HPyV6, HPyV7 and TSPyV DNA sequences detection in skin disease patients and healthy subjects.

BACKGROUND: The discovery, from 2007, of eight new human polyomaviruses (HPyVs) has revived interest in the Polyomaviridae family and their association with human diseases and cancer. In particular, HPyV6 and HPyV7 were discovered in skin swabs of healthy donors and TSPyV was discovered in a heart transplant recipient affected by virus-associated Trichodysplasia Spinulosa (TS), a rare skin disease, exclusively found in immunocompromised patients. OBJECTIVE: The presence of HPyV6, HPyV7 and TSPyV DNA in skin biopsies from patients affected by different skin diseases (cancers and inflammatory disorders) has been evaluated to confirm their skin tropism and the possible pathological association. METHODS: DNA extracted was amplified with HPyV6, HPyV7 and TSPyV specific PCR real time on Taqman platform with standard profile. RESULTS: HPyV7 and TSPyV sequences were not found in any skin specimen analysed. HPyV6, on the other hand, was detected in 30% of samples from healthy subjects vs. 14.3% of skin cancer patients and 2.9% of inflammatory disorders. HPyV6 sequences have been detected in primary cutaneous T-cell lymphoma (CTCL) patients (in 18.6% out of Mycosis Fungoides (MF) patients and in 16.7% out of CTCL not MF/SS(Sèzary syndrome) but have not been detected in primary cutaneous B-cell lymphoma (CBCL) patients. CONCLUSION: Our preliminary data suggest that these three novel human polyomaviruses seem not to play a significant role neither in the pathogenesis of cutaneous malignancies nor in that of inflammatory disorders but, according to literature, can inhabit the skin. On the basis of our data regarding the HPyV6 DNA presence with decreasing percentages in healthy subjects, skin cancer and inflammatory disorders patients, it could be an intriguing matter to study if the activated innate immune response in inflammatory disorders can suppress the virus. Further investigations are needed to better understand their relationship with the human host and its innate immune system.

White blood cells, TNF-α, and interleukin-6 in subjects with infantile colic treated with Lacticaseibacillus rhamnosus GG (ATCC 53103): a randomised prospective study.

Recent metanalysis reported that certain probiotic strains, such as Limosilactobacillus reuteri and Lacticaseibacillus rhamnosus (LGG), seem effective for treatment of infantile colic of exclusively breastfed infants; some reports have also linked probiotics to have an immunological effect, however further investigation are needed to fully understand the exact mechanism. The objective of this study was to assay white blood cells, tumour necrosis factor (TNF)-α and interleukin (IL)-6 values in peripheral blood in subjects treated in a randomised, double-blind, placebo-controlled trial for infantile colic with LGG. Fifty-eight infants were enrolled and followed for a study period of 28 days. Parent were asked to record daily crying time using a structured cry diary. Peripheral white blood cells was assessed and RNA (mRNA) expression of TNF-α and IL-6 was measured using TaqMan real-time PCR-maternal amplification. Infants with colic treated with LGG showed a reduction in daily crying duration after 28 days of treatment and a reduction in values of IL-6 ( P < 0.005) and TNF-α ( P < 0.05); we observe also a significantly decreasing of IL-6 in the placebo group while decrease of TNF-α was not significant in this group. A significant decreased values of monocytes ( P < 0.05) was observed in infants treated with LGG. Our data therefore showed, in addition to crying time reduction, a significant decrease of TNF-α and a significant reduction of monocytes cells in colicky infants treated with LGG, compared to placebo group. This observation supports the hypothesis that probiotics may have anti-inflammatory properties. Further studies are needed to better understand the influence of probiotic on immunity cells.

Severe acute colitis related to levodopa treatment.

