Purpose: Allgrove syndrome, also known as “triple A” syndrome, is characterized by adrenal insufficiency, achalasia, and alacrimia. When neurological signs are also present, the condition is referred to as “4 A” syndrome. Methods: We conducted a retrospective analysis of three patients with 4 A syndrome confirmed genetically. A complete neurological exam was carried out by an experimented neurologist. Results: Herein, we describe the neurological characteristics often associated with this condition, through the clinical and electrophysiological analysis of three patients. All patients exhibited a mutation in AAAS, the gene coding for ALADIN. While these individuals presented with the classic features of triple-A syndrome, neurological symptoms were not prominent. Conclusion The neurological manifestations of Allgrove syndrome have historically been overlooked and inadequately explored. Due to the condition’s rarity and substantial phenotypic heterogeneity, only recently have a variety of symptoms been recognized and described.

Osteogenesis imperfecta (OI) is an inherited skeletal disorder that leads to bone fragility and multiple fractures. Given advances in the genetic understanding of existing phenotypes and newly discovered mutations, therapeutic management of OI has become challenging. Denosumab, a monoclonal antibody that inhibits the interaction between the receptor activator of nuclear factor kappa B ligand (RANKL) and its receptor RANK, has been approved to treat postmenopausal osteoporosis and emerged as an important therapy for malignancies and other skeletal disorders, including pediatric skeletal conditions such as OI. This review summarizes information about denosumab therapy in OI by exploring its mechanisms of action, main indications, and safety and efficacy. Several case reports and small series have been published about the short-term use of denosumab in children with OI. Denosumab was considered a strong drug candidate for OI patients with bone fragility and a high risk of fracture, particularly for patients with the bisphosphonate (BP)-unresponsive OI-VI subtype. The evidence for denosumab's effects in children with OI indicates that it effectively improves bone mineral density but not fracture rates. A decrease in bone resorption markers was observed after each treatment. Safety was assessed by tracking the effects on calcium homeostasis and reporting side effects. No severe adverse effects were reported. Hypercalciuria and moderate hypercalcemia were reported, suggesting that BPs be used to prevent the bone rebound effect. In other words, denosumab can be used as a targeted intervention in children with OI. The posology and administration protocol require more investigation to achieve secure efficiency.

Hypoxia-inducible factor-1 alpha (HIF-1α) is one of the master regulators of immune and metabolic cellular functions. HIF-1α, a transcriptional factor whose activity is closely related to oxygen levels, is a target for understanding infectious disease control. Several studies have demonstrated that HIF-1α plays an important role during the infectious process, while its role in relation to parasite virulence has not been addressed. In this work, we studied the expression levels of HIF-1α and related angiogenic vascular endothelial growth factor A (VEGF-A) in human macrophages infected with promastigotes of hypo- or hyper-virulent Leishmania major human isolates. L. major parasites readily subverted host macrophage functions for their survival and induced local oxygen consumption at the site of infection. In contrast to hypo-virulent parasites that induce high HIF-1α expression levels, hyper-virulent L. major reduced HIF-1α expression in macrophages under normoxic or hypoxic conditions, and consequently impeded the expression of VEGF-A mRNA. HIF-1α may play a key role during control of disease chronicity, severity, or outcome.

Methods: A retrospective study was conducted using the data of all patients hospitalized for TS and BS in the infectious diseases department between 1991 and 2018. Results: Among a total of 117 patients, 73 had TS (62.4%) and 44 had BS (37.6%). Females were significantly more affected with TS than males (56.2% vs. 22.7%, p<0.001). Fever (72.7% vs. 45.2%, p=0.004) and sweating (72.7% vs. 47.9%, p=0.009) were significantly more frequent among patients with BS. The median erythrocyte sedimentation rate was significantly higher in the TS group (median, 70 mm/hr; interquartile range [IQR], 45–103 mm/hr) than in the BS group (median, 50 mm/hr; IQR, 16–75 mm/hr) (p=0.003). Thoracic involvement was significantly more frequent in the TS group (53.4% vs. 34.1%, p=0.04), whereas lumbar involvement was significantly more frequent in the BS group (72.7% vs. 49.3%, p=0.01). Initial imaging findings revealed significantly higher frequencies of posterior vertebral arch involvement, vertebral compaction, and spinal cord compression in the TS group. Percutaneous abscess drainage (20.5% vs. 2.3%, p=0.005) and surgical treatment (17.8% vs. 2.3%, p=0.01) were more frequently indicated in the TS group, with a significant difference. Conclusions A combination of clinical, laboratory, and radiological features can be used to distinguish between TS and BS while these patients await diagnosis confirmation.

