Hypohidrosis during topiramate treatment: a rare and reversible side effect

Topiramate is an antiepileptic drug with a beneficial clinical effect on various seizure types. Topiramate does not seem to be associated with serious adverse effects and is also well tolerated in pediatric patients. Only few cases of hypohidrosis have been described. This report presents one young patient with complex partial seizures who was medicated with topiramate when she developed fatigue, headache, intermittent hyperthermia, inability to produce sweat secretion, and dryness of the skin. Reduced sweat response was determined using the Wescor Macroduct collection procedure. Topiramate was discontinued, and within 3 weeks a repeat sweat test was completely normal. At that time, clinical signs had also disappeared. Hypohidrosis is an uncommon and reversible side effect reported in association with topiramate therapy. It is rare in patients on monotherapy. Although a definite causal relationship still needs to be established, this side effect might be attributed to an autonomic dysfunction by inhibition of isoenzymes of carbonic anhydrase localized in human eccrine sweat glands.     

Long-term incubation with β-amyloid peptides impairs endothelium-dependent vasodilatation in isolated rat basilar artery

Alzheimer's disease is associated to a cerebral amyloid angiopathy with dysregulation of cerebral blood flow (CBF). In vitro studies have shown that short-term application of β-amyloid (Aβ) peptides to isolated vessels affects vascular tone within 1 h, but no studies have examined the effect of long-term incubation with Aβ. Here we evaluate the effect of Aβ_(1–40) and Aβ_(25–35) in rat basilar artery for up to 24 h. Basilar artery segments were incubated with 25 μM Aβ_(1–40) or Aβ_(25–35), for 6 or 24 h. After treatment, arteries were mounted in a wire myograph, in physiological salt solution gassed with O₂/CO₂, in the absence of Aβ, and challenged with vasoconstrictors and vasodilators. Vasomotor responses were not significantly changed by 6 h treatment with Aβ peptides whereas 24 h treatment with either Aβ_(25–35) or Aβ_(1–40) increased vasoconstriction to 5-hydroxytryptamine (5-HT) and reduced endothelium-dependent vasodilatation to acetylcholine (ACh). Analysis of endothelial cells did not show apoptotic changes associated to endothelial dysfunction, as assessed by TUNEL immunostaining and examination of nuclear morphology, but basal phosphorylation of endothelial nitric oxide synthase (at serine 1177) appeared reduced.These data suggest that long incubation with Aβ peptides induces an alteration of endothelial function in isolated basilar artery, involving eNOS activity without changing cell morphology. This endothelial dysfunction may play a role in the pathogenesis of CBF dysregulation occurring in cerebral amyloid angiopathy and Alzheimer's disease.     

The early course of affective and cognitive symptoms in de novo patients with Parkinson’s disease

Neuropsychiatric and cognitive symptoms are common in patients with Parkinson’s disease (PD) from the early stage of the disease but their course is still unclear. In this study we investigated prospectively the progression of affective and cognitive symptoms and disorders in de novo idiopathic PD patients. Twenty-four de novo drug naïve PD patients underwent a comprehensive neurological, psychopathological and neuropsychological evaluation at the first diagnostic visit (OFF), after 4?6 months when the antiparkinsonian therapy regimen was stabilized (ON-1), and at one year following the ON-1 follow-up visit (ON-2). Generalized least squares analysis revealed a significant improvement over time in the depressive mood, short and long term episodic verbal memory, visual memory, and the motor symptoms. Pairwise comparisons showed a significant change from OFF to ON-1 for all the aforementioned variables, except for short term episodic verbal memory which approached significance. A significant improvement from ON-1 to ON-2, however, was shown for short term episodic verbal memory. An ancillary analysis indicated that overall level and change in a number of cognitive variables, but not depression, was conditional upon age of onset, education, and sometime gender. In conclusion, early stage PD is not associated with affective and cognitive deterioration. On the contrary, very specific neuropsychiatric and cognitive symptoms may improve. This study provides Class III evidence that antiparkinsonian treatment commonly used in the clinical practice improves memory performance and depression severity in de novo patients with PD.     

Emerging therapeutic targets and strategies in Crohn’s disease

Crohn’s disease (CD) is an immune-mediated inflammatory bowel disease, in which inflammation is driven by a complex interaction between the microbiota, immune cells, genes and mediators. New mechanisms of action and several cytokines have been identified as factors involved in the inflammatory process in CD, and many new molecules have been developed to treat this complex disease. New agents have been developed that target leukocyte trafficking, block or adhesion molecules for example, as well as the development of antibodies against classic inflammatory cytokines or therapies directed against IL-12/23 and Janus kinases. The development of selective mechanisms of action and targeting of different cytokines or inflammatory mediators for each patient presents the biggest challenge for the future in CD therapy. Such agents are currently at different phases of development. We aim to review the current literature data on a targeted approach in CD, which could be promising alternative approach for CD patients in the near future.     

Chemical composition modulates the adverse effects of particles on the mucociliary epithelium

OBJECTIVE:We compared the adverse effects of two types of real ambient particles; i.e., total suspended particles from an electrostatic precipitator of a steel mill and fine air particles from an urban ambient particulate matter of 2.5 µm, on mucociliary clearance.METHOD:Mucociliary function was quantified by mucociliary transport, ciliary beating frequency and the amount of acid and neutral mucous in epithelial cells through morphometry of frog palate preparations. The palates were immersed in one of the following solutions: total suspended particles (0.1 mg/mL), particulate matter 2.5 µm 0.1 mg/mL (PM0.1) or 3.0 mg/mL (PM3.0) and amphibian Ringer''s solution (control). Particle chemical compositions were determined by X-ray fluorescence and gas chromatography/mass spectrometry.RESULTS:Exposure to total suspended particles and PM3.0 decreased mucociliary transport. Ciliary beating frequency was diminished by total suspended particles at all times during exposure, while particulate matter of 2.5 µm did not elicit changes. Particulate matter of 2.5 µm reduced epithelial mucous and epithelium thickness, while total suspended particles behaved similarly to the control group. Total suspended particles exhibited a predominance of Fe and no organic compounds, while the particulate matter 2.5 µm contained predominant amounts of S, Fe, Si and, to a lesser extent, Cu, Ni, V, Zn and organic compounds.CONCLUSION:Our results showed that different compositions of particles induced different airway epithelial responses, emphasizing that knowledge of their individual characteristics may help to establish policies aimed at controlling air pollution.     

Cartilage differentiation in ependymoma: histogenetic considerations on a new case

The presence of cartilage in gliomas is a very unusual finding and has been mainly reported in ependymomas and in astrocytomas. A derivation of cartilage from neuroepithelial cells through a neuroepithelial-mesenchymal transition or directly from blood vessel-associated multipotent stromal elements has been proposed. We herein describe a further case of ependymoma with the presence of cartilage in a child affected by a tumor in the posterior fossa. In this case, only the last recurrence, characterized by focal areas of anaplasia, contained a nodule of cartilage. The immunohistochemical expression of fibronectin, tenascin-C, and CD44 was investigated, and the possible role of these molecules in the process of cartilage formation is discussed. Moreover, the literature on the subject is reviewed.