The first case of severe drug-induced gastrointestinal injury related to levodopa is described. The 86-year-old patient experienced acute colitis temporally related to the intake of the drug with complete resolution of symptoms on levodopa withdrawal. Awareness of the possibility of a levodopa-related damage on colon biopsies performed for acute colitis is of paramount importance for pathologists. However, in order to exclude or confirm a drug-related damage an effective communications between clinicians and pathologists is always required.

Regulatory T cells and Toll-like receptor 2 and 4 mRNA expression in infants with colic treated with Lactobacillus reuteri DSM17938.

Regulatory T cells induce immune homeostasis and the expression of Toll like receptors (TLRs); subsequent inflammatory cytokine release may be involved. Recent studies have shown a microbial imbalance in the gut of colicky infants (with a prevalence of gram-negative bacteria, such as Escherichia coli), and accumulating evidence has shown the efficacy of a probiotic (Lactobacillus reuteri) in breastfed subjects, but the underlying mechanism remains undefined. The study enrolled 59 infants younger than 60 days, of whom 34 subjects had colic and 25 were healthy controls. With a double-blind, placebo-controlled randomised study performed in our unit from October 2016 to July 2017, infants with colic were randomly assigned to receive oral daily L. reuteri DSM17938 (1×108 cfu) or placebo for 28 days. Peripheral blood was collected to assess the expression of FoxP3, TLR2 and TLR4 mRNA using real-time TaqMan RT-PCR at baseline and after the study period. Our findings showed increased mRNA expression of the transcription factor forkhead box P3 (FoxP3) in infants treated with L. reuteri DSM 17938 for 28 days (P<0.009) and increased TLR2 and TLR4 mRNA expression in both treated and placebo subjects. After L. reuteri administration for 28 days in infants with colic, we observed a significant decrease in daily crying time (302.3±19.86 min/day on day 0 vs 76.75±22.15 min/day on day 28, P=0.001). This study provides evidence that the observed increase in FoxP3 expression and reduction in crying time might be responses to probiotic treatment, while the increase in TLR2 and TLR4 mRNA expression might be related to age. Exploiting these new findings may lead to an unprecedented level of therapeutic control over immune tolerance using probiotics.

Role of vasoactive intestinal polypeptide (VIP) and endogenous somatostatin on the secretion of epidermal growth factor (EGF): studies on duodenal tissue cultures.

Epidermal Growth Factor (EGF)-containing cells have been found in Brunner's glands in the same area where several regulatory peptides are released. The present study was aimed at testing the release and the regulation of EGF secretion from cultured duodenal biopsies obtained from healthy individuals by gastroscopy. The effects and the interaction of VIP and somatostatin on the hormone release were studied. Duodenal biopsies were cultured at 37 degrees C in Mc Coy's buffer, gassed with 95% O2 and 5% CO2. After 30 min, the culture medium was decanted for the measurement of the hormones by RIA. To measure the protein content, the tissue was then homogenized; EGF detected in the culture was 11.5 ng/mg protein. The addition of VIP in the medium increased EGF mean levels to 21.6 ng/mg protein (P less than 0.01). The biopsies thus obtained were cultured with anti-somatostatin antibodies to evaluate the influence of endogenous somatostatin on EGF secretion. The inclusion of anti-somatostatin antibodies increased the EGF levels to 41.2 ng/mg protein (P less than 0.01). The combined addition of anti-somatostatin antibodies and VIP in the culture caused a mean EGF increase significantly higher than the values obtained separately by VIP and somatostatin (P less than 0.01). In conclusion, we can suggest a triangular interaction model of EGF release, where the somatostatin seems to be the negative monitor of over-secreted VIP and EGF from the gut.

Coexistence of different phenotypes in a family with glucocorticoid-remediable aldosteronism.

