DOPAL derived alpha-synuclein oligomers impair synaptic vesicles physiological function.

Parkinson's disease is a neurodegenerative disorder characterized by the death of dopaminergic neurons and by accumulation of alpha-synuclein (aS) aggregates in the surviving neurons. The dopamine catabolite 3,4-dihydroxyphenylacetaldehyde (DOPAL) is a highly reactive and toxic molecule that leads to aS oligomerization by covalent modifications to lysine residues. Here we show that DOPAL-induced aS oligomer formation in neurons is associated with damage of synaptic vesicles, and with alterations in the synaptic vesicles pools. To investigate the molecular mechanism that leads to synaptic impairment, we first aimed to characterize the biochemical and biophysical properties of the aS-DOPAL oligomers; heterogeneous ensembles of macromolecules able to permeabilise cholesterol-containing lipid membranes. aS-DOPAL oligomers can induce dopamine leak in an in vitro model of synaptic vesicles and in cellular models. The dopamine released, after conversion to DOPAL in the cytoplasm, could trigger a noxious cycle that further fuels the formation of aS-DOPAL oligomers, inducing neurodegeneration.

In-label and off-label use of respiratory drugs in the Italian paediatric population.

AIM: To evaluate the prescription rate of respiratory drugs (ATC code R03) in an Italian community setting and to estimate the extent of off-label use by both age and indication. METHODS: A cohort study aimed at evaluating prescriptions of drugs with ATC code R03 was conducted for the period 2002-2006. Data source was the PEDIANET Database. RESULTS: Ninety percent of R03 prescriptions are covered by 11 active substances or combinations, corresponding to 67 medicinal products. Inhaled corticosteroids are the most prescribed anti-asthmatic agents, followed by short-acting beta2 mimetics. The mean off-label rate is 19 and 56%, by age and indication respectively. The majority of off-label uses is among children under the age of 2. Five active substances are used at dosages not supported by adequate dose-finding studies. CONCLUSION: In Italy, many respiratory drugs are approved for the treatment of paediatric respiratory diseases, but a remarkable percentage of their prescriptions is off-label. This pharmaco-utilization study demonstrates that there is a need to perform clinical studies aimed at increasing the current knowledge on marketed paediatric drugs, and to revise and re-label the existing regulatory documents to reduce their off-label uses.

Sensitivity and specificity of ultrasound indices of ovulation in spontaneous cycles.

OBJECTIVE: Evaluation of sensitivity and specificity of 4 ultrasound indices of ovulation. STUDY DESIGN: Multicenter collaborative study of 794 abdominal and transvaginal ultrasound scanning of ovaries performed during 271 cycles in 107 normally fertile women. Comparison of sensitivities and specificities of indices using McNemar test. RESULTS: The sensitivity and specificity of the indices were 84 and 89.2, respectively, for disappearance or sudden decrease in follicle size; 38.4 and 79.7 for appearance of ultrasonic echoes in the follicle; 61.6 and 87.1 for irregularity of follicular walls; 71.0 and 88.2 for appearance of free fluid in the cul-de-sac of Douglas. CONCLUSION: Ultrasonic echoes had a significantly lower sensitivity (P<0.001) and specificity (P<0.01) than other indices.

Comparing a public and private sector NFP program: implications for NFP expansion.

This paper synthesizes a six year collaboration between a natural family planning (NFP) non-governmental organization (NGO) and the National Health Service of the Emilia Romagna region in Italy. It also compares the public program experience with NFP services provided in the private sector in the adjacent region of Veneto. Midwives provided NFP services in government family health clinics while in the private sector NFP was taught by non-health laypersons in a church-based facility. The populations served by these two programs were different. Women in the public sector were slightly older and two-thirds were married. Forty percent of the clients had chosen to use NFP to achieve a pregnancy. The private sector client, recruited in part through premarriage counseling programs, was equally divided between married and single women, though the majority came for advice on avoiding or spacing pregnancies. In both regions NFP users were more highly educated than the general population.

The behavior of Italian family physicians regarding the health problems of women and, in particular, family planning (both contraception and NFP).

