Butyrate as an effective treatment of congenital chloride diarrhea

BACKGROUND & AIMS: Many therapeutic attempts have demonstrated to be ineffective in reducing the severity of congenital chloride diarrhea and its long-term complications. The short-chain fatty acid butyrate stimulates intestinal water and ion absorption through a variety of mechanisms, including the activation of a parallel Cl-/butyrate and Na+/H+ exchanger. In this case report, we report the therapeutic efficacy of butyrate on an 11-year-old patient affected by congenital chloride diarrhea. METHODS: The efficacy of increasing doses of oral butyrate (from 50 to 100 mg/kg/day) was investigated through the daily evaluation of stool volume, bowel movements, fecal incontinence, serum, and stool electrolytes concentrations. The modifications in transepithelial intestinal ion transport elicited by butyrate were examined by rectal dialysis study. RESULTS: A butyrate dose of 100 mg/kg/day induced a normalization of stool pattern and of serum and fecal electrolytes concentration. The rectal dialysis study demonstrated a proabsorptive effect induced by butyrate on Na+, Cl-, and K+ intestinal transport. Butyrate therapy was well tolerated during the entire 12-month observation period, and the stool pattern and fecal and serum ion concentrations remained stable within the normal ranges. No clinical adverse events or episodes of dehydration requiring hospital care were observed. CONCLUSIONS: Butyrate could be effective in treating congenital chloride diarrhea. It is easily administered, useful in preventing severe dehydration episodes, and may be a promising therapeutic approach for a long-term treatment in this rare and severe condition.     

Stem cells in the dog heart are self-renewing, clonogenic, and multipotent and regenerate infarcted myocardium, improving cardiac function

The purpose of this study was to determine whether the heart in large mammals contains cardiac progenitor cells that regulate organ homeostasis and regenerate dead myocardium after infarction. We report that the dog heart possesses a cardiac stem cell pool characterized by undifferentiated cells that are self-renewing, clonogenic, and multipotent. These clonogenic cells and early committed progeny possess a hepatocyte growth factor (HGF)-c-Met and an insulin-like growth factor 1 (IGF-1)-IGF-1 receptor system that can be activated to induce their migration, proliferation, and survival. Therefore, myocardial infarction was induced in chronically instrumented dogs implanted with sonomicrometric crystals in the region of the left ventricular wall supplied by the occluded left anterior descending coronary artery. After infarction, HGF and IGF-1 were injected intramyocardially to stimulate resident cardiac progenitor cells. This intervention led to the formation of myocytes and coronary vessels within the infarct. Newly generated myocytes expressed nuclear and cytoplasmic proteins specific of cardiomyocytes: MEF2C was detected in the nucleus, whereas alpha-sarcomeric actin, cardiac myosin heavy chain, troponin I, and alpha-actinin were identified in the cytoplasm. Connexin 43 and N-cadherin were also present. Myocardial reconstitution resulted in a marked recovery of contractile performance of the infarcted heart. In conclusion, the activation of resident primitive cells in the damaged dog heart can promote a significant restoration of dead tissue, which is paralleled by a progressive improvement in cardiac function. These results suggest that strategies capable of activating the growth reserve of the myocardium may be important in cardiac repair after ischemic injury.     

Regression of left ventricular hypertrophy and systolic function in hypertensive patients during long-term treatment with ketanserin

Summary It is now generally accepted that antihypertensive therapy can induce regression of left ventricular hypertrophy (LVH) in hypertensive subjects. However, the influence of LVH reversal on both the systolic and diastolic functions, and particularly the ability of the heart to meet sudden overloads caused by exercise and/or recurrence of hypertension, remain unanswered questions. The long-term effects of ketanserin, a selective serotonin S₂-receptor antagonist with additional alpha₁-adrenergic blocking properties, on LVH and systolic function were studied in 13 untreated subjects (age range 35–55 years) with mild-to-moderate essential hypertension, echocardiographic evidence of LVH, and normal ejection fraction. Blood pressure values and echocardiographic measurements of dimensions, wall thicknesses, and indices of LV mass were determined before and after 3, 6, and 12 months treatment; ejection fractions at rest and during exercise were evaluated by equilibrium multigated radionucleide angiocardiography at baseline and after 12 months of therapy. Mean arterial pressure was significantly reduced from the first month of treatment (p<0.001) and remained well controlled up to the end of the trial. Both posterior and septum wall thicknesses decreased after 3 months of therapy and remained stable throughout the whole study period. LV mass index decreased from a mean ± SD of 187.7±47.6 g/m² to a mean of 157.81±31.63 g/m² (p<0.01) at the third month, reaching greater decreases after 6 months (156.05±31.00 g/m²) and after 12 months (153.21±28.80 g/m²) of treatment. A significant correlation was found between LV mass and posterior wall thickness at the different observation times in the study. Finally, the regression of LVH at the end of therapy was not associated with impairment of systolic function, as assessed by measurements of ejection fraction at rest and during exercise.     

