Efficacy of Bifidobacterium breve CECT7263 for infantile colic treatment: an open-label, parallel, randomised, controlled trial.

Infantile colic is a prevalent condition characterised by excessive crying with no effective treatment available. We aimed to evaluate the efficacy of Bifidobacterium breve CECT7263 and a combination of this and Lactobacillus fermentum CECT5716 versus simethicone in reducing the daily time spent crying in colicky infants. A multicentre randomised, open-label, parallel, controlled trial of 28 days was performed in 150 infants who were diagnosed with colic according to the Rome III criteria and who randomly received simethicone (80 mg/day; Simethicone group), B. breve CECT7263 (2×108 cfu/day, Bb group), or a combination of L. fermentum CECT5716 and B. breve CECT7263 (1×108 cfu/day per strain, Bb+Lf group). The main outcomes were minutes of crying per day and the percentage of reduction in daily crying from baseline. Data were analysed per intention to treat. All treatments significantly decreased the daily crying time at the end of the intervention (P-time <0.001). However, the infants in the Bb group had significantly decreased crying time from the first week of the study (P<0.05), whereas the Bb+Lf group and the simethicone group had significantly decreased crying time from the second week (P<0.05). The percentage of reduction in the minutes of crying from baseline in the Bb group was significantly higher than that in the Simethicone group every week of the intervention (-40.3 vs -27.6% at 1-week; -59.2 vs -43.2% at 2-weeks; -64.5 vs -53.5% at 3-week and -68.5 vs -59.5% at 4-weeks, P<0.05). Additionally, in the Bb group, infants had better night sleep, and parents reported a more positive mood at the end of the intervention. All the products used in the study were safe and well tolerated. In conclusion, the breastmilk-isolated probiotic strain B. breve CECT7263 is a safe and effective treatment for infantile colic, presenting an earlier and more robust effect than the reference prescribed drug, simethicone.

Effects of Lactobacillus fermentum CECT5716 Lc40 on infant growth and health: a randomised clinical trial in nursing women.

The breast milk microbiota has been described as a source of bacteria for infant gut colonisation. We studied the effect of Lactobacillus fermentum CECT5716 (Lc40) on growth and infection incidence of the infants, when the probiotic is administrated to the mothers. Moreover, whether such effects might depend on the interaction between the mother or infant microbiota and the probiotic administration. A total of 291 mother-infant pairs were studied for 16 weeks in a randomised double-blinded placebo-controlled multicentre trial. The Lc40 group (n=139) received 1 capsule/day containing 3×109 cfu Lc40; the control group (n=152) received 1 placebo (maltodextrin) capsule/day. A positive and significant correlation of the Staphylococcus load between breast milk and infant faeces was only observed in control group. Additionally, the weight z-score of the infants whose mothers had higher values of Lactobacillus in their breast milk were significantly higher for the Lc40 group. We observed a significant lower incidence of conjunctivitis in the infants whose mothers received Lc40. A higher load of Staphylococcus in infant faeces significantly increased the risk of respiratory infections. Such incidence, under an absent or low Staphylococcus load in the faeces, was significantly 36 times higher in the infants in the control group than in the infants in the Lc40 group. However, the protective effect of Lc40 was gradually reduced as the Staphylococcus load of the milk increased. The administration of Lc40 to nursing women might influence infant growth and health but it seems to depend on its interactions with mother or infant microbiota. Registered in the US Library of Medicine (www.clinicaltrials.gov): NCT02203877.

Evaluation of the safety, tolerance and efficacy of 1-year consumption of infant formula supplemented with Lactobacillus fermentum CECT5716 Lc40 or Bifidobacterium breve CECT7263: a randomized controlled trial.

