Plasmodium falciparum alters the trophoblastic barrier and stroma villi organization of human placental villi explants.

BACKGROUND: The sequestration of Plasmodium falciparum infected erythrocytes in the placenta, and the resulting inflammatory response affects maternal and child health. Despite existing information, little is known about the direct impact of P. falciparum on the placental barrier formed by trophoblast and villous stroma. This study aimed to assess placental tissue damage caused by P. falciparum in human placental explants (HPEs). METHODS: HPEs from chorionic villi obtained of human term placentas (n = 9) from normal pregnancies were exposed to P. falciparum-infected erythrocytes (IE) for 24 h. HPEs were embedded in paraffin blocks and used to study tissue damage through histopathological and histochemical analysis and apoptosis using TUNEL staining. Culture supernatants were collected to measure cytokine and angiogenic factors and to determine LDH activity as a marker of cytotoxicity. A subset of archived human term placenta paraffin-embedded blocks from pregnant women with malaria were used to confirm ex vivo findings. RESULTS: Plasmodium falciparum-IE significantly damages the trophoblast layer and the villous stroma of the chorionic villi. The increased LDH activity and pathological findings such as syncytial knots, fibrin deposits, infarction, trophoblast detachment, and collagen disorganization supported these findings. The specific damage to the trophoblast and the thickening of the subjacent basal lamina were more pronounced in the ex vivo infection. In contrast, apoptosis was higher in the in vivo infection. This disparity could be attributed to the duration of exposure to the infection, which significantly varied between individuals naturally exposed over time and the 24-h exposure in the ex vivo HPE model. CONCLUSION: Exposure to P. falciparum-IE induces a detachment of the syncytiotrophoblast, disorganization of the stroma villi, and an increase in apoptosis, alterations that may be associated with adverse results such as intrauterine growth restriction and low birth weight.

A gain-of-function mutation in TRPA1 causes familial episodic pain syndrome.

Human monogenic pain syndromes have provided important insights into the molecular mechanisms that underlie normal and pathological pain states. We describe an autosomal-dominant familial episodic pain syndrome characterized by episodes of debilitating upper body pain, triggered by fasting and physical stress. Linkage and haplotype analysis mapped this phenotype to a 25 cM region on chromosome 8q12-8q13. Candidate gene sequencing identified a point mutation (N855S) in the S4 transmembrane segment of TRPA1, a key sensor for environmental irritants. The mutant channel showed a normal pharmacological profile but altered biophysical properties, with a 5-fold increase in inward current on activation at normal resting potentials. Quantitative sensory testing demonstrated normal baseline sensory thresholds but an enhanced secondary hyperalgesia to punctate stimuli on treatment with mustard oil. TRPA1 antagonists inhibit the mutant channel, promising a useful therapy for this disorder. Our findings provide evidence that variation in the TRPA1 gene can alter pain perception in humans.

[Biopercular syndrome caused by unilateral ischemia. Report of one case]. / Síndrome biopercular producido por lesión unilateral.

Biopercular syndrome is a labio-facio-pharyngeal-laryngeal-gloso-masticatory diplegia, with automatic dissociation of movements. Ischemia is the most common etiology when it occurs bilaterally in the opercular area, but it has been also described in patients with bilateral subcortical lesions. There are few cases described with unilateral lesions. We report a 76-year-old woman who developed a biopercular syndrome caused by unilateral ischemic lesion of the right middle cerebral artery confirmed by magnetic resonance imaging and cerebral SPECT.

Síndrome biopercular producido por lesión unilateral / Biopercular syndrome caused by unilateral ischemia: report of one case

Biopercular syndrome is a labio-facio-pharyngeal-laryngeal-gloso-masticatory diplegia, with automatic dissociation of movements. Ischemia is the most common etiology when it occurs bilaterally in the opercular area, but it has been also described in patients with bilateral subcortical lesions. There arefew cases described with unilateral lesions. We report a 76-year-old woman who developed a biopercular syndrome caused by unilateral ischemic lesion ofthe right middle cerebral artery confirmed by magnetic resonance imaging and cerebral SPECT.