In glucocorticoid-remediable aldosteronism (GRA), there is a large interfamily variation of phenotype. We report three subjects with GRA in a single family (parents, two brothers and two sisters), of whom only one (proband) displayed classical features of the mineralocorticoid excess. The proband was a man found to be hypertensive and hypokalaemic at the age of 24 years. Plasma renin activity was suppressed and plasma aldosterone was repeatedly elevated. Blood pressure and aldosterone levels normalized within 5 days of dexamethasone therapy. The presence of a chimaeric CYP11B1/CYP11B2 gene was demonstrated by long-PCR and Southern blotting (crossover site at the end of intron 3) in the proband, in the younger sister (sibling 1) and in the father. In these patients, sequencing of the chimaeric portion of CYP11B1 did not reveal any mutation, while sequencing of the chimaeric portion of CYP11B2 showed a V386A polymorphism in exon 7, known to cause only a minimal impairment of enzymatic activity. Sibling 1 was normotensive, normokalaemic and had normal PRA and aldosterone. The father had normal blood pressure and potassium, low-normal PRA and normal aldosterone. All three subjects had elevated levels of urinary 18-hydroxycortisol and 18-oxocortisol. Baseline 11-deoxycorticosterone (DOC), corticosterone (B) and aldosterone were high in the proband and normal in the father and sibling 1; 11-deoxycortisol (S) and cortisol (F) were normal. ACTH induced a normal increase of B, DOC, S and F, and an excessive aldosterone increase in all three patients. Abnormalities in the chimaeric portions of CYB11B1 or CYP11B2 genes did not account for the phenotypic disparity of the different members in a single GRA family. Altered regulation of the chimaeric gene may be responsible for differences in its activity.

Thyroid volume in type 1 diabetes patients without overt thyroid disease.

An association between insulin-dependent diabetes mellitus (type 1) and thyroid diseases has long been reported, but the morphological evaluation of the thyroid in type 1 diabetes patients without overt thyroid disease has always been limited to physical examination. Ultrasonography of the thyroid gland was performed in 45 patients with type 1 diabetes without overt thyroid disease, to study thyroid volume and the prevalence of thyroid nodules. Data were compared with those obtained in 45 age- and sex-matched control subjects residing in the same area. In the patients, thyroid volume had increased on average by 46%; 35% of male and 32% of female patients had a thyroid volume exceeding the 95% confidence limits of the matched controls. The prevalence of thyroid nodules was only slightly raised. On average, free thyroxine was increased in the presence of normal triiodothyronine levels. Four patients were frankly hyperthyroid. The patients also showed a higher prevalence of thyroid-microsomal antibodies, but the thyroid hormone status was not different in relation to thyroid volume, nor was thyroid volume in relation to the presence of autoantibodies. Patients with type 1 diabetes without overt thyroid disorders may have morphological, ultrasonographically detectable alterations of the thyroid gland, the expression of a possible involvement of the thyroid in an autoimmune disorder not limited to the islet cells.

Color Doppler imaging study in patients with primary open-angle glaucoma treated with timolol 0.5% and carteolol 2%.

