Haematology and biochemistry in healthy llamas at sea level.

In the last years, there has been an increasing interest in llamas, not only as part of a productive system, but mostly as companion animals. Most reports regarding clinical biochemistry and haematology include few llamas and details about their health status are not available. The present study aims to provide haematological and biochemical parameters for llamas of known health status. Twenty-three non-pregnant females and seven males that live in Buenos Aires, Argentina (34°36'S, 58°22'W, at sea level) were studied. Llamas were clinically healthy, in good nutritional status. Animals were kept at grass and were fed hay bale or pellets and water ad libitum. Blood samples were collected by jugular venipuncture in spring. Packed cell volume, leucocyte count, differential white cell count, platelets count, urea, creatinine, total proteins, albumin, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, glucose, calcium and phosphate were assessed. No significant differences were observed between males and females, except for platelet count and calcium, which was greater in males (P˂0.01). Values obtained for the different parameters were similar to those previously reported, except for monocytes, alkaline phosphatase, glucose and calcium, that were lower and lymphocytes and platelets count, that were higher in this study. In conclusion, different ambient and methodological conditions might affect some parameters. The parameters hereby presented are representative of llama's population living at sea level in South America.

Major adverse cardiovascular events associated with VEGF-targeted anticancer tyrosine kinase inhibitors: a real-life study and proposed algorithm for proactive management.

BACKGROUND: Vascular endothelial growth factor receptor (VEGFR)-targeted tyrosine kinase inhibitors (TKIs) are widely used in cancer treatment and burdened by cardiovascular toxicity. The majority of data come from clinical trials, thus in selected populations. The aim of our study is to evaluate the cardiotoxicity profile of VEGFR-targeted TKIs and the impact of cardiovascular risk factors in a real-life population. PATIENTS AND METHODS: In this cohort, population-based study, patients treated with VEGFR-targeted TKIs, bevacizumab and trastuzumab between 2009 and 2014 were analyzed. A multi-source strategy for data retrieval through hospital, pharmaceutical and administrative databases of the Lombardy region, Italy, has been adopted. The primary endpoint was to determine the incidence and type of major adverse cardiovascular events (MACEs) along with their temporal trend. The secondary endpoint was to define the impact of cardiovascular risk factors in the occurrence of MACEs. RESULTS: A total of 829 patients were treated with VEGFR-targeted TKIs. Eighty-one MACEs occurred in the first year of follow-up [crude cumulative incidence (CCI): 9.79%] mainly consisting of arterial thrombotic events (ATEs, 31 events, CCI: 3.99%), followed by rhythm disorders (22 events, CCI: 2.66%), pulmonary embolisms and heart failures (13 events each, CCI: 1.57%). While the incidence of most MACEs showed a plateau after 6 months, ATEs kept increasing along the year of follow-up. Hypertension and dyslipidemia were associated with an increase in risk of ATEs [relative risk difference (RRD) +209.8% and +156.2%, respectively], while the presence of previous MACEs correlated with a higher risk of all MACEs in multivariate analysis (RRD 151.1%, 95% confidence interval 53.6% to 310.3%, P < 0.001). CONCLUSIONS: MACEs occur in a clinically significant proportion of patients treated with VEGFR-targeted TKIs, with ATEs being predominant, mainly associated with hypertension and dyslipidemia. A clinical algorithm for effective proactive management of these patients is warranted.

Receptor-mediated signaling in Aspergillus fumigatus.

Aspergillus fumigatus is the most pathogenic species among the Aspergilli, and the major fungal agent of human pulmonary infection. To prosper in diverse ecological niches, Aspergilli have evolved numerous mechanisms for adaptive gene regulation, some of which are also crucial for mammalian infection. Among the molecules which govern such responses, integral membrane receptors are thought to be the most amenable to therapeutic modulation. This is due to the localization of these molecular sensors at the periphery of the fungal cell, and to the prevalence of small molecules and licensed drugs which target receptor-mediated signaling in higher eukaryotic cells. In this review we highlight the progress made in characterizing receptor-mediated environmental adaptation in A. fumigatus and its relevance for pathogenicity in mammals. By presenting a first genomic survey of integral membrane proteins in this organism, we highlight an abundance of putative seven transmembrane domain (7TMD) receptors, the majority of which remain uncharacterized. Given the dependency of A. fumigatus upon stress adaptation for colonization and infection of mammalian hosts, and the merits of targeting receptor-mediated signaling as an antifungal strategy, a closer scrutiny of sensory perception and signal transduction in this organism is warranted.