Objective: This research was performed to evaluate the effect of tebuconazole (TBZ) on reproductive organs of male rats and to assess the protective role of combined essential trace elements in alleviating the detrimental effect of TBZ on male reproductive function. Methods: For this purpose, 48 rats were exposed to 100 mg/kg TBZ, TBZ supplemented with zinc (Zn), selenium (Se), copper (Cu), and iron (Fe), TBZ + (Se + Zn); TBZ + Cu; or TBZ + Fe. The experiment was conducted for 30 consecutive days. Results: TBZ caused a significant perturbation in mineral levels and reduction in reproductive organs weights, plasma testosterone level, and testicular antioxidant enzyme activities. The TBZ-treated group also showed a significant increase in sperm abnormalities (count, motility, and viability percent), plasma follicle-stimulating hormone and luteinizing hormone concentrations, lipid peroxidation, protein oxidation, and severe DNA degradation in comparison with the controls. Histopathologically, TBZ caused testis impairments. Conversely, treatment with trace elements, in combination or alone, improved the reproductive organ weights, sperm characteristics, TBZ-induced toxicity, and histopathological modifications in testis. Conclusion TBZ exerts significant harmful effects on male reproductive system. The concurrent administration of trace elements reduces testis dysfunction, fertility, and toxicity induced by TBZ.
Animal Feed/analysis* ; Animals ; Antioxidants/metabolism* ; Diet ; Dietary Supplements/analysis* ; Fungicides, Industrial/adverse effects* ; Male ; Minerals/metabolism* ; Mutagenicity Tests ; Rats ; Rats, Wistar ; Spermatozoa/physiology* ; Testis/physiology* ; Trace Elements/metabolism* ; Triazoles/adverse effects*

OBJECTIVETo determine the medicinal potential of various plants and their parts extracted with different solvents.

METHODSThe total phenolic content of acetonitrile/water (60%-40%) (ACN/W) and aqueous (W) extract fractions was determined by high-performance liquid chromatography (HPLC), and terpenic compounds were detected by gas chromatography/mass spectrometry (GC/MS). Antioxidant activity of the samples was evaluated using 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay and β-carotene bleaching method. Cell viability was investigated by thiazolyl blue tetrazolium bromide [3-(4,5-dimethylthiazol)-2-yl 2,5-diphenyltetrazolium bromide] (MTT) assay. The mechanisms involved in cytotoxic activity were investigated in a murine macrophage cell line (RAW 264.7) and cancer lines.

RESULTSOur findings show that 11 plant species exhibited biological activity. In addition, moderate antibacterial activity was reported against one or more of the tested bacterial strains at two concentrations: 300 μg and 3 mg/disc. Furthermore, our data reveal that among all plants investigated, some extract and hydrophobic fractions were potent scavengers of the DPPH radical (6.78 μg/mL < EC50 < 8.55 μg/mL). Taken together, our results show that Nerium oleander (NOACN/W) and Pituranthos tortuosus (PTACN/W) were highly cytotoxic against RAW 264.7 cells with IC80 values of 0.36, and 1.55 μg/mL, respectively. In contrast, murine macrophage cell lines had low growth and were significantly sensitive to water extracts of Thymus hirtus sp. algeriensis (THW), Lavandula multifida (LMW), and ACN/W extract of Erica multiflora (EMACN/W) at doses > 400, 47.20, and 116.74 μg/mL, respectively. The current work demonstrates that RAW 264.7 cell proliferation was inhibited by samples in a dose-dependent manner.

CONCLUSIONOur findings, validated through free radical scavenging activity, agar diffusion assay, and cytotoxicity of essential oils towards cancer cells, show that ethnomedicinal plants used in this work have a novel application as a tumor suppressor.

Animals ; Anti-Bacterial Agents ; chemistry ; pharmacology ; Antineoplastic Agents, Phytogenic ; chemistry ; pharmacology ; Bacteria ; drug effects ; Biphenyl Compounds ; Cell Line ; Cytotoxins ; chemistry ; pharmacology ; Ethnobotany ; Mice ; Molecular Structure ; Phenols ; chemistry ; pharmacology ; Picrates ; Plant Extracts ; chemistry ; pharmacology ; Plants, Medicinal ; chemistry ; Terpenes ; chemistry ; pharmacology ; Tunisia

OBJECTIVEWe evaluate the effects of Thymus algeriensis (TEO) against hydrogen peroxide (H2O2) toxicity on body and testis weight, testis sperm count, testis lipid peroxidation, and antioxidant enzyme activities in rats.

METHODSRats were treated with low (LD) and high dose (HD) of H2O2 (0.1 and 1 mmol/L) in the presence or absence of TEO (150 mg/kg).

RESULTSThe results exhibited a significant decrease in body weight and testis weight, in total sperm number decrease (P<0.05), sperm motility and percentage of sperm viability, leading to complete arrest, in sperm flagellar beat frequency by the gavage of 1 mmol/L H2O2 compared to controls. The administration of H2O2 resulted in a significant reduction in testis GSH, GPx, CAT, SOD, and GST activity and significant increase (P<0.05) in MDA concentration compared with the untreated control animals. TEO pre-treatment protected testis from the H2O2 generated oxidative stress. These results were confirmed by histological architecture examinations.

CONCLUSIONH2O2 has the ability to alter the sperm function, characteristics and development of testis. However, TEO is an efficient natural agent, which can prevent the testis from H2O2-induced oxidative damage in rats.

