder (ADHD). Moreover, we determined the underlying mechanistic protective pathways of morin hydrate (MH)-a natural flavonoid with reported multiple therapeutic properties. PM was induced by feeding animals with a low protein diet and confirmed by low serum albumin measurement. Subsequently, rat pups were randomized into seven groups of 10 rats each. Group I, III, and VI were normally fed (NF) and groups II, IV, V, and VII were PM fed. Group I served as normal control NF while Group II served as PM control animals. Group III received NF + 0.4 g/kg MSG, Group IV: PM + 0.4 g/kg MSG, Group V: PM + 60 mg/kg MH, Group VI: NF + 0.4 kg/g MSG + 60 mg/kg MH and Group VII: PM + 0.4 kg/kg MSG + 60 mg/kg MH. At the end of the experimental period, animals were subjected to behavioral and biochemical tests. Our results showed that treatment of rats with a combination of MSG + PM-fed exhibited inferior outcomes as evidenced by deteriorated effects on behavioral, neurochemical, and histopathological analyses when compared to rats who had received MSG or PM alone. Interestingly, MH improved animals' behavior, increased brain monoamines, brain-derived neuroprotective factor (BDNF), antioxidant status and protein expression of Nrf2/HO-1. This also was accompanied by a significant decrease in brain MDA, inflammatory markers (NF-kB, TNF-α and IL1ß), and suppression of TLR4/NLRP3/caspase-1 axis. Taken together, MSG and/or PM are associated with neuronal dysfunction. Our findings suggest MH as a potential neuroprotective agent against brain insults via targeting Nrf2/HO-1 and hindering TLR4/NLRP3 inflammasome signaling pathways.

Effect of cerebrolysin on neurodevelopmental outcome of high risk preterm infants: A randomized controlled trial.

BACKGROUND: A significant proportion of preterm infants experience developmental delay despite receiving a post discharge early interventional care. Cerebrolysin is a peptide mixture which acts similar to endogenous neurotrophic factors through promoting neurogenesis and enhancing neuronal plasticity. OBJECTIVE: To compare the effect of Cerebrolysin plus routine intervention program versus routine intervention program alone on the outcome of preterm infants at high risk for neurodevelopmental delay. METHODS: In a randomized controlled trial, high-risk preterm infants < 32 weeks' gestation who have abnormal neurological assessment at two months corrected post-natal age were randomized at 6 months corrected post natal age to receive either early intervention program or early intervention program plus Cerebrolysin injection of 0.1 mL/kg body weight every week for 3 months as an adjuvant therapy. The primary outcome was the rate of failure of the gross motor assessment at 12 months of corrected age and secondary outcomes included fine motor, language, and personal social development at 12 months corrected post-natal age as assessed by Denver Developmental Screening Test II. RESULTS: Cerebrolysin group had a significant lower number of infants diagnosed with failed gross motor development compared to infants in the routine intervention group [10 (33%) versus 21 (70%), p = 0.009]. Cerebrolysin group had a significant lower number of infants diagnosed with failed fine motor, language and personal social development compared to infants in the routine intervention group. CONCLUSION: Cerebrolysin, as an adjuvant therapy to routine early interventional care, may improve gross motor development of high-risk preterm infants at 12 months corrected post-natal age.

Combined immunodeficiency (CVID and CD4 lymphopenia) is associated with a high risk of malignancy among adults with primary immune deficiency

