Brain grey matter abnormalities in medication-free patients with major depressive disorder: a meta-analysis.

BACKGROUND: Because cerebral morphological abnormalities in major depressive disorder (MDD) may be modulated by antidepressant treatment, inclusion of medicated patients may have biased previous meta-analyses of voxel-based morphometry (VBM) studies. A meta-analysis of VBM studies on medication-free MDD patients should be able to distinguish the morphological features of the disease itself from those of treatment. METHOD: A systematic search was conducted for the relevant studies. Effect-size signed differential mapping was applied to analyse the grey matter differences between all medication-free MDD patients and healthy controls. Meta-regression was used to explore the effects of demographics and clinical characteristics. RESULTS: A total of 14 datasets comprising 400 medication-free MDD patients and 424 healthy controls met the inclusion criteria. The pooled meta-analysis and subgroup meta-analyses showed robustly reduced grey matter in prefrontal and limbic regions in MDD. Increased right thalamus volume was only seen in first-episode medication-naive patients, and increased grey matter in the bilateral anterior cingulate cortex only in medication wash-out patients. In meta-regression analyses the percentage of female patients in each study was negatively correlated with reduced grey matter in the right hippocampus. CONCLUSIONS: By excluding interference from medication effects, the present study identified grey matter reduction in the prefrontal-limbic network in MDD. The subgroup meta-analysis results suggest that an increased right thalamus volume might be a trait directly related to MDD, while an increased anterior cingulate cortex volume might be an effect of medication. The meta-regression results perhaps reveal the structural underpinning of the sex differences in epidemiological and clinical aspects of MDD.

Vitamin D deficiency induces Th2 skewing and eosinophilia in neonatal allergic airways disease.

BACKGROUND: Associations between vitamin D status and childhood asthma are increasingly reported, but direct causation and mechanisms underlying an effect remain unknown. We investigated the effect of early-life vitamin D deficiency on the development of murine neonatal allergic airways disease (AAD). METHODS: In utero and early-life vitamin D deficiency was achieved using a vitamin D-deficient diet for female mice during the third trimester of pregnancy and lactation. Offspring were weaned onto a vitamin D-deficient or vitamin D-replete diet, and exposure to intranasal house dust mite (HDM) or saline was commenced from day 3 of life for up to 6 weeks, when airway hyper-responsiveness (AHR), airway inflammation and remodelling were assessed. RESULTS: Neonatal mice that had in utero and early-life vitamin D deficiency had significantly increased pulmonary CD3(+) CD4(+) T1ST2(+) cells and reduced CD4(+) IL-10(+) cells. This effect was enhanced following HDM exposure. AHR in HDM-exposed mice was unaffected by vitamin D status. Introduction of vitamin D into the diet at weaning resulted in a significant reduction in serum IgE levels, reduced pulmonary eosinophilia and peri-bronchiolar collagen deposition. CONCLUSION: Peri-natal vitamin D deficiency alone has immunomodulatory effects including Th2 skewing and reduced IL-10-secreting T regulatory cells, exaggerated with additional allergen exposure. Vitamin D deficiency in early life does not affect AHR, but contributes to disease severity with worse eosinophilic inflammation and airway remodelling. Importantly, supplementation with vitamin D improves both of these pathological abnormalities.

Synergistic effects of diosmetin with erythromycin against ABC transporter over-expressed methicillin-resistant Staphylococcus aureus (MRSA) RN4220/pUL5054 and inhibition of MRSA pyruvate kinase.

Increasing prevalence of methicillin-resistant Staphylococcus aureus (MRSA) worldwide with limited therapeutic options is a growing public health concern. Natural products have been shown to possess antibacterial actions against MRSA. Flavonoids from natural products have been shown to possess antibacterial actions against MRSA by antagonizing its resistance mechanisms. Diosmin and diosmetin are natural flavonoids found in a variety of citrus fruits. The aim of this study was to investigate whether diosmin and diosmetin could inhibit the growth of MRSA and the in vitro enzymatic activity of a newly discovered MRSA drug target, pyruvate kinase (PK). By using a panel of MRSA strains with known resistant mechanisms, neither diosmin nor diosmetin was shown to possess direct antibacterial activities against all tested MRSA strains. However, in checkerboard assay, we found that diosmetin together with erythromycin, could synergistically inhibit the growth of ABC-pump overexpressed MRSA-RN4220/pUL5054, and time kill assay also showed that the antibacterial activities of diosmetin with erythromycin were bactericidal. Diosmetin was further shown to significantly suppress the MRSA PK activities in a dose dependent manner. In conclusion, the inhibition of MRSA PK by diosmetin could lead to a deficiency of ATP and affect the bacterial efflux pump which might contribute to the antibacterial actions of diosmetin against MRSA.

Synergistic effects of baicalein with ciprofloxacin against NorA over-expressed methicillin-resistant Staphylococcus aureus (MRSA) and inhibition of MRSA pyruvate kinase.

