PARP-1 activation causes neuronal death in the hippocampal CA1 region by increasing the expression of Ca(2+)-permeable AMPA receptors.

An excessive activation of poly(ADP-ribose) polymerases (PARPs) may trigger a form of neuronal death similar to that occurring in neurodegenerative disorders. To investigate this process, we exposed organotypic hippocampal slices to N-methyl-N'-nitro-N'-nitrosoguanidine (MNNG, 100µM for 5min), an alkylating agent widely used to activate PARP-1. MNNG induced a pattern of degeneration of the CA1 pyramidal cells morphologically similar to that observed after a brief period of oxygen and glucose deprivation (OGD). MNNG exposure was also associated with a dramatic increase in PARP-activity and a robust decrease in NAD(+) and ATP content. These effects were prevented by PARP-1 but not PARP-2 inhibitors. In our experimental conditions, cell death was not mediated by AIF translocation (parthanatos) or caspase-dependent apoptotic processes. Furthermore, we found that PARP activation was followed by a significant deterioration of neuronal membrane properties. Using electrophysiological recordings we firstly investigated the suggested ability of ADP-ribose to open TRPM2 channels in MNNG-induced cells death, but the results we obtained showed that TRPM2 channels are not involved. We then studied the involvement of glutamate receptor-ion channel complex and we found that NBQX, a selective AMPA receptor antagonist, was able to effectively prevent CA1 neuronal loss while MK801, a NMDA antagonist, was not active. Moreover, we observed that MNNG treatment increased the ratio of GluA1/GluA2 AMPAR subunit expression, which was associated with an inward rectification of the IV relationship of AMPA sEPSCs in the CA1 but not in the CA3 subfield. Accordingly, 1-naphthyl acetyl spermine (NASPM), a selective blocker of Ca(2+)-permeable GluA2-lacking AMPA receptors, reduced MNNG-induced CA1 pyramidal cell death. In conclusion, our results show that activation of the nuclear enzyme PARP-1 may change the expression of membrane proteins and Ca(2+) permeability of AMPA channels, thus affecting the function and survival of CA1 pyramidal cells.

Could androgen receptor gene CAG tract polymorphism affect spermatogenesis in men with idiopathic infertility?

PURPOSE: This study examined whether the AR-CAG repeat length might affect clinical characteristics (testis volume) seminal parameters (sperm count and its mobility) along with hormonal serum profile [FSH, LH, Testosterone (T) and Inhibin B (InhB)] both in idiopathic male infertility (IM) and in infertility due to a previous condition of cryptorchidism (CryM) or to Y chromosome long arm microdeletions (YM). DESIGN: Observational study without intervention(s). PATIENTS: One hundred and ten IM patients [90 idiopathic olizoospermic males (IOM) and 20 idiopathic azoospermic males (IAM)], 19 CryM male and 10 YM patients were included. Sixty-one age-matched healthy men who had fathered within 3 years were involved representing the control group (FM). RESULTS: AR-CAG repeats stretch was significantly longer in IOM (p<0.05), CryM (p<0.05) and YM (p<0.001) than FM. When the AR-CAG repeat tracts were subdivided in three subgroups according to the length of CAG repeats tract assessed in fertile subjects (the one with the middle (n 19-21) belonging to the 25 and 75 % inter-quartile, the ends belonging to the <25 % inter-quartile and >75 % inter-quartile, respectively), there was a statistically significant difference of distribution of AR-CAG tract length among fertile and different groups of infertile men (p=<0.0005; chi-square test). Moreover, the subgroup of AR-CAG repeat stretch with 22-28 triplets was associated with lower levels of InhB both in idiopathic oligozoospermic (Scheffe, Bonferroni and Dunett tests p=<0.01) and azoospermic men (Scheffe, Bonferroni and Dunett test p=<0.05), while, when FM and men with idiopathic infertility were gathered in a single group, both the subgroup of AR- CAG tract with 15-18 repeats and the one with 22-28 repeats are associated with lower testis volume, reduced sperm count and serum InhB levels. CONCLUSIONS: Our study showed that the outliers of AR-CAG repeat length seem to influence the function of AR, affecting testis volume and Sertoli cell function and consequently sperm production in both fertile and idiopathic infertile men.