Primary immunodeficiency disorders (PID) are a group of heterogeneous disorders characterized by recurrent infections, autoimmunity, increased lymphoproliferative disorders and other malignancies. PID is classified into cellular or humoral disorders or a combination of both. We evaluated the clinical differences among adult patients with three variants of PID: common variable immunodeficiency (CVID), idiopathic CD4 lymphopenia (ICL) and combined immunodeficiency (CID). We retrospectively compared demographics, immunological characteristics, clinical presentations and outcomes of CVID, CID and ICL patients followed from 2012 to 2018. In our cohort, we identified 44 adult patients diagnosed with CVID (22), CID (11) and ICL (11). Malignancy was associated with CID, as seven of 11 patients in this group were diagnosed with malignancy compared to CVID (three of 22) or ICL (two of 11) (P = 0·002 and 0·03, respectively). Malignancies were also linked to male gender [odds ratio (OR) = 5, 95% confidence interval (CI) = 1·12-22·18) P = 0·0342] and a low ratio of CD4/CD8 < 0·8 (OR = 5·1, 95% CI = 1·22-21·28, P = 0·025). Among CID and ICL, two of 11 patients died in each group, while no death was documented among CVID group (P = 0·04). Autoimmune manifestations did not differ between groups. Similarly, the rate of infections was similar between groups, although infectious agents vary. CID is associated with a high risk of malignancy compare to CVID or ICL. Among adults with PID, male gender, low CD4 and a CD4/CD8 ratio of < 0·8 may serve as risk factors of concomitant malignancy. Surveillance of lymphocyte subpopulations should be considered for all adults.

[Tick-borne relapsing fever : An unrecognized cause of fever in travellers]. / La fièvre récurrente à tiques : une cause méconnue de fièvre du voyageur.

INTRODUCTION: Tick-borne relapsing fever is a usual cause of fever in West Africa. Except relapsing febrile episodes, there are no pathognomonic signs and diagnosis is difficult because Borrelia density in patient's blood is low. CASE REPORTS: Tick-borne relapsing fever was revealed by the presence of spirochetes in a blood sample to search malaria in two men, 24 and 31 year-old, returned from Mali. CONCLUSION: This diagnosis should be evocated in patients having fever after a trip in infested area, as malaria, both infections can be associated.

Alopecia areata in patients with systemic lupus erythematosus treated with belimumab: a plausible association.

Belimumab, an anti-B-lymphocyte stimulator monoclonal antibody, was recently approved for the treatment of systemic lupus erythematosus. Alopecia areata is characterized by an acute immune-mediated hair loss. Herein, we report on three adult systemic lupus erythematosus patients who developed alopecia areata in association with belimumab treatment. Alopecia areata was resolved in all three patients and belimumab was discontinued in two of them. Thus, in the current report, we explore the plausible link between alopecia areata and belimumab.

Depression and anxiety symptoms in cardiac patients: a cross-sectional hospital-based study in a Palestinian population.

BACKGROUND: Mental health problems have an adverse effect on the course of cardiac disease. The integration of their diagnosis and treatment into cardiology care is generally poor. It is particularly challenging in cultural environments where mental health problems are stigmatized. The objective of the current study was to investigate the proportion of cardiac patients with depression and anxiety as well as factors associated with the presence of these symptoms in a Palestinian population. METHODS: This cross-sectional hospital-based study was conducted on patients consecutively admitted with a new or existing cardiac diagnosis to one of the four main hospitals in Nablus, Palestine over an eight-month period. Data was obtained from hospital medical charts and an in-person interview, using a structured questionnaire with a sequence of validated instruments. All subjects were screened for depression and anxiety using the Cardiac Depression Scale (CDS) and the Depression Anxiety Stress Scale (DASS-42). Multivariate ordered logistic regression analyses were performed to identify factors among four categories (socio-demographic, clinical, psychosocial, lifestyle) independently associated with depression and anxiety. RESULTS: In total, 1053 patients with a confirmed cardiac diagnosis were included in the study with a participation rate of 96%. Based on the CDS and DASS-42, 54% met the criteria for severe depression (CDS > 100) and 19.2% for severe-to-very severe anxiety (DASS-anxiety > 15), respectively. Symptoms of depression and anxiety were more prevalent among females and less educated patients. Factors independently associated with both depressive and anxiety symptoms were post-traumatic stress disorder symptoms, low level of self-esteem, high somatic symptoms, low physical and mental health component scores, active smoking, physical inactivity, and longer disease duration. Patients with depressive and anxiety symptoms also reported poor social support and lower resilience. CONCLUSION: There was a high level of depression and anxiety in this sample of cardiac patients. The results point to characteristics of patients in particular need for mental health screening and suggest possible targets for intervention such as strengthening of social support and of physical activity. The integration of mental health services into cardiac rehabilitation in Palestine and comparable cultural settings is warranted from the time of first diagnosis and onward.

