Abnormal gut motility in inflammatory bowel disease: an update.

BACKGROUND: There is substantial evidence linking disturbed gastrointestinal motility to inflammation. Thus, it is not surprising that abnormalities of gastrointestinal motility play a role in inflammatory bowel disease (IBD), affecting patient outcomes. We performed a review of the literature to investigate the relationship between abnormal gut motility and IBD. METHODS: With an extensive literature search, we retrieved the pertinent articles linking disturbed gut motility to IBD in various anatomical districts. RESULTS: The evidence in the literature suggests that abnormal gastrointestinal motility plays a role in the clinical setting of IBD and may confuse the clinical picture. CONCLUSIONS: Abnormal gut motility may be important in the clinical setting of IBD. However, additional data obtained with modern techniques (e.g., magnetic resonance imaging) are needed to individuate in a more precise manner gastrointestinal motor dysfunctions, to understand the nature of clinical manifestations and properly tailor the treatment of patients.

Comparison of brainstem reflex recordings and evoked potentials with clinical and MRI data to assess brainstem dysfunction in multiple sclerosis: a short-term follow-up.

Brainstem dysfunctions are associated to high risk of developing severe disability in patients with multiple sclerosis (PwMS), often undetected by conventional routine assessments. In this view, the purpose of this study was to monitor brainstem function over a short-term period in PwMS, comparing clinical and magnetic resonance imaging (MRI) examinations with evoked potentials (EPs) and brainstem reflexes (BSRs). Forty-five PwMS were evaluated at baseline and after 15.1 ± 4.2 months through Expanded Disability Status Scale (EDSS) score, MRI, EPs, vestibulo-masseteric (VMR), acoustic-masseteric (AMR), vestibulo-collic (VCR) and trigemino-collic (TCR) reflexes. At baseline, brainstem alterations were detected by EDSS, MRI, EPs and BSRs in 40, 77.8, 84.4 and 82.2 % of patients, respectively. At follow-up, EDSS and MRI remained unchanged, while EP and BSR deteriorated in 86.7 and 91.1 % of patients, respectively. Changes from 1 to 3 altered EPs and from 1 to 4 altered BSRs were significant only for EPs (p = 0.028). The analysis of grading severity for each test disclosed significant worsening of the VMR, AMR, TCR and P14 wave of the median somatosensory EP. Combined EP/BSR recordings were significantly more sensitive than paired EDSS/MRI assessments at baseline (93.3 versus 80 %; p = 0.006) and follow-up (97.8 versus 82.2 %; p = 0.008). In the short-term VMR, AMR, TCR and P14 wave disclosed a significant functional brainstem deterioration by detecting lesions that remained clinically and MRI silent. Our findings provide evidence for a valuable role of neurophysiological methods, especially BSRs, in investigating and monitoring brainstem dysfunctions in MS, in comparison with the standard clinical and MRI procedures.

Risk factors associated with colonic diverticulosis among patients from a defined geographic area.

BACKGROUND: Only a few data regarding colonic diverticulosis are available in Italy. We examined the frequency of colonic diverticulosis and its associations with risk factors in a homogeneous Northern Sardinian population undergoing colonoscopy for any reason in the last decades. METHODS: This was a retrospective single-center study. Medical records of patients undergoing colonoscopy for any indication between 1995 and 2013 were reviewed. Demographic information including age, gender, geographic area (urban, rural), marital status, smoking habit, occupation, body mass index, and comorbidities were collected. Presence, number, and extension of diverticula were assessed by colonoscopy. The diagnosis of diverticulosis was defined by the presence of more than five diverticula. RESULTS: A total of 4458 records were collected (39.8 % males). Analysis by birth cohorts showed a significant progressive age-related increase in the prevalence of diverticulosis. The average prevalence was 18.9 % without significant variation across the 19-year observation period. In 101 (12.1 %) subjects diverticula were single or few. Seventy-one percent of diverticula were located predominantly in the left side, 2 % in the right side, and 14.3 % were spread throughout the colon. There was a significant association with obesity but not with smoking habits, marital status, or urban versus rural environment. A strong association was observed between the presence of diverticulosis and cardiovascular and other gastrointestinal and lung disease (p < 0.0001). These associations were also confirmed by the logistic regression analysis. CONCLUSIONS: In this endoscopic study, colonic diverticulosis in Northern Sardinia showed prevalence similar to other series in Western countries, and it was predominantly left sided and age related.

Lifestyle and nutrition related to male longevity in Sardinia: an ecological study.

