Herbal supplements in pregnancy: unexpected results from a multicentre study.

STUDY QUESTION: How common is the use of herbal supplements during pregnancy and does it adversely affect the pregnancy outcome? SUMMARY ANSWER: The use of herbal products during pregnancy is very common and daily almond oil spreading is associated with preterm birth (PTB). WHAT IS KNOWN AND WHAT THIS PAPER ADDS: Herbal drugs are often promoted as 'natural' and 'safe' and such claims attract pregnant women. More than a quarter of Italian pregnant women consume herbs every day for at least 3 months during pregnancy. We raise an alert over the habit of daily almond oil spreading since it seems to be associated with PTB. DESIGN: A multicenter retrospective cohort study performed over a 15-month period. PARTICIPANTS AND SETTING: Seven hundred women interviewed within 3 days of childbirth, in three public hospitals in northern Italy. MAIN RESULTS AND ROLE OF CHANCE: One hundred and eighty-nine women were considered 'regular users', since they consumed herbs every day, for at least 3 months. Almond oil, chamomile and fennel were the most commonly used herbs. Both length of gestation and birthweight were affected by herb consumption. Almond oil users showed more pre-term birth (29 of 189) than non-users (51 of 511). After adjusting for multiple pregnancies, smoking, advanced age and drug intake, almond oil users maintained an increased risk to give birth <37th week (odds ratio = 2.09, 95% confidence interval: 1.08-4.08). BIAS, CONFOUNDING AND OTHER REASONS FOR CAUTION: The association between daily spreading of almond oil and PTB only raises a hypothesis that requires confirmation in larger trials devoted to this topic. The relatively small sample size did not allow the investigation of other adverse pregnancy outcomes in herb users. GENERALIZABILITY TO OTHER POPULATIONS: The population under investigation did not significantly differ from the general population attending the same hospitals. STUDY FUNDING/COMPETING INTEREST(S): No conflict of interest exists. The study has been supported by a public grant from the University of Modena and Reggio Emilia. TRIAL REGISTRATION NUMBER: None.

Potential risk factors for the development of acute renal failure in preterm newborn infants: a case-control study.

AIMS: To determine in a case-control study possible associations between the development of acute renal failure in preterm newborns and therapeutic interventions, particularly drug treatments. METHODS: The study population was 172 preterm infants of <38 weeks gestation; 71 had acute renal failure and 101 were controls closely matched for gestational age and birth weight. Maternal and neonatal information was collected for both groups through questionnaires and interviews. Routine data on renal variables were also collected. Univariate and multivariate logistic regression analyses were performed. RESULTS: Very low birthweight infants were at high risk of acute renal failure (79% of cases were <1500 g). However, the acute renal failure was transient. Mothers of infants with acute renal failure received more drugs during pregnancy and delivery (mainly antibiotics and non-steroidal anti-inflammatory drugs). Of the possible therapeutic interventions, intubation, catheterisation, and phototherapy were mainly applied to case subjects. A low Apgar score and patent ductus arteriosus were diagnosed in a greater percentage of neonates with acute renal failure. Moreover, in the first few days of life and before diagnosis of acute renal failure, case subjects received more drugs (antibiotics, non-steroidal anti-inflammatory drugs, and diuretics) and for a longer time. In the multivariate logistic analysis, medullary hyperechogenicity (odds ratio (OR) 4.491; 95% confidence interval (CI) 1.879 to 10.731) and ceftazidime administration (OR 5.082; 95% CI 1.493 to 17.297) were associated with a greater risk of acute renal failure. CONCLUSIONS: The results suggest the need for careful monitoring of very low birthweight infants and attention to drug treatments, as it is difficult to differentiate between normality and renal failure in the first few days of life.

NSAID-induced nephrotoxicity from the fetus to the child.

In this review we report data available from the literature on the use of nonsteroidal anti-inflammatory drugs (NSAIDs) and the development of nephrotoxicity in the fetus, neonates and children. Up to the present day, several cases of severe and sometimes irreversible renal insufficiency have been described in neonates exposed to indomethacin prenatally or in the first days of life for treatment of patent ductus arteriosus (PDA). Until now, very few studies have been carried out on alternative treatments for PDA in preterm infants; ibuprofen has been shown to be as effective as indomethacin in closing the ductus in this patient group without affecting renal function. In children, NSAID-induced renal failure is a rare event and is usually reversible after discontinuation of the drug. However, caution should be taken when NSAIDs are administered to individuals with preexisting renal problems or with other potentially nephrotoxic drugs. In these situations, new approaches such as cyclo-oxygenase-2 selective inhibitors or prostanoid receptor selective antagonists could lead to alternative therapies for use in paediatrics.

Nutritional supplementation with copper in the rat. I. Effects on adjuvant arthritis development and on some in vivo- and ex vivo-markers of blood neutrophils.