Angiotensin II type 2 receptor gene polymorphisms and serum angiotensin-converting enzyme level in Egyptian children with systemic lupus erythematosus.

BACKGROUND: There are no reports about the association of angiotensin II type 2 receptor ( AT2R) gene polymorphisms and susceptibility to systemic lupus erythematosus (SLE) in children. OBJECTIVE: The objective of this research is to study AT2R gene polymorphisms in exon 3 (C1593A) and intron 1 (A1675G) in Egyptian children with SLE and its correlation with disease manifestations and serum angiotensin-converting enzyme (ACE) level. METHODS: Typing of AT2R gene polymorphisms was conducted in 123 children with SLE in comparison with 100 healthy controls using the restriction fragment length polymorphism method. RESULTS: Significant differences were found between SLE patients and controls for A-containing genotypes (CA + AA) and A-allele frequencies of AT2R in exon 3 (C1593A) ( p = 0.01, odds ratio (OR) = 2.5, 95% confidence interval (CI) = 1.3-5.05; p = 0.01, OR = 2.2, 95% CI = 1.2-4.1, respectively). G-containing genotypes (AG + GG) and G allele of AT2R in intron 1 (A1675G) were more frequent in SLE patients compared to controls ( p = 0.01, OR = 2.3, 95% CI = 1.2-4.5; p = 0.02, OR = 2.1, 95% CI = 1.2-3.7, respectively). Serum ACE level was significantly higher in SLE patients than in controls ( p < 0.001). There was no association between AT2R gene polymorphisms and ACE level in serum. Moreover, there was no association between AT2R gene polymorphisms and SLE clinical manifestations. CONCLUSION: AT2R gene polymorphisms can be considered risk factors for SLE development in Egyptian children.

Angiotensin-converting enzyme insertion/deletion gene polymorphism in Egyptian children with systemic lupus erythematosus: a possible relation to proliferative nephritis.

Introduction Angiotensin-converting enzyme (ACE) is crucial in the pathogenesis of systemic lupus erythematosus through angiotensin II which regulates vascular tone and endothelial functions. Objectives To study the frequency of ACE insertion/deletion (I/D) gene polymorphism in Egyptian children with systemic lupus erythematosus and its possible relation to the renal pathology in cases with lupus nephritis. Subjects and methods The frequency of ACE gene insertion/deletion polymorphism genotypes was determined in 78 Egyptian children with systemic lupus erythematosus and compared to a matched group of 140 healthy controls using polymerase chain reaction. Results The DD genotype of the ACE gene was higher in systemic lupus erythematosus patients when compared to controls ( P<0.0001; odds ratio (OR) 2.4; 95% confidence interval (CI) 1.7-3.3) and the D allele was more frequent than the I allele in systemic lupus erythematosus patients in comparison to controls ( P < 0.0001; OR = 2.2; 95% CI = (1.6-3.1). In the lupus nephritis group, the DD genotype was significantly higher in those with proliferative lupus nephritis when compared to those with non-proliferative lupus nephritis ( P = 0.02; OR = 1.45; 95% CI = 1.4-1.6). Also, patients with proliferative lupus nephritis showed a higher frequency of the D allele ( P < 0.001; OR = 1.98; 95% CI = 1.3-2.9). Conclusion The D allele and DD genotype of the ACE gene appear to be a risk factor for the susceptibility of systemic lupus erythematosus and occurrence of proliferative nephritis in Egyptian children.

Epidemiological, clinical and laboratory features of murine typhus in central Tunisia.