BACKGROUND: The microorganism present in breast milk, added to other factors, determine the colonization of infants. The objective of the present study is to evaluate the safety, tolerance and effects of the consumption of a milk formula during the first year of life that is supplemented with L. fermentum CECT5716 or Bifidobacterium breve CECT7263, two strains originally isolated from breast milk. METHODS: A randomized, double blind, controlled, parallel group study including healthy, formula-fed infants was conducted. Two hundred and thirty-six 1-month-old infants were selected and randomly divided into three study groups according to a randomization list. Infants in the control group received a standard powdered infant formula until 12 months of age. Infants in the probiotic groups received the same infant formula but supplemented with L. fermentum CECT5716 Lc40 or B. breve CECT7263. Main outcome was weigh-gain of infants as safety marker. RESULTS: One hundred and eighty-nine infants completed the eleven months of intervention (61 in control group, 65 in Lf group and 63 in Bb group). The growth of infants in the three groups was consistent with standards. No significant differences were observed in the main outcome, weight-gain (Control group: 5.77 Kg ± 0.95, Lf group: 5.77 Kg ± 1.31, Bb group: 5.58 Kg ± 1.10; p = 0.527). The three milk formulae were well tolerated, and no adverse effects were related to the consumption of any of the formula. Infants receiving B. breve CECT7263 had a 1.7 times lower risk of crying than the control group (OR = 0.569, CI 95% 0.568-0.571; p = 0.001). On the other hand, the incidence of diarrhoea in infants receiving the formula supplemented with L. fermentum CECT5716 was a 44% lower than in infants receiving the control formula (p = 0.014). The consumption of this Lactobacillus strain also reduced the duration of diarrhoea by 2.5 days versus control group (p = 0.044). CONCLUSIONS: The addition of L. fermentum CECT5716 Lc40 or B. breve CECT7263, two probiotic strains naturally found in breast milk, to infant formulae is safe and induces beneficial effects on the health of infants. TRIAL REGISTRATION: The trial was retrospectively registered in the US Library of Medicine ( www.clinicaltrial.gov ) with the number NCT03204630 . Registered 11 August 2016.

Long-term safety of early consumption of Lactobacillus fermentum CECT5716: A 3-year follow-up of a randomized controlled trial.

Lactobacillus fermentum CECT5716 is a probiotic strain originally isolated from human breast milk. Previous clinical studies in infants showed that the early administration of a milk formula containing this probiotic strain was safe and may be useful for the prevention of community-acquired infections. This is a 3-year follow-up study aimed at evaluating the long-term effects produced by the early consumption of an infant formula supplemented with L. fermentum CECT5716 (experimental group, EG) compared with a control formula without the probiotic (control group, CG). The infants included in this follow-up study had previously completed a 5-month randomized double-blind controlled trial (from 1 to 6 months of age), where the safety and tolerance of the probiotic formula was evaluated. The main outcome of the follow-up study was the growth of the children. The secondary outcomes included the incidence of infectious and non-infectious diseases, parameters related with intestinal function and faecal microbiota. At 3 years, the mean values of weight, length and head circumference were similar in children of the EG compared with those of the CG. No differences were observed in the incidence of infectious and non-infectious diseases or disorders related with intestinal function. The pattern of faecal microbiota was also similar between both groups. In conclusion, this 3-year study shows that the early administration of the probiotic of L. fermentum CECT5716 in an infant formula is safe and it does not produce measurable differences in children compared with a control formula.

Increased plasma pancreastatin-like levels in gestational diabetes: correlation with catecholamine levels.

OBJECTIVE: To investigate plasma pancreastatin (a chromogranin A-derived peptide) and catecholamine levels (counterregulatory hormones) in subjects with gestational diabetes compared with normal pregnant subjects. RESEARCH DESIGN AND METHODS: Fasting blood samples were obtained from 11 normal pregnant and 12 nonobese gestational diabetic subjects at late pregnancy (30+/-1 weeks). Selection criteria were those recommended by the National Diabetes Data Group (modified from O'Sullivan original criteria). Plasma glucose, insulin, glucagon, pancreastatin-like, epinephrine, and norepinephrine were measured. RESULTS: Gestational diabetic subjects had significantly higher insulin levels than control pregnant subjects (18+/-1 vs. 15+/-1 microU/ml), whereas glucose and glucagon levels where comparable in the two groups. However, increased catecholamine levels (epinephrine and norepinephrine) were found in the gestational diabetic group. We also found increased pancreastatin-like levels in these patients compared with the pregnant control group (46+/-2 vs. 30+/-2 pmol/l). Actually, pancreastatin levels positively correlated with both epinephrine (r = 0.34) and norepinephrine (r = 0.80) levels. CONCLUSIONS: Catecholamine and pancreastatin-like levels were found elevated in gestational diabetic subjects. These counterregulatory hormones may play a role in the insulin resistance syndrome of gestational diabetes.