Diet and myocardial infarction: a nested case-control study in a cohort of elderly subjects in a Mediterranean area of southern Italy.

BACKGROUND AND AIM: We evaluated the incidence of myocardial infarction (MI) in a population of Southern Italy and the relationship of dietary macronutrients with incident MI. METHODS AND RESULTS: The ONCONUT cohort included 5632 subjects followed-up, over 50 years, recruited in 1992. At baseline, they completed a validated semi-quantitative food frequency questionnaire and gave details of their medical history. After 5years they were traced by their family physician, who found 108 incident MI. Ninety-seven of them and 194 controls, sampled from the noncases at baseline and paired for diabetes to the cases, entered this nested case-control study. MI rate per 1000 person-years was 9.6 in males and 3.7 in females. In non-diabetics, saturated fat were associated with MI directly (odds ratio (OR): tertile 2 vs. 1 = 2.32, tertile 3 vs. 1 = 2.82; chi-square for trend, p = 0.03) and polyunsaturated fats inversely (OR: tertile 2 vs. 1 = 0.80, tertile 3 vs. 1 = 0.37; chi-square for trend, p = 0.05), while in diabetics, starchy carbohydrates (OR: tertile 2 vs. 1 = 1.51, tertile 3 vs. 1 = 6.73; chi-square for trend, p = 0.01) and glycaemic index (OR: tertile 2 vs. 1 = 2.74, tertile 3 vs. 1 = 5.34; chi-square for trend, p = 0.01) were associated directly with MI. CONCLUSIONS: MI incidence in this population was lower than that found in northern countries. In non-diabetics, saturated fats were associated directly and polyunsaturated fat inversely with MI; in diabetics, starchy carbohydrates and high-glycaemic-index foods were associated directly with MI.

Vasopressin release induced by hypothension is blunted in patients with diabetic autonomic neuropathy.

The response of arginin-vasopressin (AVP) to baroreceptor activation (tilt testing) was investigated in patients with diabetic autonomic neuropathy (DAN). The present data show that hypothension induced by upright position showed a slight increase of AVP in patients with DAN in comparison with normal subjects and diabetic patients without DAN. These findings suggest that the blunted AVP response to hypothension may be due to lesions of afferent autonomic pathways present in DAN and plays a role in the pathogenesis of postural hypothension.

Difference in growth hormone response to growth hormone-releasing hormone (GHRH) testing following GHRH subacute treatment in normal aging and growth hormone-deficient adults: possible perspectives for therapeutic use of GHRH or its analogs in elderly subjects?

The somatotroph axis function shows a decline in the elderly (somatopause). In particular growth hormone (GH) response to GH-releasing hormone (GHRH) is reduced in aged man but less than that observed in GH-deficient adults (GHDAs). Plasma GH response to GHRH (1 µg/kg BW) was significantly lower in four GHDAs than in seven healthy aged men 30, 60, and 90 min after acute GHRH administration. To verify whether a priming regimen might be able to increase the reduced GH response to GHRH, both healthy aged men and GHDA patients underwent repetitive administration of GHRH (100 µg GHRH intravenously as a single morning dose, every 2 days for 12 days). After the GHRH-priming regimen, plasma GH values 30, 60, and 90 min after the acute GHRH test were significantly higher than values at the corresponding time points before priming regimen in healthy aged men but not in GHDA patients. These findings confirmed that somatotroph cells become less sensitive to GHRH with normal aging and demonstrate that repetitive administration of GHRH restores the attenuated response only in healthy aged men but not in GHDA patients. This could support the possible use of GHRH or its analogs instead of recombinant human GH in elderly patients with the advantage of preserving the endogenous pulses of GH with the secretion of the different isoforms of GH. However, concerns arise about the possible role of these molecules in tumorigenesis and tumor growth promotion.

