A potentiometric and spectrofluorimetric approach to unravel inhibitory effects of semi- and thiosemicarbazones on mushroom tyrosinase activity.

The inhibitory effects on mushrooms tyrosinase activity of some semi- and thiosemicarbazones were investigated. While the semicarbazones are inactive, the thiosemicarbazones are, in general, more active than the reference (kojic acid, IC50 = 70 µM), with maximum activity obtained with benzaldehyde thiosemicarbazone (IC50 = 7 µM). These inhibitors probably act by coordination of the copper(II) metal ions in the active site of tyrosinase: effectively, potentiometric studies conducted in water solutions confirm that the most active thiosemicarbazone is a good ligand for copper(II) ions. The tyrosinase CD spectra do not show any significant difference by addition of an inhibitor or an inactive compound. On the contrary, interesting results were obtained by spectrofluorimetric titrations of mushrooms tyrosinase aqueous solutions with some of the investigated compounds, giving helpful information about possible mechanism of action. The thiosemicarbazones here reported are not cytotoxic on human fibroblasts and do not activate cells in a pro-inflammatory way.

Multidimensional Short Tools to assess frailty: a narrative review.

Background: The population of the European Union is progressively ageing, therefore frailty is becoming a crucial public health issue. In recent years there is a growing interest in a multidimensional concept of frailty, that is not only physical but also psychological and social, in line with a person-centered care. Study design: To measure frailty represents a fundamental step to evaluate the needs for care at both population and individual levels. Of course, to assess frailty in a large population is essential to find short and quick tools able to give reliable results in terms of risk of occurrence of negative events, to stratify older adults according to their frailty level. In this way the most appropriate strategies can be chosen and applied, to delay the functional decline associated to frailty and its consequences, such as hospitalization, institutionalization, low quality of life, and death. Methods: In this review we searched on PubMed for articles about scales assessing frailty with peculiar characteristics: published for the first time in 2010, available in English, with a short length and duration of administration, composed by multidimensional domains. Results: Seven scales were found and analyzed: The Zulfiqar Frailty Scale (ZFS), The Pictorial Fit-Frail Scale (PFFS), The Tilburg Frailty Indicator (TFI), The SUNFRAIL Tool, The (fr)AGILE, The Risk Instrument for Screening in the Community (RISC) and The Short Functional Geriatric Evaluation (SFGE). We compared their main features as the number of questions, the time for administration, the domains used and the psychometric properties as validity and reliability, with the aim of providing a set of useful information to health professionals in their everyday work. Conclusions: The use of these tools provides important information to help plan community health and social care and meet individuals' needs for care, but this approach is not common for community care in the EU yet.

In response to the Letter to the Editor by Dr AA. Zulfiqar re our publication "Multidimensional Short Tools to Assess Frailty: a Narrative Review" (Ann Ig. 2022 Mar 18. doi: 10.7416/ai.2022.2516. Online ahead of print).

Abstract: We appreciate that Dr. Zulfiqar showed us that they had already demonstrated the validity and reliability of his ZFS scale. Still, it is evident that, in our paper, we could not take it for granted because all the articles they quote have been published after we handed out ours to the Managing Editor of Ann Ig.

The effect of community nurse on mortality and hospi- talization in a group of over-75 older adults: a nested case-control study.

Background: Bio-psycho-social frailty can negatively affect the health status of an ageing population. The integration between community nurses and social services can emphasize community care and prevent the onset of both health and social negative outcomes in the older population. The aim of the paper is to explore the causal association through the analysis of the hospitalization and mortality rate after a pro-active social service integrated by the community nurse. Study Design: A nested case-control study comparing groups of older adults has been carried out. Methods. The paper compares data stem from a cohort followed up by the University of Rome "Tor Vergata" with data from the "Long Live the Elderly!" program (LLE) cohort. Results: One-year standardized mortality rate was 6.5%, 4.7% and 7.5% in the control group, the LLE group and the LLE group integrated by the community nurse (LLE-CN), respectively. One-year hospitalization rate was 15.4%, 15.5% and 10.8% in the control group, the LLE group and the LLE-CN group, respectively. Conclusions: According to our results a social service with a pro-active approach, integrated by the community nurse, appears to be able to reduce mortality and hospitalization in a group of older adults aged>75. The multidimensional assessment of frailty stands for the first step of a new organization of community services.

From the bench to practice - Field integration of community-based services for older citizens with different levels of functional limitation across European Regions.