OBJECTIVE: Murine typhus is an endemic zoonosis. It is difficult to diagnose because of its non-specific clinical manifestations. Our objective was to describe the epidemiological, clinical, laboratory, and treatment features of murine typhus. METHODS: We conducted a retrospective study of 73 adult patients hospitalized for murine typhus from 2006 to 2011. The diagnosis was confirmed by a single titer of IgM≥128 or by seroconversion to typhus group antigen identified by indirect fluorescent assay. RESULTS: The mean age of patients was 33.1 years (range, 13-68 years). Thirty-eight patients (52%) lived in rural or suburban areas; neither fleabites nor exposure to rats were reported. The most common clinical symptoms were: fever, headache, and myalgia. A maculopapular and non-confluent rash was observed in 47 patients (64.4%). No inoculation eschar was observed in any patient. Eight patients presented with interstitial pneumonia and two with lymphocytic meningitis. The diagnosis was confirmed by indirect fluorescence assay in every case. A single titer of IgM ≥ 128 was found in 62 (84.9%) cases. The other 11 cases were diagnosed by seroconversion. All patients were given antibiotics. Tetracyclines were prescribed in 57 cases (78%). The two patients presenting with meningitis were treated with fluoroquinolone. The outcome was favorable for all patients and no relapse was observed. CONCLUSION: The features of murine typhus are non-specific. The definitive diagnosis is based on serologic testing by indirect fluorescent assay. Cyclins were the most prescribed antibiotics.

Optimal method for collection of umbilical cord blood: an Egyptian trial for a public cord blood bank.

BACKGROUND: Umbilical cord blood (UCB) contains stem cells and can be used as an alternative to bone marrow transplantation. Engraftment is dependent on the total nucleated cell (TNC) and CD34+ cell counts of the cord blood units. This study was designed to evaluate the effect of the method of collection of the UCB on the yield of the cord blood units. STUDY DESIGN AND METHODS: Informed consent was obtained from 100 eligible mothers for donation of cord blood. Both in utero and ex utero methods were used for collection. The cord blood volume was measured. The TNC and the CD34+ cell counts were enumerated. RESULTS: We have found that in utero collection gave significantly larger volumes of cord blood and higher TNC counts than ex utero collection. There was no significant difference between both methods regarding the CD34+ cell counts. This study revealed a significant correlation between the volume of the collected cord blood and both TNC and CD34+ cell counts. CONCLUSION: It is better to collect cord blood in utero before placental delivery to optimize the quality of the cord blood unit.

"Left-sided" Chilaiditi sign? A large gastric perforation with secondary pancreatitis.

BACKGROUND: Although the Chilaiditi sign correctly underestimates the radiological presence of air-under-the-diaphragm, in few cases it has lead to delays in the diagnosis of underlying pneumoperitoneum. In this article we report the case of a young lady presenting with acute pancreatitis and radiographic findings of "left-sided" Chilaiditi sign with underlying a large gastric perforation. CASE REPORT: A 35 year old Caucasian female presented to the Emergency Department with a twenty-four hour history of severe epigastric pain radiating into her back. Stable observations, mildly raised white cell count, increased amylase and subdiaphragmatic radiolucency were interpreted as acute pancreatitis with Chilaiditi sign and treated accordingly. Twenty-four hours later the deterioration of the clinical conditions required a CT scan and an emergency laparotomy that lead to the diagnosis of a large gastric perforation. However, after several days she died of a disseminated intravascular coagulation in the Intensive Care Unit. CONCLUSIONS: In our case the young age of the patient and lack of underlying comorbidities initially compensated the severity of the perforation until it became evident from the absent resolution of the pancreatitis. Bearing this in mind, radiological appearances similar to Chilaiditi sign with significant symptoms or signs should be investigated with a CT scan in order to reach promptly a correct diagnosis.

Prevalence and causes of visual impairment in diabetic patients in Tunisia, North Africa.