Thyroid peroxidase autoantibodies predict poor metabolic control and need for thyroid treatment in pregnant IDDM women.

OBJECTIVE: To study whether the presence of antithyroid peroxidase antibodies (TPO-Abs) before gestation in IDDM affects thyroid function and metabolic control during pregnancy and early postpartum as well as neonatal outcome. RESEARCH DESIGN AND METHODS: A prospective study at an outpatient endocrine-obstetric unit was carried out in 20 pregnant IDDM women. Free T4 (thyroxine), thyroid-stimulating hormone (TSH), TPO-Abs, and HbA1c were assayed before gestation; during the first, second, and third trimester of pregnancy; and 3 months postpartum. RESULTS: HbA1c was significantly higher in TPO-Ab+ women than in those who were TPO-Ab- during the second (P < 0.01) and third (P < 0.05) trimesters. HbA1c levels significantly decreased in TPO-Ab- patients when the second (P < 0.01) and third (P < 0.05) trimesters were compared with before the pregnancy and the first trimester. There was a significant increase in the dosage of insulin for TPO-Ab+ versus TPO-Ab- patients during the second (P < 0.05) and third (P < 0.01) trimesters and 3 months postpartum (P < 0.05). TSH was significantly increased in the second (P < 0.001) and third (P < 0.05) trimesters and 3 months postpartum (P < 0.01) when compared with TPO-Ab- patients; 7.6% of the TPO-Ab- group and 29% in the TPO-Ab+ group presented postpartum thyroid dysfunction, and 42% of the TPO-Ab+ women required thyroid treatment. CONCLUSIONS: Pregnant women with IDDM who have a positive test for TPO-Abs before gestation have poorer glucose control and a high prevalence of hypothyroidism. Therefore we recommend that prepregnant IDDM patients be screened for anti-TPO-Abs. Those with a positive result should be followed with serial monitoring of free T4 and TSH levels during each trimester as well as the postpartum period.

Plasma pancreastatin-like immunoreactivity correlates with plasma norepinephrine levels in essential hypertension.

Pancreastatin (PST), a 49 amino acid peptide originally isolated from porcine pancreas, is derived from chromogranin A (Cg A), an acidic protein co-released with catecholamines from sympathetic nerve terminals and chromaffin cells. Extracellular processing of Cg A yields PST as well as other biological active peptides. Measurement of Cg A and PST-like immunoreactivity (PST-LI) has been used to investigate patients with pheochromocytoma and other neuroendocrine neoplasia. Some studies have found increased plasma norepinephrine (NE) levels in essential hypertension. We therefore measured venous plasma PST-LI and catecholamines in patients with essential hypertension. We employed a radioimmunoassay developed with commercially available reagents for measuring plasma PST-like immunoreactivity, and HPLC with electrochemical detection for measurement of plasma catecholamines. The correlation of PST-LI with epinephrine (E) was very weak. However, its correlation with NE was highly significant. Thus, venous plasma PST-LI immunoreactivity may reflect sympathetic nerve activity in essential hypertension.

Increased plasma pancreastatin-like immunoreactivity levels in non-obese patients with essential hypertension.

DESIGN: Pancreastatin, a novel peptide, is known to inhibit insulin secretion and to have a glycogenolytic effect, and is present in many endocrine and chromaffin cells. Both the plasma insulin levels and the adrenergic activity accompanying insulin resistance have been shown to be increased in hypertensive subjects. Our working hypothesis was that pancreastatin might play a role in these pathological phenomena. METHODS: We studied the plasma pancreastatin level in non-obese essential hypertensive patients in response to an intravenous glucose load. We further measured the responses to the glucose challenge of insulin, glucagon, catecholamines and free fatty acids, as well as other factors related to insulin resistance (i.e. lipoproteins and apolipoproteins). We separated the hypertensive patients into three groups according to their response to an oral glucose-tolerance test: normoinsulinaemic, hyperinsulinaemic and glucose-intolerant. Matched normotensive control subjects were also studied. RESULTS: Pancreastatin levels did not change in the control group after the glucose challenge. However, all hypertensive patients showed an increase in plasma pancreastatin levels after glucose loading. The normoinsulinaemic hypertensive patients also had elevated basal pancreastatin levels. The increase in pancreastatin levels was in the ranking: normoinsulinaemic > hyperinsulinaemic > glucose-intolerant. The pancreastatin: insulin ratio showed that the secretion of pancreastatin and insulin may be regulated differently. Basal free fatty acid and glucagon levels were found to be elevated both in the hyperinsulinaemic and in the glucose-intolerant group. Fasting triglycerides levels were increased in all of the hypertensive patients. Other risk factors for coronary artery disease were also found to be altered: elevated very low-density lipoprotein-cholesterol and decreased high-density lipoprotein-cholesterol, with ranking: normoinsulinaemic < hyperinsulinaemic < glucose-intolerant. CONCLUSIONS: These results show an increase in pancreastatin levels in hypertensive patients, suggesting that pancreastatin might play a role in the pathophysiology of essential hypertension.