Diabetes mellitus and the risk of prostate cancer in Italy.

OBJECTIVE: We investigated the relation between diabetes and the risk of prostate cancer, as epidemiological results are controversial. METHODS: A hospital-based case-control study was conducted in Italy between 1991 and 2002. Cases were 1294 men, aged <75 years, with incident histologically confirmed prostate cancer, and controls were 1451 men, aged <75 years, admitted to hospital for acute non-neoplastic diseases. Odds ratios (OR) and the corresponding 95% confidence intervals (CI) were estimated using unconditional multiple logistic regression models. RESULTS: No material association between diabetes and prostate cancer was observed, with a multivariate OR of 1.02 (95%CI 0.75-1.40). Prostate cancer was not related to time since diagnosis of diabetes (OR 0.82 and 0.97 for <5 and >/=15 years since diagnosis respectively). The OR were respectively 1.63 (95%CI 0.70-3.81) and 0.96 (95%CI 0.68-1.34) in men diagnosed with diabetes at age <45 or >/=45 years. The risk estimates were similar across strata of age at interview, body mass index and, among cases, of Gleason score. CONCLUSIONS: This study shows no material association between diabetes and prostate cancer risk.

Fiber intake and risk of nonfatal acute myocardial infarction.

OBJECTIVE: To investigate the association between fiber intake and risk of acute myocardial infarction (AMI), also according to type and source of fiber, in a Mediterranean country. DESIGN: Hospital-based case-control study. SETTING: Northern Italy. SUBJECTS: A total of 507 cases of first nonfatal AMI and 478 controls in hospital for acute conditions. INTERVENTIONS: Subjects were interviewed with a questionnaire that included a validated food frequency section. Odds ratios (OR) were obtained using multiple logistic regression, and adjusted for several recognized risk factors for AMI. Fiber was measured as non-starch polysaccharides. RESULTS: Compared with the lowest one, the OR in the highest tertile was 0.72 for total fiber, 0.64 for soluble fiber, 0.77 for total insoluble fiber, 0.71 for cellulose, 0.81 for insoluble non-cellulosic polysaccharides, 0.82 for vegetable fiber, 0.64 for fruit fiber and 1.11 for cereal fiber, and the estimates were statistically significant for soluble and fruit fiber. When further adjusted for beta-carotene, vitamin C and vitamin E intake, the fruit fiber still showed the strongest inverse relation, although the association was no longer significant. The protective effect of fiber was more marked in, or restricted to, subjects with other AMI risk factors, such as smokers, diabetics and hypertensives. CONCLUSIONS: Though an inverse association between fiber intake and AMI risk appears established, the causality of this association is still open to debate. In this population, cereal fiber derives chiefly from refined grains, and this may explain the lack of protection by this type of fiber.

Renal mechanisms involved in stress-induced antinatriuresis and antidiuresis in rats.

The present study was conducted to investigate if changes in sodium and water excretion in stressed animals were due to modifications in the glomerular filtration rate (GFR) and to determine the participation of angiotensin II (Ang II) and alpha and beta-adrenoceptors on sodium and water renal excretion in rats subjected to immobilization stress (IMO). Male Wistar rats (250-300 g) were randomly separated into five different groups and vehicle (0.9% NaCl) via intraperitoneal (i.p.) or propanolol (3 mg/kg i.p.) or captopril (6 mg/kg i.p.) or yohimbine (3 mg/kg i.p.) or prazosin (1 mg/kg i.p.) were injected respectively. During experimental measurements, the animals were kept in metabolic cages for 6 h and sodium, potassium and water renal excretion and saline (1.5% NaCl) and water intake were determined at day 1 (drug effect) and day 7 (drug + IMO effects). GFR was measured by creatinine clearance in control and IMO rats. A stress-induced antinatriuresis and antidiuresis was reversed by alpha 1 and alpha 2-adrenoceptor antagonists, while captopril inhibited only the antidiuresis and propranolol had no effect on either parameter. No differences were observed in creatinine clearance in the studied groups. Since yohimbine blocks alpha 2-adrenoceptors and prazosin blocks alpha 1-adrenoceptors and alpha 2B-adrenoceptors, the stress-induced renal sodium reabsorption mainly could be attributed to alpha 2B-adrenoceptors. The present results indicate that beta-adrenoceptors do not participate in this response and, Ang II only reverses the antidiuresis and shows a slight participation in antinatriuresis. The increment in sodium and water reabsorption caused by IMO occurred without changes in the glomerular filtration rate.