The hospital-centered trend that has dominated medical culture and the management of health care during this entire century has, in the last few years, undergone a reversal in Italy. Conditions in other countries suggest that similar changes have or will become increasingly common. The family physician today manages many of the functions previously handled by hospitals and specialists. In the field of reproductive health, family physicians are responsible not only for diagnosis and treatment, but also for prevention and education. The present study considers this new context with the objective of investigating the knowledge and behavior of Italian family physicians in the field of women's health, with particular regard to family planning (including natural family planning), through (1) a qualitative study (focus groups) of a small group of family physicians and (2) a questionnaire sent to 500 family physicians throughout Italy. The results of the focus group are summarized in the form of obstacles that the family physician finds in providing family planning services and proposals for change. The results indicate that because of their holistic approach, the family physician is an appropriate provider of family planning services although continued use of specialists' services, changes in logistics of the family physicians' practice, increased gender sensitivity, and additional training and information are necessary. The results of the questionnaire (121 responses, 24.2%) indicate that the Italian family physician currently lacks certain important information about family planning and would require logistical support to provide these services but is interested in acquiring information and is an appropriate family planning provider. An additional challenge for encouraging family practitioners to provide natural methods is that they favor a "medical" approach rather than a "behavioral" one in their treatment preferences for several other conditions.

The Verona diabetes study: a population-based survey on known diabetes mellitus prevalence and 5-year all-cause mortality.

This population-based survey aimed to determine the prevalence of known diabetes mellitus on 31 December 1986, and to assess all-cause mortality in the subsequent 5 years (1987-1991) in Verona, Italy. In the study of prevalence, 5996 patients were identified by three independent sources: family physicians, diabetes clinics, and drug prescriptions for diabetes. Mortality was assessed by matching all death certificates of Verona in 1987-1991 with the diabetic cohort. Overall diabetes prevalence was 2.61% (95% confidence interval 2.56-2.67). Prevalence of insulin-dependent and non-insulin-dependent diabetes mellitus was 0.069% (0.059-0.078) and 2.49% (2.43-2.54), respectively. Diabetes prevalence sharply increased after age 35 years up to age 75-79, and finally declined. Prevalence was higher in men up to age 69 years, in women after age 75 years. Of the diabetic cohort 1260 patients (592 men, 668 women) died by 31 December 1991, yielding an overall standardized mortality ratio of 1.46 (CI 1.38-1.54). Even though the differences narrowed with age, mortality rates in the diabetic cohort were higher than in the non-diabetic population at all ages. Women aged 65-74 years showed observed/expected ratio higher than men (2.27, CI 1.92-2.66, vs 1.50, CI 1.30-1.72), while in other age groups the sex-related differences were not significant. Pharmacological treatment of diabetes was associated with an excess mortality, while treatment with diet alone showed an apparent protective effect on mortality (observed/expected ratio 0.73, CI 0.58-0.92).(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of aging on growth hormone, ACTH and cortisol response to insulin-induced hypoglycemia in type I diabetes.

The influence of age on plasma growth hormone (GH) response to i.v. insulin (0.2 U/kg body weight) was evaluated in clinically stable type I (insulin-dependent) diabetics divided into four age groups (range 18.80 years). ACTH and cortisol were also assayed in two groups of diabetics under and over 50 years of age. A significant reduction with aging in GH response to insulin was observed. On the contrary, the glucose fall was similar in all the groups. ACTH and cortisol responses to insulin were slightly decreased in the older diabetics. Since insulin-induced hypoglycemia was similar in all the age groups, the progressive decline with aging in the GH response to insulin may be attributed to age-related changes of the pituitary gland. The data on ACTH and cortisol are less striking. Our data, as a whole, confirm that growth hormone response to insulin-induced glucose fall is not critical in acute glucose counterregulation in insulin-dependent diabetics. In fact, in spite of a 4-fold difference in GH levels, there was no difference in the 2-h glycemic course after 0.2 U/kg of i.v. insulin between young and aged patients. When a group of 26 type I diabetics with proliferative retinopathy was compared with a group of age-matched type I diabetics without retinopathy and with 30 age-matched normal subjects (injected i.v. with 0.1 U/kg body weight of insulin), no difference was found in GH response to insulin, indicating that GH hypersecretion is not a characteristic finding of diabetic retinopathy.