Human lissencephaly with cerebellar hypoplasia due to mutations in TUBA1A: expansion of the foetal neuropathological phenotype

Neuronal migration disorders account for a substantial number of cortical malformations, the most severe forms being represented by lissencephalies. Classical lissencephaly has been shown to result from mutations in LIS1 (PAFAH1B1; MIM#601545), DCX (Doublecortin; MIM#300121), ARX (Aristaless-related homeobox gene; MIM#300382), RELN (Reelin; MIM#600514) and VLDLR (Very low density lipoprotein receptor; MIM#224050). More recently, de novo missense mutations in the alpha-tubulin 1a gene (TUBA1A) located on chromosome 12q13.12, have also been associated with more or less severe defects of cortical development, resulting in complete agyria in the most severe cases of lissencephaly. We report here the cerebral lesions in a 36 weeks’ gestation female foetus with a novel de novo missense mutation in the TUBA1A gene, presenting the most severe antenatal phenotype reported so far. Using routine immunohistochemistry and confocal microscopy, we show evidence for defects in axonal transport in addition to defects in neuronal migration and differentiation, giving new insights to the pathophysiology of this form of lissencephaly.     

Squamous cell carcinoma arising in Verneuil's disease

BACKGROUND: Verneuil's disease or hidradenitis suppurativa is a chronic suppurative, and cicatricial inflammatory disease, mainly affecting apocrine-bearing area of the skin. Squamous cell carcinoma is an uncommon but a frightening complication of hidradenitis suppurativa. AIM: To report a new case of squamous cell carcinoma arising in Verneuil's disease. CASE REPORT: We reported a case of 60 year old man with a 30 years history of hidradenitis suppurativa in which squamous cell carcinoma arise. A wide surgical excision removing the tumour and leaving a large defect was performed. The patient had a well recovery, wounds healed well by primary intention. No recurrence observed at 18 months of follow up. CONCLUSION: Squamous cell carcinoma is an uncommon complication of hidradenitis suppurativa. Surgical excision represents also the treatment of choice.     

Bcl-2 expression and triple negative profile in breast carcinoma

Appearance of non-Hodgkin’s lymphomas (NHL) and renal cell carcinoma (RCC) in same person has been reported in the literature. There is a higher-than-expected incidence of co-occurrence of these neoplastic disorders. The cause for this association remains speculative. Two epidemiological studies have shown that the observed-to-expected ratio for occurrence of RCC in NHL patients were 1.86 to 2.67. We herein describe five patients with both RCC and lymphoid malignancies, and reviewed possible explanations for the association. In three of the five patients, RCC was diagnosed during lymphoproliferative disease work-up, and remaining two cases had been diagnosed with chronic lymphocytic leukemia 1 and 5 years prior to RCC. All RCC cases were detected during staging of the primary tumor, usually by CT scan and/or ultrasound. Our data are in correlation with the literature that there is an increased association of RCC and NHL more often among male patients, and that the lymphoproliferative disease often presents with extranodal involvement. The specialists should be alerted for this possibility when evaluating patients at diagnosis or during follow-up.     

The role of ARX in cortical development

The ARX protein (encoded by the aristaless-related homeobox gene) is a member of the paired class of homeoproteins. More precisely, it is a member of the Aristaless subclass of proteins with a glutamine residue (Q) at the critical position 50 of the homeodomain (Q50). Through identification of diverse inherited or de novo mutations, genetic investigations of X-linked mental retardation conditions have demonstrated the implication of ARX in a wide spectrum of disorders extending from phenotypes with severe neuronal migration defects, such as lissencephaly, to mild forms of X-linked mental retardation without apparent brain abnormalities. These investigations have recently directed attention to the role of this gene in brain development. Analysis of its spatiotemporal localization profile have revealed expression mainly in telencephalic structures at all stages of development. Interestingly, in adult, ARX expression becomes restricted to a population of GABAergic neurons. Although the identification of the target genes regulated by ARX remains a crucial step to better understanding its role during brain development, studies of the role of ARX orthologs in different models have indicated that it is essential for important developmental processes such as proliferation, cell differentiation and neuronal migration.     

Molluscicidal activity of Solanum elaeagnifolium seeds against Galba truncatula intermediate host of Fasciola hepatica: Identification of β-solamarine

Context: The persistence of fascioliasis in many developing countries urges the search for simple, cheap, and effective substances. In this view, plants provide interesting molluscicidal activities thanks to the secondary metabolites they produce. The genus Solanum is known for its potent effect on vector snails.

Objective: The molluscicidal activity of Solanum elaeagnifolium Cav. (Solanaceae) seeds against Galba truncatula Müll. (Lymnaeidae), intermediate host of Fasciola hepatica L. (Fasciolidae), was evaluated.

Materials and methods: Solanum elaeagnifolium seeds were powdered and successively extracted using n-hexane, methylene chloride, acetone, and methanol, for 20?h each. After filtration, solvents were evaporated. An acid–base treatment was conducted on seed methanolic extract to isolate total alkaloids and β-solamarine. Total saponins fraction was obtained after successive macerations and evaporations. The molluscicidal activity was evaluated by subjecting snails, in groups of 10, for 48?h to 500?mL of extracts, fractions, and pure product aqueous solutions, each containing amounts, ranging from 1 to 50?mg of plant material in 5?mg increments.

Results: The methanolic extract of seeds, β-solamarine isolated for the first time from this plant and total saponins fraction showed very potent activities on snails, giving respective median lethal concentrations (LC₅₀) of 1.18, 0.49, and 0.94?mg/L. Total alkaloids fraction obtained from the methanolic extract was less active giving an LC₅₀ value of 14.67?mg/L.

Discussion and conclusion: This study emphasizes that glycoalkaloids and saponins of Solanum elaeagnifolium are potent molluscicidal agents. Seed methanolic extract, β-solamarine, and total saponins fraction may be used as molluscicides.     

Antidiarrheal and antioxidant activities of chamomile (Matricaria recutita L.) decoction extract in rats

Ethnopharmacological relevance

Matricaria recutita L. (Chamomile) has been widely used in the Tunisian traditional medicine for the treatment of digestive system disorders. The present work aims to investigate the protective effects of chamomile decoction extract (CDE) against castor oil-induced diarrhea and oxidative stress in rats.

Methods

The antidiarrheal activity was evaluated using castor oil-induced diarrhea method. In this respect, rats were divided into six groups: Control, Castor oil, Castor oil+Loperamide (LOP) and Castor oil+various doses of CDE. Animals were per orally (p.o.) pre-treated with CDE during 1 h and intoxicated for 2 or 4 h by acute oral administration of castor oil.

Results

Our results showed that CDE produced a significant dose-dependent protection against castor oil-induced diarrhea and intestinal fluid accumulation. On the other hand, we showed that diarrhea was accompagned by an oxidative stress status assessed by an increase of malondialdehyde (MDA) level and depletion of antioxidant enzyme activities as superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx). Castor oil also increased gastric and intestinal mucosa hydrogen peroxide (H₂O₂) and free iron levels. Importantly, we showed that chamomile pre-treatment abrogated all these biochemical alterations.

Conclusion

These findings suggested that chamomile extract had a potent antidiarrheal and antioxidant properties in rats confirming their use in traditional medicine.