Garlic extract induces intestinal P-glycoprotein, but exhibits no effect on intestinal and hepatic CYP3A4 in humans

Garlic extracts have been shown to decrease drug exposure for saquinavir, a P-glycoprotein and cytochrome P450 3A4 substrate. In order to explore the underlying mechanisms and to study the effects of garlic on pre-systemic drug elimination, healthy volunteers were administered garlic extract for 21 days. Prior to and at the end of this period, expression of duodenal P-glycoprotein and cytochrome P450 3A4 protein were assayed and normalized to villin, while hepatic cytochrome P450 3A4 function and simvastatin, pravastatin and saquinavir pharmacokinetics were also evaluated. Ingestion of garlic extract increased expression of duodenal P-glycoprotein to 131% (95% CI, 105-163%), without increasing the expression of cytochrome P450 3A4 which amounted to 87% (95% CI, 67-112%), relative to baseline in both cases. For the erythromycin breath test performed, the average result was 96% (95% CI, 83-112%). Ingestion of garlic extract had no effect on drug and metabolite AUCs following a single dose of simvastatin or pravastatin, although the average area under the plasma concentration curve (AUC) of saquinavir decreased to 85% (95% CI, 66-109%), and changes in intestinal P-glycoprotein expression negatively correlated with this change. In conclusion, garlic extract induces intestinal expression of P-glycoprotein independent of cytochrome P450 3A4 in human intestine and liver.

[Acrodermatitis enteropathica-like skin lesions due to Crohn's disease-associated zinc deficiency]

We report a case of acrodermatitis enteropathica-like skin eruptions presenting with alopecia, perlèche, glossitis, and genital erosions as well as multifocal eczematoid, psoriasiform, and bullous skin lesions due to zinc deficiency in Crohn's disease.

Trigonal and peritrigonal lesions of the lateral ventricle-surgical considerations and outcome analysis of 20 patients

The aim of this study is to review the results and clinical outcome of patients with surgically treated lesions within the trigone of the lateral ventricle. This is a retrospective case series of 20 (eight male, 12 female) patients with lesions of the trigone of the lateral ventricle operated between 1998 and 2008. All lesions were removed via the transcortical temporal and transcortical parietal route. Surgical complications and outcome were assessed using the modified Rankin Scale (mRS). There were four children and 16 adults with a mean age of 42?±?22 years (min?=?1, max?=?74). Eight (40%) lesions grew within the trigone of the dominant hemisphere. In 17 cases, the lesion was purely intraventricular, and in three cases, a slight paraventricular extension was seen. The mean size was 4.5 cm of maximal diameter. Surgical removal was achieved via the transcortical parietal route in 13 cases (65%) and the transcortical temporal route in seven cases (35%). In all cases, complete resection was possible. According to the mRS, 13 patients improved, five remained the same, and two were lost to follow-up. One patient had an increased visual field deficit postoperatively and new hemiparesis and aphasia, but returned to the preoperative level within a few weeks. In one patient, an acute myocardial infarction occurred due to previous cardiac stent placement and in-stent stenosis. Even large trigonal lesions can be resected with low morbidity using a transcortical approach depending on the peritrigonal extension of the tumor.

Reduction in hepatic drug metabolizing CYP3A4 activities caused by P450 oxidoreductase mutations identified in patients with disordered steroid metabolism

Cytochrome P450 3A4 (CYP3A4), the major P450 present in human liver metabolizes approximately half the drugs in clinical use and requires electrons supplied from NADPH through NADPH-P450 reductase (POR, CPR). Mutations in human POR cause a rare form of congenital adrenal hyperplasia from diminished activities of steroid metabolizing P450s. In this study we examined the effect of mutations in POR on CYP3A4 activity. We used purified preparations of wild type and mutant human POR and in vitro reconstitution with purified CYP3A4 to perform kinetic studies. We are reporting that mutations in POR identified in patients with disordered steroidogenesis/Antley-Bixler syndrome (ABS) may reduce CYP3A4 activity, potentially affecting drug metabolism in individuals carrying mutant POR alleles. POR mutants Y181D, A457H, Y459H, V492E and R616X had more than 99% loss of CYP3A4 activity, while POR mutations A287P, C569Y and V608F lost 60-85% activity. Loss of CYP3A4 activity may result in increased risk of drug toxicities and adverse drug reactions in patients with POR mutations.

Use of combined liothyronine and thyroxine therapy for consumptive hypothyroidism associated with hepatic haemangiomas in infancy

Hepatic haemiangiomas in infancy are rare. An association with hypothyroidism has been previously reported and is believed to be secondary to the conversion of thyroxine (fT4) to biologically inactive reverse triiodothyronine (rT3) by type 3 iodothyronine deiodinase (D3). We report a case that responded well to the combined use of liothyronine and thyroxine therapy.