Physiological parameters and biodistribution of 5,10,15,20-tetra (4-methoxyphenyl) porphyrin in rats.

Physiological parameters on hepatic and renal functionality and biodistribution, accumulation and elimination, in different organs of the 5,10,15,20-tetra (4-methoxyphenyl) porphyrin (TMP) were determined in Wistar rats. The transport of TMP by low-density (LDL) and high-density lipoproteins (HDL) was also investigated. The photosensitizer is accumulated in the spleen, where its concentration is significantly increased 21 d post-injection; it also accumulates in the liver and in a lower proportion, in the duodenum, and poorly in brain and muscle. The urine and serum biochemical parameters reached normal values both in control and treated groups. The glomerular filtrate rate was not affected by the TMP treatment in any of the studied times. These results would indicate that the sensitizer does not modify the renal glomerular function. TMP is mainly eliminated from the organism via the bile-gut pathway. Considering the total amount of porphyrin bound to both lipoproteins (LDL and HDL) in comparison with the total value of the TMP in serum, it can be inferred that a large amount of the agent is transported by lipoproteins in the plasma. This study proves information about the behavior of TMP in vivo under dark conditions. The results can be used to design photodynamic treatments using this porphyrin model as the sensitizer.

Does coffee protect against hepatocellular carcinoma?

We analysed the relation between coffee consumption and hepatocellular carcinoma in two case-control studies conducted between 1984 and 1998 in Italy and Greece, including 834 cases and 1912 controls. Compared to non coffee drinkers, the multivariate odds ratio was 0.7 for drinkers of three or more cups per day.

Cancer of the larynx in non-smoking alcohol drinkers and in non-drinking tobacco smokers.

The separate effect of alcohol and tobacco on laryngeal cancer was analysed in two case-control studies from Italy and Switzerland, comprising 40 non-smoking and 68 non-drinking cases, and 160 non-smoking and 161 non-drinking controls. The multivariate odds ratio was 2.46 for heavy drinkers non-smokers, and 9.38 for current smokers non-drinkers.

n-3 Polyunsaturated fatty acids, fish, and nonfatal acute myocardial infarction.

BACKGROUND: The relation between n-3 polyunsaturated fatty acids (PUFAs), fish intake, and risk of coronary heart disease is controversial. METHODS AND RESULTS: An Italian case-control study including 507 patients with nonfatal acute myocardial infarction (AMI) and 478 hospital controls found a multivariate odds ratio (OR) of 0.67 (95% CI, 0.47 to 0.95) for the highest n-3 PUFA intake and 0.68 (95% CI, 0.47 to 0.98) for an intake of >1 portion of fish per week compared with >/=2 portions per week. CONCLUSIONS: Small amounts of n-3 PUFAs may be inversely related to AMI risk in this low-risk population.

Alcohol, smoking, coffee and risk of non-fatal acute myocardial infarction in Italy.

