Invited review: Human, cow, and donkey milk comparison: Focus on metabolic effects.

Milk is an important food of the daily diet. Many countries include it in their dietary recommendations due to its content in several important nutrients that exert beneficial effects on human health. Human milk is a newborn's first food and plays an important role in the growth, development, and future health of every individual. Cow milk is the type of milk most consumed in the world. However, its relatively high content of saturated fats raises concerns about potential adverse effects on human health, although epidemiological studies have disproved this association. Indeed, dairy consumption appear to be linked to a lower risk of mortality and major cardiovascular disease events. In the last few years many researchers have begun to focus their attention on both the production and quality of cow milk as well as the analysis of milk from other animal species to evaluate their effect on human health. The need to investigate the composition and metabolic effects of milk from other animal species arises from the adverse reactions of individuals in several groups to certain components of cow milk. It has emerged that donkey milk compared with that of other animal species, is the nearest to human milk and an excellent substitute for it. Milk from various animal species shows substantial differences in nutritional composition and distinct metabolic effects. In this review, we discussed the main compositional features and metabolic effects of 3 types of milk: human, cow, and donkey milk.

Favourable prognostic role of regression of primary melanoma in AJCC stage I-II patients.

BACKGROUND: The prognostic significance of regression in primary melanoma has been debated over the past few years. Once it was considered to be a negative prognostic factor, as it may have prevented proper melanoma thickness measurement, therefore affecting the staging of the tumours. For this reason, it was considered to be an indication for sentinel lymph node biopsy (SLNB) in melanoma < 1 mm. OBJECTIVES: To ascertain the utility of SLNB in thin melanoma and to clarify the role of regression in disease-free survival (DFS) and overall survival (OS) in our series. METHODS: We analysed data collected from 1693 consecutive patients with AJCC (American Joint Committee on Cancer) stage I-II melanoma. RESULTS: Globally, SLNB was performed in 656 out of 1693 patients. Regression was present in 349 patients and 223 of them were characterized by thin lesions. SLNB was performed in 104 cases of thin melanoma with regression. The majority of regional lymph node metastases were observed in patients who did not undergo SLNB (89 out of 132). Among the remaining 43 'false negative' patients only three showed regression in the primary. Using the Cox multivariate model, histological regression maintained a significant protective role [hazard ratio (HR) 0·62, P = 0·012 for DFS; HR 0·43, P = 0·008 for OS] when corrected for the principal histopathological and clinical features, despite SLNB. CONCLUSIONS: We confirmed that regression alone should not be a reason to perform SLNB in thin melanoma and, on the contrary, it can be considered a favourable prognostic factor in patients with AJCC stage I-II melanoma.

From chronic overfeeding to hepatic injury: role of endoplasmic reticulum stress and inflammation.

We analyse how chronic overfeeding, by increasing circulating fatty acids, might lead to inflammation, insulin resistance (IR) and injury in the liver. Chronic overfeeding causes an increase in adipose tissue depots and is characterised by an increased presence of hypertrophic adipocytes when adipose tissue expandability is inadequate. Adipocyte hypertrophy is a possible stress condition for the endoplasmic reticulum (ER), which will activate inflammatory and apoptotic pathways and cause IR in adipose tissue. Insulin-resistant adipocytes, being more lipolytic and less liposynthetic, induce an increase in circulating free fatty acids. Moreover, the strongly compromised secretion/function of the adipocyte hormones, adiponectin and leptin, decreases lipid oxidation, particularly in the liver, causing lipid accumulation, ER stress and IR in hepatocytes. ER stress may lead to reduced very-low-density lipoprotein (VLDL) secretion and increased lipogenic gene expression despite the presence of IR. These events and reduced lipid oxidation may lead to further hepatic lipid accumulation. When the triglyceride storage capacity of hepatocytes is exceeded, hepatic injury may occur. ER-stressed steatotic hepatocytes activate apoptotic and inflammatory pathways, which trigger IR and the release of chemokines and cytokines, and these, in turn, elicit an increased influx of Kupffer cells (KCs) and hepatic stellate cells (HSCs) around dying hepatocytes. Soluble mediators, secreted mainly by ER-stressed steatotic hepatocytes and activated KCs, induce the transdifferentiation of HSCs to myofibroblasts, which secrete fibrogenic cytokines and matrix components that trigger fibrosis. In conclusion, chronic lipid overloading due to inadequate fat-storing capacity of adipose tissue can induce hepatic injury when triglyceride storage capacity of hepatocytes is exceeded.