Animals ; Hydrogen Peroxide ; toxicity ; Male ; Oxidative Stress ; Plant Extracts ; pharmacology ; Rats ; Rats, Wistar ; Testis ; drug effects ; Thymus Plant ; chemistry

The determination of the accurate immune status of pregnant women is crucial in order to prevent congenital toxoplasmosis. Equivocal results with conventional serological techniques are not uncommon when IgG titers are close to the cut-off value of the test, so that a confirmatory technique is needed. For this purpose, we developed a homemade immunoblot (IB) using soluble extract of Toxoplasma gondii tachyzoites and assessed it by testing 154 positive, 100 negative, and 123 equivocal sera obtained from pregnant women. In order to select the more valuable bands in terms of sensitivity and specificity, we used the Youden Index (YI). The highest YIs were those given by the 32, 36, 98, 21, and 33 bands. The simultaneous presence on the same blot of at least 3 bands showed a much higher YI (0.964) and was adapted as the positivity criterion. The analysis of results showed that our homemade IB correlated well with the commercial LDBIO Toxo II IgG(R) kit recently recommended as a confirmatory test (96.7% of concordance).
Female ; Humans ; Immunoenzyme Techniques/*methods ; Immunoglobulin G/*blood/immunology ; Pregnancy ; Reagent Kits, Diagnostic ; Toxoplasmosis/*diagnosis

The performance values of available techniques used in serodiagnosis of toxoplasmosis are satisfactory but they raise problems of equivocal and discordant results for very low IgG titers. Recently marketed, LDBio-Toxo II IgG Western blot (IB) showed an excellent correlation with the dye test. We estimated the proportion of equivocal and discordant results between the enzyme immunoassay Platelia Toxo IgG (EIA-IgG) and fluorescent antibody test (FAT) and assessed the usefulness of the IB as a confirmatory test. Out of 2,136 sera collected from pregnant women, 1,644 (77.0%) tested unequivocally positive and 407 (19.0%) were negative in both EIA-IgG and FAT. The remaining 85 (4%) sera showed equivocal or discordant results. Among them, 73 (85.9%) were positive and 12 (14.1%) were negative in IB. Forty-one (89.1%) equivocal sera in EIA-IgG and 46 (86.8%) equivocal sera in FAT were positive in IB. Reducing the cut-off values of both screening techniques improved significantly their sensitivity in detecting very low IgG titers at the expense of their specificity. In conclusion, equivocal results in routine-used techniques and their discordance in determination of the immune status in pregnancy women were not uncommon. IB test appeard to be highly useful in these situations as a confirmatory technique.
Adult ; Antibodies, Protozoan/*analysis/blood ; Blotting, Western/*methods ; Female ; Fluorescent Antibody Technique/*methods ; Humans ; Immunoenzyme Techniques/*methods ; Immunoglobulin M/*analysis/blood ; Pregnancy ; Pregnancy Complications, Parasitic/blood/*diagnosis ; Toxoplasmosis/blood/*diagnosis ; Young Adult

In vitro supplementation with date seed oil (DSO) can protect spermatozoa against hydrogen peroxide (H2O2)-mediated damage and can improve sperm function, possibly owing to antioxidant properties. We tested the antioxidant effects of DSO on human sperm motility, sperm viability, reacted acrosome and lipid peroxidation assessed in vitro after H2O2-mediated oxidative damage in spermatozoa. Sixteen patients (mean age: 35 years; range: 25-45 years) referred to the Histology-Embryology Laboratory of the Medicine Faculty of Sfax for semen analysis after 12-24 months of sexual intercourse without conception were selected. After spermiogram, sperm selection by two-interface discontinuous Sill Select gradient was performed, and selected spermatozoa were used in four experimental assays: control; incubation with 100 microm H2O2; incubation with 0.1% DSO; and co-incubation with 0.1% DSO and 100 microm H2O2. Motility and viability were determined using World Health Organization criteria. Acrosome reaction and lipid peroxidation were assessed by staining with fluorescein isothiocyanate-Pisum sativum and spectrophotometric measurement of malondialdehyde, respectively. Results showed that incubation with H2O2 alone led to a significant increase in lipid peroxidation (57.83%, P<0.05) associated with a significant decrease in sperm motility, sperm viability (after 30 min and 24 h) and percentage of reacted acrosome (P<0.05). Date seed oil improved sperm motility after 24 h of incubation (P<0.05) and protected spermatozoa against the deleterious effects of H2O2 on motility, viability, acrosome reaction and lipid peroxidation. We conclude that supplementation with DSO may have a function in antioxidant protection against male infertility.
Acrosome Reaction ; drug effects ; Adult ; Arecaceae ; Cell Survival ; drug effects ; Humans ; Hydrogen Peroxide ; pharmacology ; In Vitro Techniques ; Lipid Peroxidation ; drug effects ; Male ; Middle Aged ; Oxidants ; pharmacology ; Oxidative Stress ; drug effects ; Plant Oils ; pharmacology ; Seeds ; Sperm Motility ; drug effects ; Spermatozoa ; cytology ; drug effects ; metabolism