The meeting of the European Innovation Partnership on Active and Healthy Ageing (EIPonAHA) action group A3 together with members of the Reference site collaborative network (RSCN) in December 2019 in Rome focused on integration of evidence-based approaches on health and care delivery for older citizens at different levels of needs with expertise coming from stakeholder across Europe. It was the final aim of the group to co-create culturally sensitive pathways and facilitate co-ownership for further implementation of the pathways in different care systems across Europe. The study design is a mixed method approach. Based on data analysis from a cohort of community-dwelling over-65 citizens in the framework of a longitudinal observational study in Rome, which included health, social and functional capacity data, three personas profiles were developed: the pre-frail, the frail and the very frail personas. Based on these data, experts were asked to co-create care pathways due to evidence and eminence during a workshop and included into a final report. All working groups agreed on a common understanding that integration of care means person-centered integration of health and social care, longitudinally provided across primary and secondary health care including citizens' individual social, economic and human resources. Elements for consideration during care for pre-frail people are loneliness and social isolation, which, lead to limitation of physical autonomy in the light of reduced access to social support. Frail people need adaption of environmental structures and, again, social resource allocation to maintain at home. Very frail are generally vulnerable patients with complex needs. Most of them remain at home because of a strong individual social support and integrated health care delivery. The approach described in this publication may represent a first approach to scaling-up care delivery in a person-centered approach.

The effect of maternal intake of sucrose or high-fructose corn syrup (HFCS)-55 during gestation and lactation on lipogenic gene expression in rat offspring at 3 and 12 weeks of age.

Perinatal exposure to sucrose or high-fructose corn syrup-55 (HFCS-55) in rats has previously been associated with altered hepatic fat content and composition post-weaning, although the effects on hepatic metabolism are unknown. The current study aimed to determine the sex-specific effects of maternal consumption of sucrose or HFCS-55 on the expression of hepatic lipogenic genes in the offspring. Liver samples were collected from offspring of albino Wistar rats provided with ad libitum access to either water (control), 10% sucrose or 10% HFCS-55 solution during pregnancy and lactation at 3 weeks (control n=16, sucrose n=22, HFCS-55 n=16) and 12 weeks (control n=16, sucrose n=10, HFCS-55 n=16) of age. Hepatic expression of the transcription factors such as carbohydrate response element-binding protein, sterol regulatory element-binding protein-1c and downstream genes was determined by quantitative real-time PCR. Sucrose-exposed offspring had higher hepatic SREBP-1c messenger RNA expression compared with control and HFCS-55 groups at both 3 weeks (P=0.01) and 12 weeks (P=0.03) of age. There were no differences in the expression of other hepatic lipogenic genes between groups at either 3 or 12 weeks. Thus, perinatal exposure to sucrose may be more detrimental to offspring hepatic metabolism compared with HFCS-55, independent of sex, and it will be important to evaluate the longer-term effects of perinatal sucrose exposure in future studies.

Maternal nutrient restriction in early pregnancy programs hepatic mRNA expression of growth-related genes and liver size in adult male sheep.

The liver is a major metabolic and endocrine organ of critical importance in the regulation of growth and metabolism. Its function is determined by a complex interaction of nutritionally regulated counter-regulatory hormones. The extent to which hepatic endocrine sensitivity can be programed in utero and whether the resultant adaptations persist into adulthood is unknown and was therefore the subject of this study. Young adult male sheep born to mothers that were fed either a control diet (i.e.100% of total live weight-maintenance requirements) throughout gestation or 50% of that intake (i.e. nutrient restricted (NR)) from 0 to 95 days gestation and thereafter 100% of requirements (taking into account increasing fetal mass) were entered into the study. All mothers gave birth normally at term, the singleton offspring were weaned at 16 weeks, and then reared at pasture until 3 years of age when their livers were sampled. NR offspring were of similar birth and body weights at 3 years of age when they had disproportionately smaller livers than controls. The abundance of mRNA for GH, prolactin, and IGF-II receptors, plus hepatocyte growth factor and suppressor of cytokine signaling-3 were all lower in livers of NR offspring. In contrast, the abundance of the mitochondrial protein voltage-dependent anion channel and the pro-apoptotic factor Bax were up regulated relative to controls. In conclusion, maternal nutrient restriction in early gestation results in adult offspring with smaller livers. This may be mediated by alterations in both hepatic mitogenic and apoptotic factors.

Hepatotoxicity induced by greater celandine (Chelidonium majus L.): a review of the literature.