Selective HCN1 block as a strategy to control oxaliplatin-induced neuropathy.

Chemotherapy-Induced Peripheral Neuropathy (CIPN) is the most frequent adverse effect of pharmacological cancer treatments. The occurrence of neuropathy prevents the administration of fully-effective drug regimen, affects negatively the quality of life of patients, and may lead to therapy discontinuation. CIPN is currently treated with anticonvulsants, antidepressants, opioids and non-opioid analgesics, all of which are flawed by insufficient anti-hyperalgesic efficacy or addictive potential. Understandably, developing new drugs targeting CIPN-specific pathogenic mechanisms would dramatically improve efficacy and tolerability of anti-neuropathic therapies. Neuropathies are associated to aberrant excitability of DRG neurons due to the alteration in the expression or function of a variety of ion channels. In this regard, Hyperpolarization-activated Cyclic Nucleotide-gated (HCN) channels are overexpressed in inflammatory and neuropathic pain states, and HCN blockers have been shown to reduce neuronal excitability and to ameliorate painful states in animal models. However, HCN channels are critical in cardiac action potential, and HCN blockers used so far in pre-clinical models do not discriminate between cardiac and non-cardiac HCN isoforms. In this work, we show an HCN current gain of function in DRG neurons from oxaliplatin-treated rats. Biochemically, we observed a downregulation of HCN2 expression and an upregulation of the HCN regulatory beta-subunit MirP1. Finally, we report the efficacy of the selective HCN1 inhibitor MEL57A in reducing hyperalgesia and allodynia in oxaliplatin-treated rats without cardiac effects. In conclusion, this study strengthens the evidence for a disease-specific role of HCN1 in CIPN, and proposes HCN1-selective inhibitors as new-generation pain medications with the desired efficacy and safety profile.

A Herpes simplex virus-1 fatal encephalitis following chemo-radiotherapy, steroids and prophylactic cranial irradiation in a small cell lung cancer patient.

Approximately 20-25% of patients with limited small cell lung cancer (SCLC) can be cured with an aggressive approach (chest radiation concomitant with chemotherapy) followed by prophylactic cranial irradiation (PCI) to a total dose of 30-36Gy with 3-2Gy per fraction, five fractions per week. Steroid prophylactic therapy with dexamethasone is usually prescribed during PCI to minimize acute radiation induced brain oedema. This approach may induce an immunosuppressive condition leading to a reactivation of an endogenous latent Herpes simplex virus and severe or fatal acute encephalitis may occur as our report will show. A 55-year-old man affected by locally advanced SCLC was referred to our institution after four cycles of chemotherapy with a good partial remission. Chest radiation started concomitantly with two cycles of chemotherapy followed by PCI 36Gy total dose and dexamethasone 8mg i.m. daily. Fifteen days after PCI completion the patient developed acute neurological symptoms of confusion, cognitive impairment, fever with shaking requiring severe sedation therapy. Twenty-five days later MRI T1 weighted images showed haemorrhagic streaked lines on cortical convolutions of the right cerebral hemisphere and diffuse oedema suggestive of herpetic encephalitis. The DNA consensus test on cerebrospinal fluid (CSF) was positive for Herpes simplex virus 1 infection (HSV-1). A diagnosis of herpetic encephalitis HSV-1 was made. Antiviral therapy with high doses of acyclovir was prescribed but symptoms did not ameliorate leading to a comatose state. The patient died 55 days after the end of PCI. In eligible SCLC patients, PCI is an important part of an aggressive therapeutic approach that improves overall and disease free survival decreasing the risk of relapse in the brain. A primary infection or a reactivation of an endogenous latent HSV in brain parenchyma under steroid therapy concomitant to brain irradiation may compromise these benefits.