From chronic overnutrition to insulin resistance: the role of fat-storing capacity and inflammation.

AIMS: We analyze how the inflammatory state in adipose tissue caused by a condition of chronically positive energy balance can lead to insulin resistance first in adipose tissue, then in all insulin-sensitive tissues. DATA SYNTHESIS: Chronic nutrient overload causes an increase in adipose depots that, if adipose tissue expandability is low, are characterized by an increased presence of hypertrophic adipocytes. This adipocyte hypertrophy is a possible stress condition for the endoplasmic reticulum (ER) that would lead to a proinflammatory state in adipose tissue. In this condition, ER stress would activate metabolic pathways that trigger insulin resistance, release of macrophage chemoattractant proteins, and in chronic inflammation, the death of the hypertrophic adipocyte. The infiltrated macrophages in turn release inflammatory proteins causing further recruitment of macrophages to adipose tissue and the release of inflammatory cytokines. Following these events, insulin resistance becomes extended to all adipose tissue. Insulin-resistant adipocytes, characterized by low liposynthetic capacity and high lipolytic capacity, cause increased release of free fatty acids (FFA). FFA released by lipolitic adipocytes may also activate Toll-like receptors 4 and then chemokines and cytokines release amplifying insulin resistance, lipolysis and inflammation in all adipose tissue. Moreover, increased circulating FFA levels, reduced circulating adiponectin levels and leptin resistance lead to decreased lipid oxidation in non-adipose tissues, thereby triggering ectopic accumulation of lipids, lipotoxicity and insulin resistance. CONCLUSION: All the conditions that increase circulating fatty acids and cause lipid overloading (obesity, lipoatrophy, lipodystrophy, catabolic states, etc.) induce a lipotoxic state in non-adipose tissues that gives rise to insulin resistance.

Does rifaximin prevent complications of diverticular disease? A retrospective study.

While the treatment of complicated diverticular disease (DD) is standardized, the approach to the symptomatic DD and prevention of relapsing complicated DD is still debated. An open question is whether nonabsorbable antibiotics may reduce the incidence of major complications of DD. We wanted to retrospectively analyze the prevalence of this disease in a large population of patients undergoing colonoscopy in our center in the last 10 years. Patients with symptomatic or complicated DD were treated with rifaximin 1,200 mg/die for 10-12 days during the acute phase in addition to the appropriate systemic antibiotics, followed by a prophylactic regimen with 800 mg/die for 7 days every month. The patients were followed up to December 2003, and the incidence of new complications and the relapses of symptomatology were determined. A total of 11,344 patients were screened. Of them, 2,287 showed an anatomical diverticulosis, and 408 had a diagnosis of complicated DD. The results indicate that the prevalence of DD--either in the uncomplicated or complicated form--in our area (Abruzzo, Italy) is identical to that of European countries, whose diet is characterized by a low amount of fiber and a high content of calories and refined sugars. Along a period of 10 years, a relapsing symptomatology of DD was observed in 112 patients treated with rifaximin (4.89%), while new complications of the DD were observed in 27 patients (1.18%). The comparison of these data with those of larger published series suggests a possible role of rifaximin in the prevention of DD main complications.

Dangerous thrombophilic states and internal pathologies: 3 cases of thrombosis of the abdominal veins.

