Voluptuary habits and clinical subtypes of Parkinson's disease: The FRAGAMP case–control study

We evaluated the possible association between smoking, coffee drinking, and alcohol consumption and Parkinson's disease (PD). The FRAGAMP study is a large Italian multicenter case–control study carried out to evaluate the possible role of environmental and genetic factors in PD. Adjusted ORs were estimated using unconditional logistic regression. Smoking, coffee, and alcohol consumption were also considered as surrogate markers of lifestyle and analysis was carried out considering the presence of at least one, two, or three factors. This latter analysis was separately performed considering Tremor‐Dominant (TD) and Akinetic‐Rigid (AR) patients. Four hundred ninety‐two PD patients (292 men and 200 women) and 459 controls (160 men and 299 women) were enrolled in the study. Multivariate analysis showed a significant negative association between PD and cigarette smoking (OR 0.51; 95%CI 0.36–0.72), coffee drinking (OR 0.61; 95%CI 0.43–0.87) and wine consumption (OR 0.62; 95%CI 0.44–0.86); a significant trend dose‐effect (P < 0.05) has been found for all the factors studied. We have also found a trend dose‐effect for the presence of at least one, two or three factors with a greater risk reduction (83%) for the presence of three factors. However, a different strength of association between TD and AR was found with a greater risk reduction for the AR patients. We found a significant inverse association between PD smoking, coffee, and alcohol consumption. When analysis was carried out considering the association of these factors as possible surrogate markers of a peculiar lifestyle the association was stronger for the AR phenotype. © 2010 Movement Disorder Society.     

Foot pad skin biopsy in mouse models of hereditary neuropathy

Numerous transgenic and knockout mouse models of human hereditary neuropathies have become available over the past decade. We describe a simple, reproducible, and safe biopsy of mouse skin for histopathological evaluation of the peripheral nervous system (PNS) in models of hereditary neuropathies. We compared the diagnostic outcome between sciatic nerve and dermal nerves found in skin biopsy (SB) from the hind foot. A total of five animal models of different Charcot-Marie-Tooth neuropathies, and one model of congenital muscular dystrophy associated neuropathy were examined. In wild type mice, dermal nerve fibers were readily identified by immunohistochemistry, light, and electron microscopy and they appeared similar to myelinated fibers in sciatic nerve. In mutant mice, SB manifested myelin abnormalities similar to those observed in sciatic nerves, including hypomyelination, onion bulbs, myelin outfolding, redundant loops, and tomacula. In many strains, however, SB showed additional abnormalities--fiber loss, dense neurofilament packing with lower phosphorylation status, and axonal degeneration-undetected in sciatic nerve, possibly because SB samples distal nerves. SB, a reliable technique to investigate peripheral neuropathies in human beings, is also useful to investigate animal models of hereditary neuropathies. Our data indicate that SB may reveal distal axonal pathology in mouse models and permits sequential follow-up of the neuropathy in an individual mouse, thereby reducing the number of mice necessary to document pathology of the PNS.     

Abnormal activity of the Na/Ca exchanger enhances glutamate transmission in experimental autoimmune encephalomyelitis

It is increasingly accepted that excessive glutamate release plays a key role in the pathophysiology of grey matter damage in multiple sclerosis (MS). The mechanisms causing abnormal glutamate transmission in this disorder are however largely unexplored. By means of electrophysiological recordings from single striatal neurons in slices, we found that the presymptomatic and acute phases of experimental autoimmune encephalomyelitis (EAE), a preclinical model of MS, are associated with enhanced synaptic release of glutamate. The reverse mode of action of axonal Na⁺/Ca⁺⁺ exchanger, secondary to abnormal functioning of voltage-dependent Na⁺ channels, was identified as a major cause of this alteration. In fact, inhibition of the Na⁺/Ca⁺⁺ exchanger with bepridil or with KB-R7943, which selectively blocks the reverse mode of the exchanger, reduced the frequency of spontaneous excitatory postsynaptic currents (sEPSCs) recorded from striatal neurons in EAE mice but not in control animals. In the presence of tetrodotoxin (TTX), a blocker of voltage-dependent Na⁺ channels, the effect of bepridil was normalized in acute (25 days post-immunization) EAE mice, indicating that axonal accumulation of Na⁺ ions flowing through voltage-dependent Na⁺ channels plays a role in the abnormal activity of the Na⁺/Ca⁺⁺ exchanger in EAE.Our data reveal an important role of Na⁺/Ca⁺⁺ exchanger and of voltage-dependent Na⁺ channels in the pathological process of EAE, and provide a rationale for the use of neuroprotective strategies since the very early stages of MS.     