Evolution of a prolactin-secreting pituitary microadenoma into a fatal carcinoma: a case report.

Pituitary carcinomas are very rare tumors, nearly always presenting as widely invasive masses, although the hallmark of these lesions is the finding of distant metastases. One third of reported cases are prolactin (PRL)-secreting tumors. We report the case of a fatal pituitary carcinoma evolving within 4 years from a PRL-secreting microadenoma. A 22-year-old woman presented because of galactorrhea. Evaluation of the patient disclosed slight hyperprolactinemia and magnetic resonance imaging (MRI) showed a 7-mm intrapituitary lesion, which responded to treatment with cabergoline. About 4 years after the first evaluation she developed sudden headache, ptosis, and diplopia in the right eye. MRI disclosed the growth of a large pituitary mass, invading the right cavernous sinus. Despite two trans-sphenoidal surgical procedures followed by gamma-knife radiosurgery, the patient showed rapid local progression of the tumor and the occurrence of new lung lesions, probably of metastatic nature. The patient died 7 months after the development of her first neurological symptoms because of tumor apoplexy and subsequent subarachnoid hemorrhage. This case represents the first documented rapid evolution from a microprolactinoma initially responding to dopamine agonists to a fatal pituitary carcinoma.

Optical mapping of neuronal activity during seizures in zebrafish.

Mapping neuronal activity during the onset and propagation of epileptic seizures can provide a better understanding of the mechanisms underlying this pathology and improve our approaches to the development of new drugs. Recently, zebrafish has become an important model for studying epilepsy both in basic research and in drug discovery. Here, we employed a transgenic line with pan-neuronal expression of the genetically-encoded calcium indicator GCaMP6s to measure neuronal activity in zebrafish larvae during seizures induced by pentylenetretrazole (PTZ). With this approach, we mapped neuronal activity in different areas of the larval brain, demonstrating the high sensitivity of this method to different levels of alteration, as induced by increasing PTZ concentrations, and the rescuing effect of an anti-epileptic drug. We also present simultaneous measurements of brain and locomotor activity, as well as a high-throughput assay, demonstrating that GCaMP measurements can complement behavioural assays for the detection of subclinical epileptic seizures, thus enabling future investigations on human hypomorphic mutations and more effective drug screening methods. Notably, the methodology described here can be easily applied to the study of many human neuropathologies modelled in zebrafish, allowing a simple and yet detailed investigation of brain activity alterations associated with the pathological phenotype.

Thromboaspiration technique as first approach for endovascular treatment of acute ischemic stroke: initial experience at nine Italian stroke centers.

BACKGROUND AND PURPOSE: Aspiration thrombectomy of large vessel occlusions has made a comeback among recanalization techniques thanks to recent advances in catheter technology resulting in faster recanalization and promising clinical results when used either alone or as an adjunct to stent retriever. This multicenter retrospective study reports angiographic data, complications, and clinical outcome in patients treated with aspiration thrombectomy as the first-line option. MATERIALS AND METHODS: We analysed the clinical and procedural data of patients treated from January 2014 to March 2015. Recanalization was assessed according to the Thrombolysis in Cerebral Infarction score. Clinical outcome was evaluated at discharge and after 3 months. RESULTS: Overall, 152 patients (mean age 68 years) were treated. Sites of occlusion were 90.8% anterior circulation (including 16.4% tandem extracranial/intracranial occlusions) and 9.2% basilar artery. In 79 patients administration of intravenous tissue plasminogen activator was attempted. Recanalization of the target vessel was obtained in 115/152 cases (75.6%) whereas direct aspiration alone was successful in 83/152 cases (54.6%) with an average puncture to revascularization time of 44.67 min. Symptomatic intracranial hemorrhage occurred in 7.8% and embolization to new territories in 1.9%. 77 patients (50.6%) had a good outcome at 90-day follow-up: 55/96 in the direct aspiration alone group and 22/56 in the aspiration-stent retriever group. CONCLUSIONS: Direct aspiration thrombectomy appears a feasible technique with good revascularization results achieved in more than half the patients. In light of the self-reported data, inhomogeneous patient selection, absence of a core imaging laboratory, and a non-standardized approach, the results should be validated in a larger trial.