The available literature assessing Chelidonium majus L. (CM) hepatotoxicity potential, and its risk to benefit assessment has been reviewed in this paper. Identification of significant scientific literature was performed via the following research databases: Cochrane Central, Google Scholar, EMBASE, Medline, Science Direct, Scopus, Web of Science, using the following keywords: "Chelidonium majus", "greater celandine", "Hepatotoxicity", "Liver" "Injury", "Toxicity" individually investigated and then again in association. CM named also greater celandine, swallow-wort, or bai-qu-cai (Chinese), has been used for a long time in traditional Chinese medicine and phytotherapy. Its extracts have been claimed to display a wide variety of biological activities: antimicrobial, anti-inflammatory, spasmolytic, antineoplastic, hepatoprotective, and analgesic. Moreover, herbal medicine suggests this plant have numerous additional effects which have not yet been scientifically evaluated, such as antitussive, diuretic, and eye-regenerative. However, despite its claimed hepatoprotective effects, several hepatotoxicity cases have been reported to be probably or highly probably connected with CM exposure, after their evaluation through liver-targeted causality assessment methods. CM hepatotoxicity has been defined as a distinct form of herb-induced liver injury (HILI), due to an idiosyncratic reaction of the metabolic type. This evidence has to be considered in relationship with the absence of considerable benefits of CM therapy. Therefore, the risk to benefit ratio of the use of herbal products containing greater celandine can actually be considered as negative.

Effect of a p210 multipeptide vaccine associated with imatinib or interferon in patients with chronic myeloid leukaemia and persistent residual disease: a multicentre observational trial.

BACKGROUND: Although imatinib is the standard treatment for chronic myeloid leukaemia, not all patients reach complete cytogenetic remission (CCR) and most maintain detectable disease at the molecular level. We investigated whether a vaccine targeting the BCR-ABL-derived p210 fusion protein was an active and specific immunotherapy. METHODS: We recruited 16 patients who had chronic myeloid leukaemia (with the b3a2 fusion point of p210), stable residual disease, a minimum treatment of 12 months of imatinib or 24 months of interferon alfa, and no further reduction of residual disease for at least 6 months preceding enrollment. They were given six vaccinations with a peptide vaccine derived from the sequence p210-b3a2 plus molgramostim and QS-21 as adjuvants (CMLVAX100) before assessment of immunological and disease response, which included detecting amounts of b3a2 transcripts by standardised quantitative real-time reverse-transcriptase PCR. RESULTS: Of ten patients on imatinib, nine started CMLVAX100 having had a median of 10 months' stable cytogenetic disease (median 10% Philadelphia-chromosome-positive metaphases), whereas one started in stable CCR. All patients' cytogenetic responses improved after six vaccinations, with five reaching CCR. Notably, three of these five patients also had undetectable amounts of b3a2 transcript (BCR-ABL:beta2 microglobulin ratio <0.00001). Six patients on interferon alfa treatment with a median of 17 months' stable residual disease (median 13% Philadelphia-chromosome-positive cells) were also vaccinated. All but one had improved cytogenetic responses, and two reached CCR. Overall, we recorded peptide-specific delayed-type hypersensitivity (in 11 of 16 patients), CD4 cell proliferation (13 of 14 assessed), and interferon gamma production (five of five assessed). INTERPRETATION: Addition of CMLVAX100 to conventional treatment in patients with chronic myeloid leukaemia might favour further reduction of residual disease and increase the number of patients reaching a molecular response.

The effect of maternal and post-weaning low and high glycaemic index diets on glucose tolerance, fat deposition and hepatic function in rat offspring.

Clinical studies have reported beneficial effects of a maternal low glycaemic index (GI) diet on pregnancy and neonatal outcomes, but the impact of the diet on the offspring in later life, and the mechanisms underlying these effects, remain unclear. In this study, Albino Wistar rats were fed either a low GI (n=14) or high GI (n=14) diet during pregnancy and lactation and their offspring weaned onto either the low or high GI diet. Low GI dams had better glucose tolerance (AUC[glucose], 1322±55 v. 1523±72 mmol min/l, P<0.05) and a lower proportion of visceral fat (19.0±2.9 v. 21.7±3.8% of total body fat, P<0.05) compared to high GI dams. Female offspring of low GI dams had lower visceral adiposity (0.45±0.03 v. 0.53±0.03% body weight, P<0.05) and higher glucose tolerance (AUC[glucose], 1243±29 v. 1351±39 mmol min/l, P<0.05) at weaning, as well as lower hepatic PI3K-p85 mRNA at 12 weeks of age. No differences in glucose tolerance or hepatic gene expression were observed in male offspring, but the male low GI offspring did have reduced hepatic lipid content at weaning. These findings suggest that consuming a low GI diet during pregnancy and lactation can improve glucose tolerance and reduce visceral adiposity in the female offspring at weaning, and may potentially produce long-term reductions in the hepatic lipogenic capacity of these offspring.