BACKGROUND AND AIMS: A demographic analysis in the Mediterranean island of Sardinia revealed marked differences in extreme longevity across the 377 municipalities and particularly identified a mountain inner area where the proportion of oldest subjects among male population has one of the highest validated value worldwide. The cause(s) of this unequal distribution of male longevity may be attributed to a concurrence of environmental, lifestyle and genetic factors. METHODS AND RESULTS: In this study we focussed on some lifestyle and nutrition variables recorded in the island's population in early decades of 20th century, when agricultural and pastoral economy was still prevalent, and try to verify through ecological spatial models if they may account for the variability in male longevity. By computing the Extreme Longevity Index (the proportion of newborns in a given municipality who reach age 100) the island's territory was divided in two areas with relatively higher and lower level of population longevity. Most nutritional variables do not show any significant difference between these two areas whereas a significant difference was found with respect to pastoralism (P = 0.0001), physical activity estimated by the average slope of the territory in each municipality (P = 0.0001), and average daily distance required by the active population to reach the usual workplace (P = 0.0001). CONCLUSION: Overall, these findings suggest that factors affecting the average energy expenditure of male population such as occupational activity and geographic characteristics of the area where the population mainly resides, are important in explaining the spatial variation of Sardinian extreme longevity.

Different antioxidant profiles in Italian centenarians: the Sardinian peculiarity.

In this study, 153 Italian centenarians from four different geographical areas, including Modena (northern Italy), Ancona (central Italy), Perugia (central Italy) and Sardinia island (AKEA Project) were enrolled. Plasma levels of vitamin C, uric acid, vitamin A and vitamin E as well as the activities of superoxide dismutase and glutathione peroxidase were measured. Subjects were compared to a younger control population of the same areas, divided into three age groups:

[Latent autoimmune diabetes in adults]. / II diabete autoimmune latente dell'adulto (LADA).

Latent autoimmune diabetes in adults (LADA) is a disorder with onset after age 30, insulin independence for at least 6 months after diagnosis, and the presence of circulating pancreatic islet autoantibodies. The prevalence of LADA varies substantially across ethnic groups and ranges approximately from 1% to 10% among patients with type 2 diabetes. In this review we discuss the nomenclature, diagnostic criteria, immunologic and genetic markers, metabolic alterations and therapy of this form of diabetes.

Helicobacter pylori CagA antibodies and thyroid function in latent autoimmune diabetes in adults.

OBJECTIVE: H. pylori infection is reportedly associated with autoimmune diseases such as chronic thyroiditis and autoimmune diabetes. The aim of this study is to determine the association between H. pylori infection and its virulent strain CagA with antibodies against thyroperoxidase (TPO Ab) and thyrotropin (TSH) in a cohort of latent autoimmune diabetes in adult (LADA) patients. PATIENTS AND METHODS: We included 234 LADA patients (53.8% women). Antibodies against H. pylori whole antigens and CagA, TPO Ab and TSH were assessed in all patients. RESULTS: Prevalence of IgG against H. pylori and GagA was 52.1% and 20.9% respectively. Antibodies against H. pylori were not associated with TPO Ab and TSH (rho = 0.067, p = 0.620 and rho = 0.156, p = 0.099, respectively). Antibodies against CagA showed a positive association with TSH and TPO Ab (respectively rho = 0.309, p = 0.036 and rho = 0.419, p = 0.037). Subjects with hypothyroidism (TSH ≥ 3.5 µU/ml) had an increased frequency of Ab anti CagA (p = 0.059). CONCLUSIONS: The infection by H. pylori strains expressing CagA is associated with increased TPO Ab and TSH levels in LADA patients, suggesting a possible mechanism involved in thyroid autoimmunity and dysfunction of the gland. Further research is needed to test this hypothesis.

Male longevity in Sardinia, a review of historical sources supporting a causal link with dietary factors.

The identification of a hot spot of exceptional longevity, the Longevity Blue Zone (LBZ), in the mountain population of Sardinia has aroused considerable interest toward its traditional food as one of the potential causal factors. This preliminary study on the traditional Sardinian diet has been supported by the literature available, which has been carefully reviewed and compared. Up to a short time ago, the LBZ population depended mostly upon livestock rearing, and consumption of animal-derived foods was relatively higher than in the rest of the island. The nutrition transition (NT) in urbanized and lowland areas began in the mid-1950s, fueled by economic development, whereas in the LBZ it started later owing to prolonged resistance to change by a society organized around a rather efficient pastoral economy. Even nowadays a large proportion of the population in this area still follows the traditional diet based on cereal-derived foods and dairy products. The LBZ cohorts comprising individuals who were of a mature age when NT began may have benefited both from the high-quality, albeit rather monotonous, traditional diet to which they had been exposed most of their life and from the transitional diet, which introduced positive changes such as more variety, increased consumption of fruits and vegetables and moderate meat intake. It could be speculated that these changes may have brought substantial health benefits to this particular aging group, which was in need of nutrient-rich food at this specific time in life, thereby resulting in a decreased mortality risk and, in turn, life-span extension.