OBJECTIVES: To assess the relation between cigarette smoking, alcohol, coffee, decaffeinated coffee and tea consumption, and the risk of non-fatal acute myocardial infarction (AMI). DESIGN AND SETTING: Hospital-based case-control study conducted in 1995-1999 in Milan, Italy. PATIENTS: 507 cases with a first episode of non-fatal AMI, and 478 controls admitted to hospital for acute diseases. METHODS: Information was collected by interviewer-administered questionnaires. Odds ratios (OR) and 95% confidence intervals (CI) were calculated by multiple logistic regression. RESULTS: Compared to alcohol non-drinkers the OR was 0.6 (95% CI: 0.4-0.9) in drinkers, and 0.5 in drinkers of > 3 drinks/day. The OR for > 1 drink/day of wine was 0.5, and those for beer, amari, grappa and spirits ranged between 0.4 and 0.6. Compared to never smokers, the OR was 2.2 (95% CI: 1.5-3.1) among current smokers, and 4.6 among current smokers of > or = 25 cigarettes/day. The risk was similar to that of never smokers > or = 5 years after cessation (OR: 1.1 after 5-9 years, 0.7 after > or = 10 years). The OR was 2.3 for low tar cigarettes and 2.0 for high tar ones. The OR for coffee intake (expresso and mocha) was around unity up to 3 cups/ day, but rose to 1.9 (95% CI: 1.1-3.3) for > or = 6 cups/ day. Moderate decaffeinated coffee and tea intake was not associated with AMI risk. Compared to non-smokers drinking < or = 3 cups of coffee/day, the OR was 1.6 among non-smokers drinking > 3 cups of coffee/ day and 3.3 (95% CI: 2.1-5.0) among current smokers drinking < or = 3 cups of coffee/day. Compared to alcohol drinkers with a coffee intake of < or = 3 cups/ day, alcohol non-drinkers with higher coffee intake had an OR of 2.2, and compared to non-smokers alcohol drinkers, the OR was 3.3 in current smokers alcohol non-drinkers. CONCLUSIONS: In this Italian population alcohol intake was inversely associated to AMI risk, while smoking and heavy (but not moderate) coffee drinking increased the risk.

Renal excretion and saline intake during post-stress immobilization period in rats.

An experiment in which the rats access either to 0.5% or 1.5% saline was designed in order to further characterise the relationship between sodium intake and renal excretion after acute immobilization stress. A saline solution for 3 days was provided to the rats previous to the experimental day. On that day, after finishing acute immobilization stress, all variables under observation were measured every 6 h for 24 h. These periods were denominated as follows: T1 (12.00 to 18.00 h), T2 (18.00 to 24.00 h), T3 (24.00 to 06.00 h) and T4 (06.00 to 12.00 h). Acute immobilization stress reduced sodium renal excretion in both T1 and T2. Sodium intake in acute immobilization stress rats was lower than in control rats during all observed periods, while the urine volume was only reduced in the stressed animals in T1. These results were similar in both saline solution concentrations. A good correlation was observed between sodium intake and sodium excretion in control rats having access to either 0.5% or 1.5% saline as well as in stressed rats having access to 0.5% saline, this correlation was not observed in stressed rats with 1.5% saline. This suggests that stress impaired the renal capability of rats to handle high sodium but not a slight sodium overload. The inability of the kidney to excrete sodium may be critical to reduce sodium intake after acute immobilization stress.

Chronic immobilization stress reduces sodium intake and renal excretion in rats.

The influence of chronic exposure to immobilization (IMO) on sodium appetite as well as sodium and potassium renal excretion in adult male Wistar rats was studied. The animals were individually housed and all variables under observation were measured in metabolic cages the first, seventh, and thirteenth days once the experiment had started. Half of the rats had access to water, and the remainder of the rats had access to both water and saline solution (1.5% NaCl). IMO reduced the intake of saline solution. Renal water, sodium, and potassium excretion in those IMO rats having access to saline were lower than in control rats. The effects of IMO were very similar during all observation days; therefore no evidence of adaptation to repeated stress was found. The present data indicate the following: (i) IMO stress reduced sodium appetite, probably as a secondary effect to the deficit in sodium renal excretion; (ii) IMO caused antidiuresis and antikaliuresis, only in those rats taking saline solution; (iii) no adaptation to repeated IMO stress was found in any of the tested variables. The reduction of sodium appetite observed in stressed rats might be a homeostatic mechanism to maintain sodium balance after impairment of renal sodium excretion caused by stress.