Diminished insulin receptors on erythrocyte ghosts in nonobese patients with essential hypertension independent of hyperinsulinemia.

Hypertension is associated with insulin resistance and dyslipidemia in a syndrome named X. Epidemiologic evidence also supports a link between hyperinsulinemia and blood pressure (BP), independent of obesity and non-insulin-dependent diabetes mellitus. To assess the possible role of insulin receptors in this syndrome, we studied insulin binding by erythrocyte ghosts in patients with moderate essential hypertension with or without fasting or postglucose hyperinsulinemia. We measured plasma glucose and insulin before and at 30, 60, and 120 min after administration of 75 g glucose in 62 hypertensive patients and 20 matched normotensive controls. Both groups had comparable age (mean 45 years) and waist/hip ratios (mean 0.88). Patients undergoing antihypertensive treatment did not receive antihypertensive medication for 3 weeks. Patients with fasting or postglucose hyperglycemia were excluded from the study. Insulin binding to erythrocyte ghosts was significantly decreased (p < 0.001) to almost half the values of controls (6.5% specific binding) in both patients with hyperinsulinemic (3.2% specific binding) and those with normoinsulinemic (3.9% specific binding) hypertension. Scatchard analysis demonstrated that this was due to a lesser number of insulin receptors. These data indicate that patients with essential hypertension can show decreased erythrocyte insulin receptors without detectable hyperinsulinemia.

[Familial hypobetalipoproteinemia: description of a heterozygous form with important biochemical alterations]. / Hipobetalipoproteinemia familiar: descripción de una forma heterocigota con importantes alteraciones bioquímicas.

We describe a case of a patient affected of familial hypobetalipoproteinemia with marked biochemical alterations (low cholesterol and triglyceride levels) which are characteristic of the homocygote form and with no apparent clinical manifestations. The determination of Apoprotein B and the family study permitted the diagnosis of a heterocygote form.

Effect of captopril at two different dosage regimens in hypertensive non-insulin dependent patients.

Thirty patients (21 F, 9 M) of mean age 55.3 years with non-insulin dependent diabetes mellitus of mean duration 10.8 years and hypertension (blood pressure 160/95 mm Hg) of 0.3 to 4.0 years were randomly allocated to either a twice daily regimen of captopril (50 mg twice daily, Group A) or a once daily captopril schedule (50 mg once daily, Group B). Good glycaemic control (HbA1c, mean 7.63%) had been achieved with sulphonylureas in 22 patients and insulin in 8 patients. There were no statistical differences in baseline values between the two groups. For the 15 patients in Group A, blood pressure fell significantly from a baseline of 177 +/- 13.2/106 +/- 7.8 mm Hg to 161 +/- 14.3/91 +/- 6.9 after one month (P less than 0.05) and continued to decrease at 3 and 6 months. In Group B the blood pressure changed from 179 +/- 19.0/110 +/- 15.6 to 169 +/- 21.0/98 +/- 7.2 at 1 month (P less than 0.05) with further reductions again seen at 3 and 6 months. Nine patients had poorer response than the other 21 but there were no demographic differences between these subgroups nor were there any differences in plasma renin activity or aldosterone responses. There were no statistically significant changes in haematological or biochemical values in either group during treatment. In particular, HbA1c and fasting glucose were unaffected by captopril treatment. No side effects were encountered during the 6 months of follow-up. In conclusion, captopril is an effective antihypertensive in non-insulin dependent diabetes mellitus with mild to moderate hypertension and a once daily regimen could improve compliance.