Paired neurophysiological and clinical study of the brainstem at different stages of Parkinson's Disease.

OBJECTIVE: To study brainstem function in Parkinson's Disease (PD) at different stages, through a battery of vestibular-evoked myogenic potentials (VEMPs) and compare the results with scores on clinical scales assessing the presence of symptoms linked to brainstem involvement. METHODS: Cervical, masseter and ocular VEMPs were recorded in patients with early PD (n=14, disease duration 1.42±0.7years), advanced PD (n=19, disease duration 7.26±2.9years) and in 27 age-matched controls. In PD, the following clinical scales were administered: Mini-BESTest, REM sleep Behavior Disorder Screening Questionnaire (RBD-SQ), PD Sleep Scale, Epworth Sleepiness Scale and Geriatric Depression Scale. RESULTS: Rate of VEMPs alterations was higher (p<0.001) in PD than controls, but similar within PD groups. However, early and advanced PD showed a different pattern of abnormalities (p=0.02), being latency delay prevalent in the former and absence in the latter. VEMP impairment correlated directly with RBD-SQ scores in both PD cohorts and inversely with Mini-BESTest scores in advanced PD. CONCLUSIONS: VEMPs displayed progressive severity of alterations at different stages of PD, with remarkable correlations with presence of postural instability and RBD. SIGNIFICANCE: The combined use of VEMPs may provide interesting insights into the pathophysiological mechanisms of PD at the earliest and prodromal stage of the disease.

Reduced intravenous glutathione in the treatment of early Parkinson's disease.

1. Several studies have demonstrated a deficiency in reduced glutathione (GSH) in the nigra of patients with Parkinson's Disease (PD). In particular, the magnitude of reduction in GSH seems to parallel the severity of the disease. This finding may indicate a means by which the nigra cells could be therapeutically supported. 2. The authors studied the effects of GSH in nine patients with early, untreated PD. GSH was administered intravenous, 600 mg twice daily, for 30 days, in an open label fashion. Then, the drug was discontinued and a follow-up examination carried-out at 1-month interval for 2-4 months. Thereafter, the patients were treated with carbidopa-levodopa. 3. The clinical disability was assessed by using two different rating scale and the Webster Step-Second Test at baseline and at 1-month interval for 4-6 months. All patients improved significantly after GSH therapy, with a 42% decline in disability. Once GSH was stopped the therapeutic effect lasted for 2-4 months. 4. Our data indicate that in untreated PD patients GSH has symptomatic efficacy and possibly retards the progression of the disease.

Extremely high HDL levels in a patient with multiple symmetric lipomatosis.

An extreme form of hyperalphalipoproteinemia was studied in a patient affected by multiple symmetric lipomatosis (MSL); four relatives and three MSL controls were also evaluated. Plasma lipids and apolipoproteins were measured and overall lipoprotein profile was assessed by density gradient ultracentrifugation. The patient showed a plasma HDL-cholesterol of 138 mg/dl and an apo A-I of 218 mg/dl; moreover significantly high HDL levels were found in two unaffected relatives. The hypobetalipoproteinemia trait was also found both in the patient and in one of his daughters. We suggest that some pre-existing conditions may enhance lipoprotein metabolism alterations in this lipid storage disease.

Number of autoantibodies and HLA genotype, more than high titers of glutamic acid decarboxylase autoantibodies, predict insulin dependence in latent autoimmune diabetes of adults.