Biological and clinical features of acute lymphoblastic leukaemia with cytoplasmic granules or inclusions: description of eight cases

We describe eight patients (four children and four adults) with an acute lymphoblastic leukaemia (ALL) with cytoplasmic granules or inclusions. The incidence of this variant of acute leukaemia in our whole series of patients with ALL is 1.8%. The granules or inclusions were usually positive for aspecific esterases (ANAE) and/or acid phosphatase, and the immunophenotype was in all cases typical of a CALLA positive B-lineage ALL (CD10+, CD19+ and/or CD24+, DR+, TdT+, anti-T-, anti-My-, SIg-). In one paediatric case, CD33 was unusually coexpressed. Ultrastructural investigations were performed in one case and demonstrated large granules containing vesicles, usually membrane bound, in the majority of blast cells. In the two cases analysed, Ig heavy chain gene rearrangement was detected. In this series of patients prognosis was poor since three never achieved a complete remission, four relapsed and only one is still in first continuous remission.     

Clinical spectrum of fungal infections after orthotopic liver transplantation

During a 50-month period, we identified 91 episodes of fungal infection in 72 liver transplant recipients (23.8%). Candida species accounted for 83.5% of cases. Clinical patterns of fungal infections included disseminated infection (19), peritonitis (17), pneumonitis (15), multiple sites of colonization (13), fungemia (11), and other sites (16). The diagnosis of fungal infection was usually made in the first 2 months (84.7% of cases), at a mean time of 16 days after transplantation. Risk factors for fungal infections included retransplantation, Risk score, intraoperative transfusion requirement, urgent status, Roux limb biliary reconstruction (in adults), steroid dose, bacterial infections and antibiotic therapy, and vascular complications. Fungal infections were successfully treated with amphotericin B in 63 cases (74.1%) but were associated with diminished patient survival (50% vs 83.5%). Fungal infection is a frequent source of early morbidity and can be related to well-defined risk factors, suggesting the need for effective prophylaxis.     

Antioxidant Properties of Lunularia Cruciata (Bryophyta) Extract

The effects of Lunularia cruciata (L.) Dum (Bryophyta) acetonic extract was studied in vitro by means of luminol-dependent chemiluminescence (CL) emission from human peripheral whole blood phagocytes and isolated polymorphonuclear leukocytes (PMNs). L. crudata adult thalli underwent extraction with acetone. CL emission was evaluated in an automated luminometer, measuring the oxygen free-radical production by phagocytes incubated with opsonized zymosan (OZ) or phorbol myristate acetate (PMA), in absence or in presence of various concentrations of L. crudata extract. The CL results indicated that L. crudata induced significant changes in light emission from whole blood phagocytes, as well as isolated PMNs. Its inhibitory activity was more evident when resting isolated PMNs were studied. When the cells were activated, the greatest inhibitory effect was observed with PMA. The L, crudata activity could be caused by several compounds, such as flavonoids and or sesquiterpenes, present in the acetonic extract.     

Computerized M-mode echocardiography in the assessment of cardiovascular effects during intravenous administration of amiodarone

Antianginal and antiarrhythmic long term therapy with amiodarone may be associated with side effects, therefore it should be used mainly in short term treatment of severe arrhythmias and acute coronary insufficiency. It is important to assess if any inotropic effect may be produced after intravenous administration of this drug in commonly accepted therapeutic doses (5 mg/kg body weight). To investigate this possibility we studied the effects of amiodarone on blood pressure (BP), on heart rate (HR) and on the maximal velocity of circumferential fiber shortening (Vcf Max). Simultaneous echocardiogram (UCG), electrocardiogram (lead DII) (ECG) and BP cuff measurement were performed on 12 subjects without cardiomegaly and clinical evidence of heart failure, immediately before a 30 second intravenous injection of amiodarone and every 30 seconds over a period of 6 minutes after drug administration. Amiodarone administration markedly raised HR within the first 30 seconds from the beginning of the injection and concomitantly decreased diastolic BP. No significant lowering of systolic BP was observed. Vcf Max (circ/sec) raised during the test concomitantly with HR increase, showing a significant relationship between left ventricular performance and HR. The same was also true during atrial pacing performed on one subject. No significant changes in any of the parameters studied were demonstrated after placebo (saline solution) administration to two presumable healthy subjects. Amiodarone does not seem to have any positive or negative intrinsic inotropic effect when administered intravenously at a dose of 5 mg/kg body weight.