Thrombosis of the abdominal veins is a rare clinical condition which can be assimilated with the more frequent localization of deep venous thrombosis of the lower limbs. In the last few years great attention has been paid to possible risk factors for thrombosis of the abdominal veins. Two risk factors that have been identified are the presence of internal diseases and congenital and/or acquired abnormalities of haemostasis. The authors describe 3 clinical cases (splenic and portal thrombosis due to congenital thrombophilia, Budd-Chiari syndrome, portal cavernoma consequent to ovarian neoplasia) with different etiopathogenesis to show how this apparently rare condition is today more frequently encountered and easier to recognize. In the presence of thrombosis of major venous structures the search and the identification of intrinsic internal risk factors and of congenital and acquired thrombophilic disorders remains of great importance. Screening for thrombophilia includes blood C and S proteins, AT III, homocysteine, Leiden mutation of the factor V gene, G20210A mutation of the prothrombin gene, antiphospholipid antibodies. The presence of one or more of these risk factors allows the identification of the cases of portal thrombosis (EHPVO) responsible for about 10% of all the cases of portal hypertension, without cirrhosis or other hepatic lesions. The primary diagnostic procedure however remains color-Doppler ultrasonography which represents the most simple and the cheapest diagnostic investigation for the study of the portal and suprahepatic vein system, but it's strictly operator dependent.

[Tophaceous gout in plurimetabolic syndrome]. / Gotta tofacea nell'ambito della sindrome plurimetabolica.

Aim of this paper is to describe and discuss, on the basis of the available current literature, the case of a female patient affected by a tophaceous gout associated with plurimetabolic syndrome. Hyperuricemia and gout may be seen today in all the populations of developed countries, with increasing frequency on the last fifty years. Increased production or reduced urinary excretion of uric acid (and hypoxanthine and xanthine) are the most important pathogenetic mechanisms of primary or secondary hyperuricemia. Gout is an acute rheumatic disorder (characterized by a limited range of manifestations) which occurs in humans in connection with deposition of crystals of monosodium urate (the final product of purine metabolism) in the articular and soft periarticular tissues. Hyperuricemia and/or gout are often associated with hyperinsulinemia, obesity, diabetes mellitus, hyperlipemia, hypertension and atherosclerosis to form the syndrome called "Plurimetabolic syndrome" or "Syndrome X". Here we report the clinical case of a 64-year-old female patient who had android obesity, type 2 diabetes mellitus, hypertension, dyslipidemia and hyperuricemia and had been suffering (over many years) from intermittent episodes of severe pain and inflammatory joint swelling (first metacarpo- and metatarso-phalangeal joints) with development of pronounced multiple tophi in bone articular and soft periarticular tissues. Hyperuricemia and acute episodes had never been treated with anti-hyperuricemic drugs because gouty arthritis had never been diagnosed. This severe tophaceous gout associated to multiple metabolic disorders prompted us to present knowledge on gout and to focus on the interrelationships between hyperuricemia and/or gout and plurimetabolic syndrome, important risk factors for coronary heart disease.

Glenohumeral instabilities and the role of MR imaging techniques. The orthopedic surgeon's perspective.

The nature of instability, its diagnostic components, and the facts needed to treat it are presented in this article from the viewpoints of orthopedic surgeons of varying philosophies.

Cardiovascular structural changes and calcium antagonist therapy in patients with hypertension.

Regression of cardiovascular structural changes is a main goal of antihypertensive treatment. Two recent meta-analyses of relatively small noncomparative studies have suggested that angiotensin-converting enzyme (ACE) inhibitors may be more effective than other classes of drugs in inducing regression of left ventricular hypertrophy (LVH). The effect of different antihypertensive drugs on arteriolar structural changes has not yet been properly investigated. The aim of this study was to evaluate the effect of 6 months of treatment with amlodipine (5-10 mg o.d.) or enalapril (10-20 mg o.d.) on blood pressure (BP) (ambulatory monitoring), heart rate (HR), LV mass and function (M-mode echo, two-dimensionally guided), forearm minimal vascular resistance (min VR = BP/max blood flow-venous occlusion plethysmography, taken as an index of vascular structural changes) in 24 hypertensive patients in a comparative single-blind, randomized study, with blind reading of echocardiograms and plethysmographic tracings. After 6 months of treatment with amlodipine 5-10 mg o.d., significant reductions in LV mass index (p = 0.004) and forearm min VR (p = 0.02) were observed. Before and during treatment, LV systolic function, both at rest and during stress (handgrip test), evaluated by fractional shortening as related to end-systolic stress, was in every case within 95% confidence limits calculated in normal subjects. Similar results were observed with enalapril. No significant differences were observed for Doppler indices of diastolic filling after 6 months of treatment with either drug. These results indicate that a significant regression of structural changes in the heart and in the small resistance vessels can be observed after long-term treatment with amlodipine in essential hypertensive patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Glenohumeral instabilities and the role of magnetic resonance imaging techniques. The orthopedic surgeon's perspective.