OBJECTIVE: In latent autoimmune diabetes of adults (LADA), the progression into insulin-dependent diabetes is usually faster than in type 2 diabetes (T2D) but the factors influencing this progression are not completely known. In this study, we searched for sensitive markers associated with early development of insulin dependence. DESIGN: The screening of 5568 T2D patients for glutamic acid decarboxylase autoantibodies (GAD65Ab) identified 276 LADA patients (M=131; F=145) and in 251 of them, tyrosine phosphatase-2 (IA-2Ab) and thyroperoxidase autoantibodies (TPOAbs), some clinical features and genotype variation of the main type 1 diabetes (T1D) disease susceptibility loci (HLA-DRB1 and HLA-DQB1) were analyzed. RESULTS: Four years after the diagnosis of diabetes, high GAD65Ab titer was not significantly associated with faster progression toward insulin deficiency (P=0.104). Patients with GAD65Ab and TPOAb or IA-2Ab or triple positivity for both islet and TPOAbs (GAD65Ab/IA-2Ab/TPOAb) showed a significantly faster disease progression (P=0.002). Among 104 TPOAb-positive LADA patients, 10 received replacement therapy (l-thyroxine), 43 showed high TSH levels (62.7% developed insulin dependence), and 3 had hyperthyroidism treated with methimazole. Multivariate analysis revealed a significant effect on disease progression only for TPOAb (P=0.022), female gender (P=0.036), low body mass index (BMI; P=0.001), and T1D high/intermediate risk HLA-DRB1/DQB1 genotypes grouped (P=0.020). CONCLUSIONS: High GAD65Ab titers per se are not a major risk factor for disease progression in LADA, while the number of positive autoantibodies and HLA DRB1-DQB1 genotypes at high risk for T1D are significant predictors. Moreover, clinical characteristics such as low BMI and female gender are more likely to identify patients who will require insulin therapy within 4 years of diagnosis.

[Severe hypertriglyceridemia without organ complications in an alcoholic non-diabetic patient]. / Grave ipertrigliceridemia senza complicanza d'organo in un paziente alcolista non diabetico.

A case report of a non-diabetic alcoholic patient (ethanol intake >220 g/d) who experienced severe hypertriglyceridemia (12.679 mg/dL) without pancreatitis or detectable genetic factors responsible for severe dyslipidemia is described. Following the normalization of triglyceride and cholesterol levels, through lipid-free parenteral nutrition therapy, a regimen of alcohol withdrawal and a well-balanced diet with less than 10% saturated fat maintained a normal lipid profile without requiring any lipid-lowering drug. The absence of organ damage in the patient is likely to be attributed to the short duration of the elevated triglyceride peak. The treatment of this disorder does not necessarily require LDL-apheresis but can be simply managed by parenteral therapy provided that no other risk factors are present.

Inflammatory biomarkers in blood of patients with acute brain ischemia.

Although many failed surrogate markers are provided in the literature, inflammation may contribute to the outcome of ischemic stroke. In 50 consecutive patients with acute ischemic stroke, in the absence of symptoms and signs of concomitant infection, we evaluated a panel of biomarkers reported to be variably associated with brain ischemia, and correlate their serum level with the brain lesion volume and clinical outcome. Infarct size was calculated on computed tomography (CT) scans by means of the Cavalieri's method. Neurological impairment was scored by using the Glasgow Coma Scale, Glasgow Outcome Scale and National Institutes of Health (NIH) scales at stroke onset and 3-month follow-up. Some markers showed a direct significant correlation with both initial and final NIH scale and with infarct size, particularly tumor necrosis factor alpha (TNF-alpha) (P=0.002), intercellular adhesion molecule-1 (P<0.01) and matrix metalloproteinase-2/9 (P=0.001). In contrast to previous reports, interleukin-6 (IL-6) serum level showed a significant inverse correlation with both final neurological impairment and infarct size (P<0.001). This novel finding allows us suggesting that IL-6, in the context of a complex pro-inflammatory network occurring during stroke, is associated with neuroprotection rather than neurotoxicity in patients with ischemic brain injury.

[Embryotoxicity of fenbendazole in Paracentrotus lividus]. / Embriotossicità del fenbendazolo in Paracentrotus lividus.

The aim of the present work was to evaluate the embryotoxicity of Fenbendazole, a benzimidazole carbamate-derived anthelmintic drug widely employed in Veterinary Medicine, by using the embryonal development of Paracentrotus lividus (sea urchin) as a experimental model. Embryos were obtained by in vitro eggs fertilization and cultured in seawater. Five embryo suspensions were added by Fenbendazole reaching a final concentration of 5 micrograms/l, 7.5 micrograms/l, 10 micrograms/l, 12.5 micrograms/l and 25 micrograms/l; a suspension was kept drug-free as a control. Embryo development was evaluated by microscopical examination of suspensions at 3 and 40 hours. Our results show that a concentration of 5 micrograms/l of the drug determines a considerable delay of the embryonal development in the 95 percent of the elements observed, and a concentration of 25 micrograms/l produces a block of the embryogenesis at the phase of morula and blastula in all embryos. Results confirm that the effects observed are probably due to an extended inhibition of several enzyme complexes of the embryo cells.