Ablation of T-helper 1 cell derived cytokines and of monocyte-derived tumor necrosis factor-alpha in hereditary hemorrhagic telangiectasia: immunological consequences and clinical considerations.

Experimental evidences on the adaptive immune response in patients with hereditary hemorragic telagiectasia (HHT) are lacking. Here, we report in 9 patients with HHT a multiple deficit involving the intracellular expression of T helper (h)1-derived cytokines [Interferon (IFN)-gamma, Interleukin (IL)-2 and Tumor Necrosis Factor (TNF)-alpha] and of monocyte-derived TNF-alpha. On the other hand, percentages of Th2-derived cytokines (IL-4, IL-5 and IL-10) were normal or, in some cases, above normality. Quite interestingly, monocyte-derived IL-10 was detectable in 5 out of 9 patients in a percentage of cells comparable to controls or exceeding normal levels. Taken together, these data point out, in HHT, an ablation of Th1-responses, while Th2-type cytokines are preserved, thus exerting either a suppressive effect on Th1-cells (via IL-4 and IL-10) or an antiinflammatory response on monocyte-derived TNF-alpha (via IL-10). Furthermore, monocyte-derived IL-10 may also contribute to the antiinflammatory activity seen in HHT. According to current literature even if patients with HHT do not exhibit certain diseases, such as autoimmune diseases, cancer and abnormal responses to pathogens, the observed immune deficits need to be diagnosed and therapeutically corrected.

HHT: a rare disease with a broad spectrum of clinical aspects.

HHT is an autosomal dominant disease characterised by diffuse muco-cutaneous and visceral telangiectases in potentially all organs. Mutations in two different genes identify HHT type 1 and HHT type 2: endoglin located on chromosome 9q33-q34 and ALK-1 or ACVRL1 on chromosome 12q13, respectively. The existence of a third locus has also been hypothesised. HHT-1 is considered a more severe form of the disease with an earlier onset of epistaxis and telangiectases and a higher prevalence of pulmonary arteriovenous malformations than that found in HHT-2 subjects. Usually, a typical HHT patient has epistaxis, muco-cutaneous telangiectases and GI bleeding in later life, even though this clinical scenario represents only one of the possible HHT patterns. In fact, vascular malformations often remain silent until the onset of a severe complication, which frequently is the first clinical manifestation of HHT. The lung and brain are of particular concern because each may contain clinically silent lesions that can result in sudden morbidity and mortality. At present, awaiting the availability of genetic testing, only an expert in the clinical patterns and diagnostic imaging of HHT can permit a definite diagnosis in individuals at high risk for the disease.

Life expectancy in patients with hereditary haemorrhagic telangiectasia.

BACKGROUND: There are few data on life expectancy in patients with hereditary haemorrhagic telangiectasia (HHT), a disorder with life-threatening complications. METHODS: Seventy HHT patients provided data on age and age at death of their HHT-affected parent, which was compared with that of the parent's non-affected partner. RESULTS: At the time of the study, 40 HHT parents (57.1%) vs. 36 (51.4%) non-HHT parents had died (p = 0.404). Median age at death was lower in HHT vs. non-HHT parents (63.2 vs. 70.0 years, respectively). The mortality of HHT parents showed an early peak in the under 50s and a late peak at 60-79 years. HHT was the main risk factor influencing life expectancy after 30 years (p < 0.05). No differences in survival probability were found in HHT patients with respect to sex (p = 0.37), or ENG vs. ALK-1 genotype (p < 0.9). DISCUSSION: Life expectancy appears to be significantly lower in HHT patients than in their partners. Prevention of HHT complications with screening programs could increase life expectancy.