Consumption of sucrose, but not high fructose corn syrup, leads to increased adiposity and dyslipidaemia in the pregnant and lactating rat.

Excess consumption of added sugars, including sucrose and high fructose corn syrup (HFCS-55), have been implicated in the global epidemics of obesity and type 2 diabetes. This study aimed to investigate and compare the impact of maternal consumption of sucrose or HFCS-55 during pregnancy and lactation on the metabolic health of the dam and her offspring at birth. Female Albino Wistar rats were given access to chow and water, in addition to a sucrose or HFCS-55 beverage (10% w/v) before, and during pregnancy and lactation. Maternal glucose tolerance was determined throughout the study, and a postmortem was conducted on dams following lactation, and on offspring within 24 h of birth. Sucrose and HFCS-55 consumption resulted in increased total energy intake compared with controls, however the increase from sucrose consumption was accompanied by a compensatory decrease in chow consumption. There was no effect of sucrose or HFCS-55 consumption on body weight, however sucrose consumption resulted in increased adiposity and elevated total plasma cholesterol in the dam, while HFCS-55 consumption resulted in increased plasma insulin and decreased plasma non-esterified fatty acids (NEFA). Maternal HFCS-55 consumption was associated with decreased relative liver weight and plasma NEFA in the offspring at birth. There was no effect of either treatment on pup weight at birth. These findings suggest that both sucrose and HFCS-55 consumption during pregnancy and lactation have the potential to impact negatively on maternal metabolic health, which may have adverse consequences for the long-term health of the offspring.

Age and blood pressure changes. A 20-year follow-up study in nuns in a secluded order.

In a prospective study, 144 white nuns belonging to a secluded monastic order and 138 white control laywomen were followed for 20 years to investigate whether living for a long time in a stress-free environment influences the effect of aging on blood pressure. Silence, meditation, and isolation from society are the distinctive features of the life-style examined. At study entry, blood pressure was not dissimilar in the nuns and the control group, but it increased over time only in the controls, with a mean slope of the regression line (beta coefficient) of 0.089 in the nuns (NS) and 2.171 in the controls (p less than 0.0001) for systolic blood pressure and of 0.054 in the nuns (NS) and 0.742 in the controls (p less than 0.0001) for diastolic blood pressure. Weight and body mass index increased similarly over time in the two groups. Family history of hypertension was not dissimilar between the groups. Serum cholesterol and triglycerides, higher at study entry in the nuns, increased similarly over time in the two groups. Twenty-four-hour urinary sodium excretion, collected randomly in both groups, did not differ over time between nuns and controls. None of the women smoked or used oral contraceptives. Educational level was higher in the control group, but subgroups of 48 nuns and 52 laywomen of comparable educational level maintained the same difference in the blood pressure trend over time as in the main cohort. Parity affected the increase of systolic, but not of diastolic, blood pressure with age among the laywomen, but nuns and no-childbirth controls maintained a significantly different blood pressure trend over time.(ABSTRACT TRUNCATED AT 250 WORDS)

Mitochondrial aspartate aminotransferase isoenzyme: a biochemical marker for the clinical management of alcoholics?

Serum mitochondrial and total aspartate aminotransferase activity was quantified by a characterized immunochemical method in 126 subjects, 44 healthy controls and 82 chronic alcoholics (51 outpatients and 31 monitored through 15 days). The monitored alcoholics were divided into actual abstinents (n = 21) and drinkers (n = 10) by blood ethanol concentration performed daily. The aims of the present study were: (a) to compare the diagnostic diagnostic usefulness of the mitochondrial isoenzyme and the mitochondrial/total aspartate aminotransferase ratio to detect problematic drinkers; (b) to evaluate the suitability of these indices to monitor abstinence, a difficulty not yet solved in the clinical management of alcoholics. The results demonstrated the mitochondrial isoenzyme to be more suitable to discriminate between controls and alcoholics (Kruskal and Wallis ANOVA, Bonferroni test, P < 10(-5) and mostly between actual drinkers and other alcoholics (P < 0.041). So acute alcohol consumption may be a significant, suggestive and until now inadequately examined factor in evaluating the suitability of mAST as a marker. The results, showing that mAST peaks quickly appear in the presence of a new alcohol intake, should indicate mAST as a possible marker of acute alcohol intake useful in checking self-claimed abstinence.