Orthopedic surgeons often have different philosophies regarding the diagnosis and treatment of glenohumeral instability. Some surgeons will rely extensively on imaging studies to ascertain pathology relevant to a specific method of treatment; others will only use imaging in cases where the diagnosis is uncertain. This article reviews the concept of glenohumeral instability and its treatment.

Unusual case of anuria due to African bee stings.

We describe a case of multiple African bee stings in which the exceptionally high dose suggests a direct effect of hymenoptera venom on the renal tubules. The case does not follow the previously reported pattern of hypovolemic or anaphylactic shock, hemolysis and/or rhabdomyolysis, despite the potentially lethal amount of venom injected.

The role of angiography in penetrating neck trauma.

Seventy-two consecutive patients who underwent neck arteriography were reviewed to assess recent suggestions that angiography is not indicated in asymptomatic patients with penetrating neck trauma. Proximity to major neck vessels without signs or symptoms of vascular trauma was the reason for angiography in ten of 26 patients with proven arterial injuries. Physical examination had a specificity of 80% and a sensitivity of 61% in this series. There was no correlation between mechanism or location of penetration and the likelihood of clinically significant injury. We conclude that recent recommendations suggesting that arteriography is unnecessary in asymptomatic patients with penetrating neck trauma are premature. Further investigations of larger patient samples are necessary to determine if "proximity" should be abandoned as an indication for arteriography. We advocate that, until additional data are accumulated, urgent arteriography and esophagography or operative exploration are indicated in stable asymptomatic patients with neck wounds which violate the platysma.

Flow cytometric analysis of leukocytes eluted from haemodialysers.

The cellular immune system is impaired in uraemic and haemodialysed patients. We describe a method of studying leukocytes eluted from dialysers at the end of the dialysis session, and we have studied five haemodialysers: cuprophane (CU), cellulose acetate (CA), polymethylemethacrylate (PMMA), polyacrylonitrile (PN), and polysulphone (PS). The analysis was performed by flow cytofluorimetry using monoclonal antibodies. The absolute number of eluted leukocytes was rather elevated, ranging from 88 (CU) to 9 (PS) millions of cells. When compared to peripheral blood values, the percentage analysis revealed an increase of PMN and monocytes and a decrease of lymphocytes. A relative increase of B lymphocytes was observed in all filters studied. A trapping of T lymphocytes (PAN) and a minor increase of NK cells (PMMA, PS, CA) were also observed. The elution of leukocytes from dialysers may be helpful in evaluating the biocompatibility of membranes for haemodialysis.

Tubular nephrotoxicity after intravenous urography with ionic high-osmolal and nonionic low-osmolal contrast media in patients with chronic renal insufficiency.

Nephrotoxicity of intravenous contrast media is more frequent and striking in patients with risk factors, the major one being preexisting chronic renal insufficiency. New nonionic low-osmolal contrast media allegedly have less nephrotoxicity than the traditional ionic high-osmolal ones. This was tested for two contrast media in a group of 18 patients with stable chronic renal insufficiency. The urinary excretion of two brush-border enzymes (alanine aminopeptidase, AAP, and gamma-glutamyl transpeptidase, gamma-GT) and of a lysosomal enzyme (N-acetyl-beta glucosaminidase, NAG), functional markers of tubular injury, were measured before and after intravenous urography with an ionic high-osmolal radiocontrast medium, meglumine sodium diatrizoate, or with a non ionic low-osmolal one, iopamidol. Urinary NAG excretion did not change significantly after administration of either contrast media. Urinary AAP and gamma-GT excretion increased significantly (p less than 0.01) after diatrizoate. After iopamidol, only gamma-GT excretion increased significantly (p less than 0.05). Our data suggest that the nonionic low-osmolal radiocontrast medium iopamidol is less toxic to tubules than the ionic high-osmolal medium diatrizoate and that the brush-border enzymes AAP and gamma-GT are sensitive markers for this toxicity.