PURPOSE: To investigate the prevalence and causes of blindness and partial sight among a population of Tunisian diabetic patients. METHODS: A cross-sectional study of 2320 randomly identified patients with diabetes mellitus. Patient's characteristics as well as data from the last ophthalmic examination were reviewed. RESULTS: Of all patients examined, 60.2% were females and 39.8% were males. Mean age of patients was 54.5 years. Mean duration of diabetes was 7.6 years. Diabetic retinopathy (DR) was recorded in 26.3% of patients, and was proliferative in 3.4% of patients. The prevalence of visual impairment was 22.2%, with 4.4% patients legally blind and 17.8% partially sighted. Visual impairment was significantly associated with age ≥60 years (P<0.001), duration of diabetes >10 years (P<0.001), body mass index >25 (P=0.014), hypertension (P<0.001), heart disease (P<0.001), peripheral neuropathy (P=0.03), vegetative neuropathy (P=0.002), macroalbuminuria (P<0.001), cataract (P<0.001), DR (P<0.001), diabetic macular edema (P<0.001), open angle glaucoma (P<0.001), intravitreal hemorrhage (P<0.001), rubeosis iridis (P<0.001), neovascular glaucoma (P<0.001), and tractional retinal detachment (P<0.001). CONCLUSION: The current report is the largest study of DR in North African region. It provides a baseline data against which future progress can be assessed. Screening and treatment can greatly reduce the incidence of visual impairment due to diabetes.

Goblet cells carcinoid with mucinous adenocarcinoma of the vermiform appendix: a step towards the unitary intestinal stem cell theory?

Associations of various histotypes in appendiceal neoplasms may help elucidate the histogenesis of such uncommon tumors. We present the fourth published case of Goblet Cell Carcinoid (GCC) associated with mucinous adenocarcinoma of the appendix. This association has been described only for GCC and not for classic appendix carcinoids which are thought to originate from neuroendocrine-committed cells. The GCC-mucinous association adds more towards the theory of a pluripotent intestinal stem cell with amphicrine possibilities of differentiation.

[Comparison of the Latissimus dorsi insertions on the iliac crest in chimpanzee (Pan troglodytes) and in man]. / Étude comparative des insertions du Latissimus dorsi sur la crête iliaque chez l'homme et dans le chimpanzé (Pan troglodytes).

INTRODUCTION: Comparing to other primates, one of the most important specificities of the human anatomy are consequences of bipedalism. Although bone consequences are well known (lumbar lordosis, horizontal position of the foramen magnum, lengthening of the lower limbs, reduction of the pelvis, specialization of the foot), consequences of our locomotion on the Latissimus dorsi are still unclear. MATERIALS AND METHODS: One dissection of a chimpanzee Latissimus dorsi (Pan troglodytes) has been performed and compared to 30 human Latissimus dorsi dissections (10 fresh cadavers and 20 formoled cadavers). In each dissection, the existence of direct muscular insertions on the iliac crest has been investigated and the constitution of the thoracolumbar fascia has been described. RESULTS: In chimpanzee dissection, a muscular direct insertion of the Latissimus dorsi was present on the iliac crest of 9 cm long. The TLF was made of the superficial and the deep fascias of the Latissimus dorsi and the superficial fascia of the erector spinae muscles which was deeper. In man, there was no direct muscular insertion of the Latissimus dorsi in 90 % of cases, the TLF was constituted the same way. CONCLUSION: This study suggests that the Latissimus dorsi has been separated from the iliac crest in man during the evolution because of the permanent bipedalism and that it stayed inserted on the iliac crest in chimpanzee because of the brachiation.

Role of CCL18 in asthma and lung immunity.

Allergic asthma is a prototypic Th2 mediated disease, where chemokines orchestrate the inflammatory cell recruitment. Most chemokines have a pro-inflammatory role. In this review, we focus on the potential role, in asthma and lung immunity, of CCL18 a chemokine both constitutively expressed at high levels in the lung and induced in inflammatory conditions. This chemokine is mainly produced by antigen presenting cells, and induced by Th2 type cytokines. The available data suggest that this chemokine may exhibit dual functions, with both pro- and anti-inflammatory properties, the latter through its ability to generate adaptive regulatory T cells in healthy subjects, with a loss of function in allergic patients. However, the functional implications are at the moment hampered by the lack of data on the nature of its putative receptor, and the absence of murine orthologue.