Leukocyte and cardiac phosphoinositide 3-kinase γ activity in pressure overload-induced cardiac failure

Class IB phosphoinositide 3-kinase p110γ is a master regulator of both leukocyte and cardiomyocyte function. Whereas in the immune system p110γ is principally involved in the control of leukocyte chemotaxis and inflammatory reactions, in cardiomyocytes p110γ affects multiple aspects of β-adrenergic receptor signaling and cardiac function. Because inflammatory cell recruitment/activation and cardiac dysfunction are strictly connected, p110γ has recently been revealed as a promising target for drug design in the treatment of heart failure. This review discusses recent works that dissect the relative contribution of leukocyte p110γ and its cardiac counterpart in the onset and progression of pressure overload-induced cardiac remodeling and the ensuing therapeutic implications.     

Vitamin D receptor (VDR) gene polymorphism is associated with left ventricular (LV) mass and predicts left ventricular hypertrophy (LVH) progression in end‐stage renal disease (ESRD) patients

Left ventricular hypertrophy (LVH) is a strong cardiovascular risk marker in end‐stage renal disease (ESRD) patients. Vitamin D deficiency and/or disturbed vitamin D signaling has been implicated in LVH in experimental models. Because the BsmI vitamin D receptor VDR gene polymorphism may alter VDR function, we performed a cross‐sectional and longitudinal study in a cohort of 182 dialysis patients to investigate (1) the relationship between BsmI VDR gene polymorphism and left ventricular mass index (LVMI) measured by echocardiography and (2) the predictive power of this polymorphism for progression in LVH over a 18 ± 2 months of follow‐up. As a reference group, we used 175 healthy subjects matched to the study population as for age and sex. The distribution of BsmI genotypes did not significantly deviate from Hardy‐Weinberg equilibrium either in patients or in the control group of healthy subjects. The frequency of the B allele of BsmI polymorphism (40.4%) in dialysis patients was similar to that of healthy control subjects (38.6%), and the number of B alleles was directly related to LVMI (r = 0.20, P = .007). This relationship remained robust (β = 0.19, P = .006) in multivariate analysis adjusting for traditional and nontraditional risk factors and antihypertensive and calcitriol treatment. In the longitudinal study, LVMI rose from 60.1 ± 17.9 to 64.2 ± 19.3 g/m^2.7 (P < .001), and again, the number of B alleles was associated with LVMI changes both in crude and in fully adjusted analyses. These cross‐sectional and longitudinal observations coherently support the hypothesis that altered vitamin D signaling is implicated in LVH in ESRD patients. © 2010 American Society for Bone and Mineral Research     

Early appearance of hypokalemia in Gitelman syndrome

Inactivating mutations in the SLC12A3 gene that encodes the thiazide-sensitive co-transporter causes Gitelman syndrome. The main features of this syndrome include normal or low blood pressure, hypokalemia, metabolic alkalosis, hypomagnesemia, hypocalciuria, and hyperreninemia. These patients are at low risk for preterm birth and do not present with symptoms before school age. As a consequence, the condition is usually diagnosed in late childhood or in adult life. We report on four patients, two pairs of prematurely born twins, in whom hypokalemia was demonstrated early in life. In these children, a tendency towards hypokalemia was first noted during the third week of life. Overt hypokalemia subsequently appeared associated with normal blood pressure, hypochloremia, hyperreninemia, and an inappropriately high fractional excretion of potassium and chloride. Molecular biology studies failed to detect mutations in the SLC12A1, KCNJ1, and CLCNKB genes responsible for the Bartter syndromes type I, II and III, respectively. Compound heterozygous mutations in the SLC12A3 gene were detected in both pairs of twins: a frameshift mutation in exon 10 (c.1196_1202dup7bp), leading to the truncated protein p.Ser402X, and a missense mutation in exon 11, p.Ser475Cys (c.1424C>G) in the first pair; two missense mutations, p.Thr392Ile (c.1175C>T) in exon 9 and p.Ser615Leu in exon 15 (c.1844C>T), in the second pair. In conclusion, the diagnosis of Gitelman syndrome deserves consideration in infants with unexplained hypokalemia.     

Treatment of Frey's syndrome with botulinum toxin type B

Objective

Frey's syndrome is a frequent sequela of parotidectomy, causing facial sweating and flushing because of gustatory stimuli. Although botulinum toxin type A has become first-line therapy for Frey's syndrome, some patients become resistant. In this study, we investigated whether another serotype, botulinum toxin type B, might be an effective alternative.

Study Design

Case series with planned data collection.

Setting

Otolaryngology department in a university hospital.

Subjects and Methods

Seven patients aged 30 to 68 years, with severe Frey's syndrome, underwent the Minor test and had 80 U of botulinum toxin type B per cm² (mean total dose, 2354 U) injected intracutaneously in the mapped area of gustatory sweating. All patients were followed up for 12 months.

Results

One month after treatment, six of the seven patients reported that gustatory sweating and flushing had resolved, and, in the remaining patient, these symptoms had decreased. The Minor test confirmed a significant improvement. The subjective benefits remained stable for six months in four patients and for nine months in the remaining three patients; 12 months after treatment, all patients still reported some improvement.

Conclusion

Botulinum toxin type B afforded symptomatic relief in a small sample of patients with Frey's syndrome and might be considered a potential alternative to botulinum toxin type A.