OBJECTIVE AND DESIGN: The aims of the work were: 1) to confirm the preliminarily observed anti-arthritic potential of a 200 ppm copper-supplemented diet in the rat: 2) to study the impact of the nutritional treatment and of the experimental pathology on neutrophil activity. ANIMALS AND CELLS: Two hundred female Sprague-Dawley rats were used. Polymorphonuclear leukocytes were isolated from these animals for the ex vivo studies. TREATMENT: Control-rats were maintained on a standard diet containing 5 ppm of copper. Supplemented-rats were kept on a diet containing 200 ppm of the metal. METHODS: Mycobacterium butyricum-induced arthritis was studied. Flame atomic absorption spectroscopy was used to assess copper and zinc levels. The "microplate-assay" technique was used to determine serum lysozyme concentration (lysis of Micrococcus lysodeikticus cell walls), as well as neutrophil O2- generation (superoxide dismutase-inhibitable reduction of ferricytochrome-c), and adhesion (activity of the membrane enzyme acid phosphatase). The results were statistically evaluated by the Student's t test. RESULTS: The nutritional copper-supplementation: 1) significantly inhibited the adjuvant-arthritis development (33% +/- 5, P<0.01); 2) did not modify lysozyme secretion or superoxide production; 3) significantly decreased the percentage of cell adhesion by an average of 41% +/- 19 (P<0.01). CONCLUSIONS: The copper-supplemented diet has an anti-arthritic effect which may be also primed by the effect of copper on the expression of the neutrophil cell-adhesion molecules.

Effects on intestinal microflora, gastrointestinal tolerability and antiinflammatory efficacy of diclofenac and nitrofenac in adjuvant arthritic rats.

Since it is known that nitric oxide plays an important protective role in maintaining the tissue integrity and is cytotoxic for invasive micro-organisms, diclofenac and a new original diclofenac-derivate, nitrofenac (containing the nitric oxide group), was administered at doses of 0.3 and 3 mg kg-1 per os to adjuvant arthritic rats. At the 14th, 21st and 28th days after arthritis induction, the antiinflammatory efficacy and the effects on intestinal microflora of the two drugs were evaluated; moreover, at the end of the study period, the gastrointestinal tract was examined macroscopically for any presence of lesions. Daily oral administration of diclofenac and nitrofenac at 3 mg kg-1 markedly and significantly inhibited arthritis development until the end of the study period. Some significant changes were observed in anaerobic and Gram-negative bacterial flora, particularly the total disappearance, in all treated rats, of Escherichia coli 1, also 7 days after the last drug administration. Finally, no ulcers or severe damage were observed macroscopically with either drug, even if some alterations in the mucosa and haemorrhagic effusions were more evident in rats treated with diclofenac at 3 mg kg-1. In conclusion, in this chronic model a similar therapeutic efficacy of diclofenac and nitrofenac is shown in arthritic rats. The better gastrointestinal tolerability observed in nitrofenac-treated rats could be attributed to the release of nitric oxide.

Gastrointestinal effects of single and repeated doses of ferrous sulphate in rats.

The gastrointestinal effects of single and repeated administration of ferrous sulphate was evaluated measuring faecal flora modifications and histology of stomach and duodenum of the rat. The acute experiments showed reversible histopathological lesions of stomach and duodenum with iron deposition and increase in faecal Cl. perfringens toxin after treatment with a high dose of FeSO4. The chronic experiment at lower doses showed no relevant histological damage, some iron deposition and strong alterations in faecal flora. A strong impact of oral FeSO4 on gastrointestinal environment was demonstrated.

[In vivo and in vitro experimentation with the effects of chlorhexidine in patients who have undergone a periodontal intervention]. / Sperimentazione in vivo ed in vitro degli effetti della clorexidina in pazienti sottoposti ad intervento parodontale.

The periodontal pack is often used to cover the surgical site after surgery, even when associated with local applications of preparations containing chlorexidine, in order to obtain an antiseptic protection. However many people question whether the drug effectively succeeds in penetrating the pack, or if the presence of the pack itself doesn't obstruct the action of the medication. The aim of this work is to evaluate the efficiency of the clorexidine in the surgical area with and without a periodontal pack. In a first stage, a case was chosen and contemporary operated on in two different but anatomically similar sites at the same time. One of the two sites was covered with a chlorexidine gel for the following week, whilst the other was left without medication. After seven days the stitches removed from the two different sites were placed in culture mediums to number and classify the bacterial strains present. In the second stage of the experiment, another eight patients were operated on in the same way, and the two sites covered with periodontal packs. In one of the two sites a layer of chlorexidine gel was positioned under the pack, and the chlorexidine above and on the sides of the pack was continually renewed throughout the week following the operation. The other site was not treated. The results obtained show that the pack partially reduces the action of the drug medication, probably because an insufficient amount reaches the site. The activity and efficiency of chlorexidine against the strains of bacteria found in vivo were tested in vitro. The chlorexidine destroyed all of them.(ABSTRACT TRUNCATED AT 250 WORDS)

Desferrioxamine potentiated SOD antiinflammatory activity in rat adjuvant arthritis: role of iron and bacterial toxins.

In this paper we studied the modulating inflammatory activity of iron in the adjuvant arthritis, taking indomethacin as a standard antiinflammatory drug and a superoxide dismutase derivative (MPEG-SOD) as a scavenger of free radicals. Moreover, we evaluated the changes in potential intestinal pathogens requiring iron for growth, in order to study the role of bacteria in the altered gastrointestinal functions observed during arthritis. We observed a 50% arthritis inhibition on the 14th day with MPEG-SOD plus desferrioxamine, a significant decrease in serum iron in arthritic rats compared to controls, and a significant Cl. perfringens increase on the 28th day in the presence of MPEG-SOD. Our data demonstrate that hypoferremia, in arthritis, is a protective mechanism overall in the early phase and could protect the intestinal tract by inhibiting the development of potential pathogens.