PURPOSE: To evaluate with color Doppler imaging (CDI), in patients with primary open-angle glaucoma (PDAG), the possible influence on ocular hemodynamics of a beta-blocking agent with intrinsic sympathomimetic acitivity (carteolol 2%) compared to a beta-blocker agent without this activity. METHODS: A study was carried out on 20 patients, with bilateral POaG, intraocular pressure (IOP) < or = 20 mmHg, all treated twice a day with timolol maleate 0.5% ophthalmic solution. The visual field was evaluated (Octopus 2000 perimeter, G1 program) examining the mean sensitivity (MS) and the mean defect (MD). CDI was carried out to evaluate the resistance index of the internal carotid artery (ICA), the ophthalmic artery (OA), the central retinal artery (CRA), and the short posterior ciliary arteries (SPCA). After these examinations, the therapy was changed to carteolol 2% twice a day. After six months of treatment the examinations were repeated. The data were analysed statistically using Student's t test. RESULTS: The mean intraocular pressure during treatment with timolol 0.5% was 16.7 +/- 1.67 mmHg and 16.33 +/- 1.72 mmHg after treatment with carteolol 2%, the difference not being significant (p=0.494). After six months of treatment with carteolol 2% the MS increased significantly from 22.4 +/- 2.5 dB to 24.1 +/- 1.8 dB (p=0.018), and the mean defect (MD) fell from 5.3 +/- 0.8 dB to 4.7 +/- 0.6 dB (p=0.011). There was no significant difference in the resistance index of the CA, the OA and the CRA with the two treatments, whereas the resistance index of the SPCA dropped significantly, from 0.80 +/- 0.05 to 0.77 +/- 0.02 (p = 0.017). CONCLUSIONS: CDI did not show significant differences in the resistance indexes of the internal CA, the OA, and the CRA after treatment with carteolol 2% but the resistance index of the SPCA was significantly reduced. Carteolol 2% induced significant changes in the perimetric indexes examined, with an increase in MS and a decrease in MD. These findings suggest that the intrinsic sympathomimetic activity of carteolol may reduce peripheral vascular resistance of the SCA, thus improving perfusion of the optic nerve head, with a protective effect on visual function.

[Bile acids in chronic hepatopathies]. / Gli acidi biliari nelle epatopatie croniche.

The clinical value of measuring biliary acids in various chronic liver disease was investigated. The sample examined included 17 healthy subjects, 16 patients with active chronic hepatitis, 15 with cirrhosis of the liver and 14 with cholestatic cirrhosis. The following parameters were considered in each patient: blood bilirubin, gamma GT, alkaline phosphatase, cholinesterase, blood cholesterol, Quick time. The total pool of biliary acids was assayed by the enzymatic method on samples taken in the morning before breakfast and two hours after intake of 600 mg ursodeoxycholic acid. Total biliary increased with the progression of the pathological condition. Unlike all other indicators biliary acid assays after oral loading with ursodeoxycholic acid makes it possible to distinguish between subjects with active chronic hepatitis and those with cirrhosis of the liver.

[Incidence of giardiasis in adults patients with acute enteritis]. / Incidenza della giardiasi in pazienti adulti con enterite acuta.

The Authors report the findings of a perspective study carried out in 214 cases of acute diarrhoea to estimate the presence of giardia intestinalis infections. The incidence of 3.2% has been discussed on the bases of recent epidemiological advances.

[Zinc and lymphocyte subsets in patients with HIV infection]. / Zinco e assetto linfocitario in pazienti con infezione da HIV.

Serum zinc levels were assayed in patients with AIDS and related syndromes, using spectrophotometry and atomic absorption. Statistical data have shown that serum zinc levels, in addition to being significantly lower (p less than 0.001) among different groups and controls, decrease progressively with the worsening of the clinical and immunological picture from LAS to AIDS. Serum zinc levels in patients with AIDS and ARC have, moreover, been demonstrated to be related (r = 0.8240; p less than 0.001) to the lymphocyte subset CD4 helper-induced. These results suggest that serum zinc determination and possibly zinc therapy might be reasonably considered in the management of patients with symptoms of HIV infection.

Modulation of cholinergic profile of acetylcholine through its cyclovinylogues.

The o-, m- and p-acetoxymethyl-N,N,N-trimethylbenzenemethanaminium iodide (2a-c) as cyclovinilogues of acetylcholine are described. This structural modification allows to modulate the cholinergic activity of the natural neurotransmitter along the sequence: agonist----partial agonist----antagonist, which is referred to meta (2b), para (2c) and ortho (2a) regioisomers, respectively.

[Effectiveness of nasal positive pressure ventilation in the management of acute refractory left ventricular insufficiency]. / Utilità ed efficacia della ventilazione a pressione positiva con maschera nasale nel trattamento dell'insufficienza ventricolare sinistra acuta refrattaria.