Rapid onset of (R)-alpha-methylhistamine protection in response to ethanol-induced histologic damage in rat gastric mucosa.

The influence of pretreatment with (R)-alpha-methylhistamine, selective agonist of histamine H3 receptors, has been investigated on gastric mucosal lesions at different time intervals, from 5 to 60 minutes, after administration of absolute ethanol in the rat. The amount and depth of lesions were quantitatively evaluated by light microscopy. In rats pretreated with (R)-alpha-methylhistamine, the integrity of the mucosa was preserved in approximately 80% of the total mucosal length measured despite ethanol challenge. Prevention of lesion formation was as great at 5 min after ethanol administration as at 60 min. When present, damage involved mainly superficial mucosa and lesions extending deeply into the gland region were evident in 1-2.5% of the total mucosa. Present findings indicate that mechanisms by which (R)-alpha-methylhistamine operates enable the mucosa to counteract damage just from the moment of exposure to ethanol and that protection is exerted both on surface and pit cells and on gastric glands.

Prognostic value of brainstem auditory evoked potentials in pediatric patients with traumatic coma.

This paper studies the auditory evoked potentials of the brainstem (BAEPs) in 30 pediatric patients with serious head trauma admitted to a particular hospital. The results have shown the importance of BAEPs especially in those patients whose prognoses are uncertain.

Thymostimulin effect on the immune response in neoplastic patients submitted to surgical treatment.

We selected the data from performance status, disease state, skin tests, circulating lymphocytes and relative subsets, serum immunoglobulin classes to evaluate the immune response in 29 neoplastic patients treated with surgery and undergoing Thymostimulin administration during long term follow-up. Moderate drug intolerance was observed in 3 patients. After treatment lymphocyte count increase (41% mean increase) in 61.5% of cases; CD3, CD4, CD8, CD16 respectively 95-74-87-82% of cases; immunoglobulin classes in about 90% of cases. A clear-cut improvement of Karnofsky's index was observed in 34.6% of cases, worsening in 11.5%. A manifest improvement in the delayed hypersensitivity skin test resulted in 36% of cases. Most patients (85%) have shown signs of complete disease remission. Disease progression was observed only in 3 patients. There were no infections during this study.

Thymostimulin effect on the immune response in pulmonary carcinoma with or without surgical treatment.

Experience with 54 patients affected by pulmonary carcinoma treated or not with surgery and undergoing thymostimulin administration during long-term follow-up (70 mg i.m. every other day for 3 months), is reported. Drug intolerance was observed in 5.5% of cases. In patients who were able to complete the therapeutic cycle (50 cases) objective improvement of Performance Status was obtained in 46% of cases and subjective improvement in nearly 90%. The course of neoplastic disease showed definite progression (presence of local recurrence or distant metastasis) in 20% of cases, remission in 6%. No case of onset of pulmonary or extrapulmonary infections was observed. After treatment, a significant increase (between 24% and 108%) in blood parameters (circulation lymphocytes, CD3, CD4, CD8, CD16, IgG, IgA, IgM) was observed in 28-56% of cases. As for CD4 increase, this was accompanied by concomitantly positive Merieaux test in 44.5% of cases. Quiescence or complete remission has appeared to occur together with high CD16 values, progression with high CD8 and low CD16 values.

Carcinoma of the duodenum: management and survival in 14 cases.

AIMS: The aim of this study is to evaluate the role of surgery in the treatment of adenocarcinoma of the duodenum. METHODS: From 1955 to 1994, 14 patients with primary adenocarcinoma of the duodenum underwent surgical treatment in our department. Presenting signs and symptoms were mainly related to obstruction and bleeding. Upper gastrointestinal contrast study, Computed Tomography (CT) and duodenoscopy were the primary diagnostic procedure modalities. All diagnoses were confirmed histologically. The tumors were staged pathologically according to the new TNM classification (UICC, 1992). Eight patients received palliative treatment or exploratory laparotomy. The remaining 6 patients were resectable for cure. RESULT: Operative mortality was 35.7%. The 5-year survival rate for patients who underwent curative resection was 33.3%. None of the patients who underwent palliative procedures or exploratory laparotomy survived for more than 11 months. CONCLUSIONS: In the management of resectable adenocarcinomas of the duodenum surgical radicality including lymphadenectomy should be pursued. Unresectable adenocarcinomas treated with palliative procedure had a very poor prognosis.