Increased CD34+ cell peripheral traffic appears to be an unique feature of the allergic inflammation.

Evidence has been cumulated during the last years concerning the immaturity of the cells involved in the local and systemic aspects of allergic inflammation. Hematopoietic precursors (HPC) are mobilized from the bone matrix as multipotent cells or, more often, as progenitors that, after the initial white-lineage commitment reach through the peripheral blood (PB) their final destinations constituted by the target organs of allergy. Although several studies have investigated the CD34+ cells traffic and location at the level of the inflamed peripheral mucosae in allergic populations, limited information is available on their behaviour on the time-course of infectious diseases. The current study thus was designed to asses the peripheral traffic of CD34+ HPC during the infectious inflammation. To this end CD34+ HPCs have been enumerated, by flow-cytometric techniques, in PB of 24 adult healthy beings (Group A), 24 adult subjects with symptomatic extrinsic allergy (Group B) and in PB of 24 adult patients hospitalised for febrile infectious pathology (Group C). CD34+ cell values ranged 0.01-0.08% with a median of 0.03 in Group A. In Group B values ranged 0.17-0.75% with a median of 0.28 and in Group C values ranged 0.00-0.12% with a median of 0.07. Variance analysis test among the three groups was statistically significant (p<0.001) supporting the conclusion that CD34+ HPC mobilizing and increased peripheral traffic is an unique feature of the allergic inflammation.

Nutrition and immunity: laboratory and clinical aspects.

It is well known that inappropriate nutrient intake accounts for the maintenance of the immunological equilibrium, in humans and animals. Vitamins, elements, lipids, proteins and nucleic acids play an important role in the regulation of cellular and humoral immune responses since single or multiple deficits of these food components have been shown to cause immune abnormalities. For instance, in the course of protein-calorie malnutrition bacterial and/or viral infections represent the major cause of death. Ageing is characterized by a decline of many immune functions, and this process is called immunosenescence. Here, we report novel findings on the inability of superantigens to activate old CD8+, natural killer and B cells, as an expression of cell amnesia. In the elderly, this lack of activation could lead to lethal effects in the case of severe staphylococcal infections. Quite interestingly, recent findings outlined some similarities between human immune deficiency virus (HIV)-1 infection and ageing in terms of immune changes. The model of HIV-infection may be useful for the interpretation of ageing mechanisms and possible therapeutical interventions. Finally, the role of nutrition in different pathological conditions and the use of medical foods for correcting of immune deficits will be described.

In search of a biological pattern for human longevity: impact of apo A-IV genetic polymorphisms on lipoproteins and the hyper-Lp(a) in centenarians.

We studied centenarians to investigate the biological basis of human longevity focusing on the apolipoprotein A-IV and lipoprotein(a), potentially involved in the susceptibility to atherogenic mechanisms. We analyzed two restriction polymorphisms, HinfI347 (alleles +, -) and Fnu4HI360 (alleles 1, 2), and a VNTR (alleles 3, 4) at the 3' region of the apo A-IV gene. The allele frequencies, the lipoprotein concentrations and their association in centenarians and adults have been compared. In centenarians, the HinfI genotype distribution is different (P < 0.05) and the (+13) haplotype is prevalent (0.54 vs. 0.39), with a greater association of (+3), indicating the selection of a favourable allele. The lipoprotein modulation by the apo A-IV polymorphisms is suggested by significant associations in adults ((+/+) homozygotes have lower LDL-cholesterol and apo B than heterozygotes; (1/1) homozygotes have higher TG and apo B than heterozygotes), that in centenarians still exists as a trend. Centenarians show peculiar lipoprotein features: lower LDL-cholesterol (mean 103 vs. 115 mg/dl; P < 0.02), and higher lipoprotein(a) (median 17.5 vs. 4.5; P < 0.002). Large part of them (47%), especially the Hinf(+/+) and the (+13) homozygotes, have a lipoprotein(a) > 20 mg/dl, value considered as the threshold for atherogenic risk, surprisingly compatible with healthy longevity.