[Lipid and lipoprotein profile in psoriasis]. / Assetto lipidico e lipoproteico nella psoriasi.

Psoriasis is a common relapsing dermatosis characterized by an increased epidermal cell proliferation. In this work we studied the lipid and lipoprotein pattern in 17 patients affected by long-standing psoriasis and in 20 normal controls. Total cholesterol, triglyceride, HDL-cholesterol and Apolipoprotein AI and B levels were measured; VLDL, LDL and HDL chemical composition was assessed by preparative ultracentrifugation. Plasma lipid and lipoprotein levels were significantly lower in the patient group; chemical analysis of the main lipoprotein classes showed compositional abnormalities consistent with an accelerated turnover of these particles. We believe that epidermal cell proliferation can play a role in determining these changes.

Metabolic and renal effects of Laevo-carnitine and propionyl-carnitine in rats with subtotal nephrectomy.

The renal and metabolic effects of chronic carnitine administration were evaluated in the early stages of experimentally-induced renal failure. Laevo-carnitine (n = 5), Propionyl-carnitine (n = 5) both at 200 mg kg-1 of body weight, or vehicle (physiological saline solution, 0.4 ml kg-1 body weight, n = 5) were administered daily for 3 days prior to 2/3 nephrectomy and for 25 days thereafter, by intraperitoneal route. At the end of the experiment, no significant differences were found in systolic blood pressure and heart rate among groups. During the 25 days after nephrectomy, body weight increased by 71 +/- 13 g in the control group and by 50 +/- 26 g and 42 +/- 9 g in Laevo-carnitine and Propionyl-carnitine groups, respectively (P < 0.05 vs control for both comparisons). Urinary sodium excretion was increased in carnitine-treated rats (Laevo-carnitine: from 1.03 +/- 0.3 to 1.36 +/- 0.3 mEq day-1, Propionyl-carnitine: from 1.2 +/- 0.2 to 1.66 +/- 0.2 mEq day-1, P < 0.05 for both comparisons), but not in those given vehicle. Twenty-five days after nephrectomy, plasma creatinine was lower in carnitine-treated rats (Laevo-carnitine: 0.98 +/- 0.12 mg dl-1, Propionyl-carnitine: 1.06 +/- 0.15, vehicle: 1.52 +/- 0.09, P < 0.05 vs control for both comparisons). Plasma triglycerides and VLDL were decreased by nephrectomy and this effect was prevented by carnitine treatment. The data indicate that the carnitine blunts the increase in plasma creatinine that occurs early after partial nephrectomy and normalizes the plasma lipoprotein pattern. Thus, carnitine might protect against the development of renal failure in this experimental model.

Lack of influence of apolipoprotein E4 on lipoprotein levels in the island population of Sardinia.

BACKGROUND: In this study, the apolipoprotein E (apoE) genotypes as well as plasma lipid and lipoprotein levels have been determined for the first time in 633 healthy and unrelated inhabitants on the island of Sardinia (291 men and 342 women, age range 6-89 years), randomly selected in the four districts of Sardinia among healthy people having parents and grandparents born in the same geographic area. This island lies in the centre of the western Mediterranean sea with a well-recognized peculiar and preserved genetic background. The epsilon 3 allele frequency (0.897) is higher than that previously reported in southern and mainland Italy and is one of the highest in Europe and among Caucasians; epsilon 2 allele frequency (0.040) is the lowest in Europe; epsilon 4 (0.063) is unusually low and, most interestingly, does not change in the different age groups, i.e. does not decrease in old subjects. RESULTS: Lipid and lipoprotein analysis confirm that total cholesterol and low-density lipoprotein (LDL)-cholesterol levels are lower than those described in mainland Italy; moreover, in this large Sardinian series, accurately selected, epsilon 4 allele did not influence total cholesterol (P = 0.270), LDL-cholesterol (P = 0.667) and high-density lipoprotein (HDL)-cholesterol (P = 0.549) as in other populations. In contrast, subjects carrying the epsilon 2 allele were found to have significantly lower total cholesterol (P = 0.001) and LDL-cholesterol (P = 0.001) levels than epsilon 3 carriers. CONCLUSION: The low epsilon 4 frequency and the lack of influence of this allele on lipid metabolism is a unique characteristic and, to date, has been described only in Sardinia among Caucasians; it might contribute to the low prevalence of coronary artery disease in this island.