BACKGROUND: Ehen refractory to optimal medical treatment cardiogenic pulmonary edema requires mechanical ventilation as a last therapeutic resource. In recent years an increasing number of authors reported their experience in the management of acute or subacute respiratory failure with non-invasive mechanical ventilation by nasal mask. MATERIALS AND METHODS: Encouraged by the first promising results reported in literature we experimented this new therapeutic tool in a first group of seven elderly patients (mean age: 76.57--range: 65-89); they all had been admitted for severe cardiogenic pulmonary edema unresponsive to maximal doses of the conventional drugs available for treating acute decompensated heart failure. The enrolled patients were treated with intermittent ventilation administered by nasal mask at selected values of inspiratory positive airway pressure (IPAP) that were comprised between 10 and 20 cm H2O. At the same time an expiratory positive airway pressure (EPAP) at values comprised between 3 and 8 cm H2O was applied. Ventilation was continued for variable periods of 3-24 hours until acceptable values of PaO2 and PaCO2 were obtained. The ventilation modality was spontaneous, spontaneous-time or timed depending on the patients' level of consciousness at starting time. RESULTS: A good short-term outcome was achieved in all the patients regardless of the ventilation modality applied. The main blood gas alteration was severe hypercapnia with acidosis in three patients, while the other four presented critical hypoxemia unresponsive to simple oxygen supply even if delivered by high-flow Venturi mask. Four of our seven patients were discharged from hospital in satisfactory haemodynamic conditions; the remaining three died during hospitalization from refractory heart failure. CONCLUSIONS: In this our preliminary experience the therapeutic approach with nasal positive pressure ventilation (NPPV) and EPAP proved to be very effective to improve the signs and symptoms of acute refractory cardiogenic pulmonary edema as it avoided the need of invasive mechanical ventilation. It was well tolerated by all our patients; besides it was not difficult to use or time-consuming for physician and nurses. On the other hand it didn't modify our patients' medium or long-time prognosis which was strictly related to their preexisting left ventricular pump derangement.

[Effects of timolol maleate on untreated contralateral eyes (author's transl)]. / Effets du maléate de timolol sur l'oeil controlatéral sans traitement.

The efficacity of installations of 0,5 p. cent timolol maleate unilaterally was statistically evaluated in 15 subjects: 5 with open-angle glaucoma, 5 with secondary glaucoma, and 5 normal subjects. A reduction in intraocular pressure was observed in all cases, not only in treated eyes, but also, though to a lesser degree, in untreated eyes. Effects were almost totally lacking on lacrimal secretion, corneal sensitivity, and pupil size in both eyes. The hypothesis is raised of possible unilateral treatment in selected patients with ocular hypertension and/or trabecular glaucoma.

[Recovery of pump function in ischemic hypokinetic cardiopathy subjects treated with weekly intermittent infusion of dobutamine. A clinical case]. / Recupero della funzione di pompa in soggetto con cardiopatia ipocinetica ischemica trattata con dobutamina in infusione intermittente settimanale. Un caso clinico.

The case is reported of a 69-year-old man with refractory heart failure due to ischemic cardiomyopathy. All other available treatments having failed and 250 mg doses of furosemide having been administered without success, dobutamine infusion was tried, at first with 72 hours of continuous infusion of 5 mcg/kg/min, followed by intermittent infusion at the same dosage, first with 12-h intervals, subsequently at the rate of 2-3 infusions weekly, and finally, after about 50 days, with a single weekly infusion. Clinical and hemodynamic results were brilliant with the patient passing from grade IV NYHA to grade II and from ejection fraction 21% (Teichholz M-mode measurement) to 55%, 14 months after the start of dobutamine treatment. Discussing the possible mechanisms of this favourable result, the authors stress the possible improvement of the contractility of the "stunned" or "hibernating" myocardial segments. On the basis of their experience and of data in the literature the authors underline the validity of a therapeutic protocol of intermittent dobutamine infusion for severe heart failure.