Evidence for a putative relationship between type 2 diabetes and neoplasia with particular reference to breast cancer: role of hormones, growth factors and specific receptors.

The issue of a possible relationship between type 2 diabetes and cancer is still debated. Such chronic diseases show a high incidence in the general population. In their pathophysiology both genetic and environmental factors are involved, inducing important modifications of metabolism. Diabetes is associated to profound metabolic alterations, such as hyperinsulinemia and insulin resistance, which are common in various diseases, i.e. obesity, hypertension, dyslipidemia and hyperuricemia. Those illnesses form the so-called metabolic syndrome. Insulin resistance, hyperestrinism and the associated hyperandrogenism may play a role in the onset of some malignancies, such as endometrium cancer, breast cancer and prostate cancer. Low plasma levels of IGF-1 are able to reduce the risk of cancer in type 2 diabetes patients. This goal can be obtained with preventive measures, as physical activity, diet and drugs that can reduce insulin resistance (metformin and thiazolidinediones).

Breast cancer: biological characteristics in postmenopausal type 2 diabetic women. Identification of therapeutic targets.

HYPOTHESIS: Epidemiological data have suggested a possible relationship between diabetes mellitus and cancer risk, particularly breast cancer. We set out to investigate the effect of diabetes mellitus on the expression of estrogen and progesteron receptors and on the proliferative activity of primary breast cancer. METHODS: We selected 77 diabetic women and 578 control patients all in post-menopause and diagnosed with primary breast cancer. All patients underwent surgical excision of the tumor and on the specimens were performed an assessment of estrogen receptor and progesteron receptor and proliferative activity assay by (3)H-Thymidine incorporation. RESULTS: Diabetic women showed a decreased proliferative activity, while having the same estrogen receptor and progesteron receptor status and mean cytoplasmic concentration of their receptors than control group. Insulin treated women had a lower proliferative activity than non-insulin treated ones. CONCLUSION: Hyperinsulinemia and hyperglicemia influence in negative way the proliferative activity of diabetic women, likely inducing the expression of transforming growth factor beta, despite the high serum levels of Insulin-like growth factor and estrogen.

The impact of body mass index and type 2 diabetes on breast cancer: current therapeutic measures of prevention.

Epidemiological data have suggested a possible relationship between obesity, diabetes mellitus and cancer risk, particularly breast cancer. We set out to investigate the effect of body mass index and diabetes mellitus on the presence of breast cancer in the Apulian population. We selected 1,663 women affected with primary breast cancer and 4,702 control patients. All patients with breast cancer underwent surgical excision of the tumor and their tumors were histologically confirmed. The prevalence of type 2 diabetes (8%) in the women affected by breast cancer was significantly higher than in the control group (5%) (p<0.05). The majority of the diabetic women affected by breast cancer had a BMI value >25, both in premenopause and in postmenopause. With respect to BMI, the non-diabetic patients with breast cancer in postmenopause showed the same pattern as the diabetic ones. Instead, among the women in premenopause a higher percentage (55%) of patients with a BMI <24.9 was found (p<0.01). In the Apulian population, the presence of both type 2 diabetes and elevated values of BMI (that is in a condition of hyperinsulinemia) were found to enhance the frequency of breast cancer.

Prurigo nodularis (Hyde's prurigo) disclosing celiac disease.

A case of prurigo nodularis (Hyde's prurigo) preceding by 15 years the diagnosis of celiac disease is presented. In particular, the association between the clinical course of prurigo nodularis and the compliance with gluten-free diet is reported and discussed.