Effects of catecholamines on hepatic and skeletal muscle mitochondrial respiration after prolonged exposure to faecal peritonitis in pigs

Use of norepinephrine to increase blood pressure in septic animals has been associated with increased efficiency of hepatic mitochondrial respiration. The aim of this study was to evaluate whether the same effect could be reproduced in isolated hepatic mitochondria after prolonged in vivo exposure to faecal peritonitis. Eighteen pigs were randomized to 27 h of faecal peritonitis and to a control condition (n = 9 each group). At the end, hepatic mitochondria were isolated and incubated for one hour with either norepinephrine or placebo, with and without pretreatment with the specific receptor antagonists prazosin and yohimbine. Mitochondrial state 3 and state 4 respiration were measured for respiratory chain complexes I and II, and state 3 for complex IV using high-resolution respirometry, and respiratory control ratios were calculated. Additionally, skeletal muscle mitochondrial respiration was evaluated after incubation with norepinephrine and dobutamine with and without the respective antagonists (atenolol, propranolol and phentolamine for dobutamine). Faecal peritonitis was characterized by decreasing blood pressure and stroke volume, and maintained systemic oxygen consumption. Neither faecal peritonitis nor any of the drugs or drug combinations had measurable effects on hepatic or skeletal muscle mitochondrial respiration. Norepinephrine did not improve the efficiency of complex I- and complex II-dependent isolated hepatic mitochondrial respiration [respiratory control ratio (RCR) complex I: 5.6 ± 5.3 (placebo) vs. 5.4 ± 4.6 (norepinephrine) in controls and 2.7 ± 2.1 (placebo) vs. 2.9 ± 1.5 (norepinephrine) in septic animals; RCR complex II: 3.5 ± 2.0 (placebo) vs. 3.5 ± 1.8 (norepinephrine) in controls; 2.3 ± 1.6 (placebo) vs. 2.2 ± 1.1 (norepinephrine) in septic animals]. Prolonged faecal peritonitis did not affect either hepatic or skeletal muscle mitochondrial respiration. Subsequent incubation of isolated mitochondria with norepinephrine and dobutamine did not significantly influence their respiration.

Expansive nasopalatine duct cysts with nasal involvement mimicking apical lesions of endodontic origin: a report of two cases

The nasopalatine duct cyst (NPDC) is the most frequent nonodontogenic cyst of the jaws and can be misinterpreted as an apical lesion of endodontic origin.

Long-term stability of surgical bone regenerative procedures of peri-implantitis lesions in a prospective case-control study over 3 years

Objectives: To evaluate the extent of bone fill over 3 years following the surgical treatment of peri-implantitis with bone grafting with or without a membrane. Material and Methods: In a non-submerged wound-healing mode, 15 subjects with 27 implants were treated with a bone substitute (Algipore®) alone and 17 subjects with 29 implants were treated with the bone substitute and a resorbable membrane (Osseoquest®). Implants with radiographic bone loss ≥1.8 mm following the first year in function and with bleeding and/or pus on probing were included. Following surgery, subjects were given systemic antibiotics (10 days) and rinsed with chlorhexidine. After initial healing, the subjects were enrolled in a strict maintenance programme. Results: Statistical analysis failed to demonstrate changes in bone fill between 1 and 3 years both between and within procedure groups. The mean defect fill at 3 years was 1.3 ± (SD) 1.3 mm if treated with the bone substitute alone and 1.6 ± (SD) 1.2 mm if treated with an adjunct resorbable membrane, (p=0.40). The plaque index decreased from approximately 40–10%, remaining stable during the following 2 years. Conclusion: Defect fill using a bone substitute with or without a membrane technique in the treatment of peri-implantitis can be maintained over 3 years.

In situ and in vitro comparison of laser fluorescence with visual inspection in detecting occlusal caries lesions

The aim of this study was to compare the in situ and in vitro performances of a laser fluorescence (LF) device (DIAGNOdent 2095) with visual inspection for the detection of occlusal caries in permanent teeth. Sixty-four sites were selected, and visual inspection and LF assessments were carried out, in vitro, three times by two independent examiners, with a 1-week interval between evaluations. Afterwards, the occlusal surfaces were mounted on the palatal portion of removable acrylic orthodontic appliances and placed in six volunteers. Assessments were repeated and validated by histological analysis of the tooth sections under a stereomicroscope. For both examiners, the highest intra-examiner values were observed for the visual inspection when in vitro and in situ evaluations were compared. The inter-examiner reproducibility varied from 0.61 to 0.64, except for the in vitro assessment using LF, which presented a lower value (0.43). The methods showed high specificity at the D(1) threshold (considering enamel and dentin caries as disease). In vitro evaluations showed the highest values of sensitivity for both methods when compared to the in situ evaluations at D(1) and D(2) (considering only dentinal caries as the disease) thresholds. For both methods, the results of sensitivity (at D(1) and D(2)) and accuracy (at D(1)) showed significant differences between in vitro and in situ conditions. However, the sensitivity (at D(1) and D(2)), specificity and accuracy (both at D(1)) of the methods were not significantly different when the same condition was considered. It can be concluded that visual inspection and LF showed better performance in vitro than in situ.

Do mucositis lesions around implants differ from gingivitis lesions around teeth?

The purpose of this review was to compare peri-implant mucositis and gingivitis with respect to the pathogenesis aspects.

Symptoms before periapical surgery related to histologic diagnosis and postoperative healing at 12 months for 178 periapical lesions

To compare the preoperative signs and symptoms with the histologic diagnosis and postoperative healing at 12 months for 178 periapical lesions.