ETHNOPHARMACOLOGICAL RELEVANCE: Baicalein, the active constituent derived from Scutellaria baicalensis Georgi., has previously been shown to significantly restore the effectiveness of ß-lactam antibiotics and tetracycline against methicillin-resistant Staphylococcus aureus (MRSA). With multiple therapeutic benefits, the antibacterial actions of baicalein may also be involved in overcoming other bacterial resistance mechanisms. The aim of the present study was to further investigate antibacterial activities of baicalein in association with various antibiotics against selected Staphylococcus aureus strains with known specific drug resistance mechanisms. MATERIAL AND METHODS: A panel of clinical MRSA strains was used for further confirmation of the antibacterial activities of baicalein. The effect of baicalein on inhibiting the enzymatic activity of a newly discovered MRSA-specific pyruvate kinase (PK), which is essential for Staphylococcus aureus growth and survival was also examined. RESULTS: In the checkerboard dilution test and time-kill assay, baicalein at 16 µg/ml could synergistically restore the antibacterial actions of ciprofloxacin against the NorA efflux pump overexpressed SA-1199B, but not with the poor NorA substrate, pefloxacin. Moreover, synergistic effects were observed when baicalein was combined with ciprofloxacin against 12 out of 20 clinical ciprofloxacin resistant strains. For MRSA PK studies, baicalein alone could inhibit the enzymatic activity of MRSA PK in a dose-dependent manner. CONCLUSION: Our results demonstrated that baicalein could significantly reverse the ciprofloxacin resistance of MRSA possibly by inhibiting the NorA efflux pump in vitro. The inhibition of MRSA PK by baicalein could lead to a deficiency of ATP which might further contribute to the antibacterial actions of baicalein against MRSA.

[Further investigation on Second Volume of Essay on Simple Recipe and Pulsology (SESR) and Wang's Simple Recipes (WSR)].

There are 2 extant editions of SESR, written in Chunyou Jiachen (1244) reign. In the facsimile copy of Song manuscript recorded in Kojima's Records of Investigating Ancient Classics which was brought by Yang Shoujing and is now collected in the Library of Palace Museum in Taipei. There is also a facsimile copy of Song dynasty postscribed by Taki Genkan now collected in Library of Relics and Naturalist Academy of National Imperial Secretariat in Japan. The book is written in one volume, dealing first with four diagnostic methods, followed by drug and therapy and compounding of recipes and "processing" of drugs, thus forming a complete system. The WSR included in Classified Collection of Recipes is not the Essay on Pulsology, neither WANG Shou's Simple Recipes, but Yi jian gui yi (Unity of Simplicity and Easiness) by XU Ruoxu of Yuzhang, Jiangxi of Yuan dynasty, being an epitomized work of all physicians of Yongjia medical schools with only 3 pieces of incomplete papers remained.

Correction of anemia using self-administered daily subcutaneous erythropoietin in uremic patients on continuous ambulatory peritoneal dialysis.

We studied the effects of self-administered, daily, low-dose, subcutaneous (SC) erythropoietin (EPO) therapy in 15 uremic patients on continuous ambulatory peritoneal dialysis (CAPD) for 16 weeks to assess its efficacy and safety. The patients had baseline hemoglobin (Hb) levels of < 8 g/dl and were started on 10 u/kg/day of beta-EPO. The dosage of EPO was adjusted every 4 weeks according to hematological response. The patients learned to inject into their thighs themselves. Hb increased significantly from 6.6 +/- 0.2 g/dl (mean +/- SEM) at week 0 to 9.0 +/- 0.3 at week 8 and 10.0 +/- 0.4 at week 16 (p < 0.0001). Hematocrit (Hct) increased significantly from 0.20 +/- 0.01 at week 0 to 0.27 +/- 0.01 at week 8 and 0.29 +/- 0.001 at week 16 (p < 0.0001). The mean EPO dose was 10 u/kg/day at week 0 and 10.5 +/- 0.4 at week 8 and 10.3 +/- 0.5 at week 16. After minor adjustments in antihypertensive therapy had been made no significant differences in mean arterial blood pressure were noted. Six of 15 patients required increased dosage of antihypertensive drugs. All patients were given oral iron supplements. There was a significant decrease in percentage of transferrin saturation and 10 patients required additional intravenous iron supplements. There was no significant difference in the serum levels of creatinine, albumin, potassium, phosphate and urate with EPO treatment. There were no local complications at the sites of injection and the injections themselves were quite painless.(ABSTRACT TRUNCATED AT 250 WORDS)

Vitamin D status of Hong Kong Chinese infants.

Vitamin D deficiency is a common nutritional problem of weaning infants in many parts of the world. Hong Kong infants, who are fed with traditional rice-based weaning foods and live in crowded high rise flats, might be expected to suffer from this nutritional problem. Yet a study of 150 bottle fed infants revealed that the vitamin D intake from fortified milk and cereals was more than half of the recommended amount throughout the first 18 months and that the serum 25-OH vitamin D concentration of the infants at 18 months was normal. The effect of sunlight was also evident.

Dietary fish oil supplements preserve renal function in renal transplant recipients with chronic vascular rejection.

The effect of dietary fish oil supplements on renal failure and lipid abnormalities was studied in 14 adult renal transplant recipients with chronic vascular rejection. The rate of decline of renal function (assessed by studying the slope of reciprocal plasma creatinine plots) slowed significantly during a 6-month period on fish oil supplements compared with the preceding 6-month control period (slope 1/cr during supplementation -3.6 X 10(-5) mumols/l per month compared with -13.5 X 10(-5) before, the difference in slope being -9.8 X 10(-5), 95% confidence interval (CI) -16.2 X 10(-5), -3.5 X 10(-5), P less than 0.05). Total plasma triglyceride concentrations decreased during supplementation (mean change -1.15 mmol/l, 95% CI -1.84, -0.47, P less than 0.003), but there was no change in total plasma cholesterol concentration or urinary protein excretion. Platelet function was studied in nine patients. Platelet aggregation induced by adrenaline and collagen was reduced by fish oils (median change in per cent aggregation), adrenaline 2 mumols/l, -36% (95% CI -68%, -8%, P less than 0.05), collagen 1 mg/1, -13% (95% CI -44%, -2%, P less than 0.05). Platelet thromboxane A2 release in response to these agents was also significantly reduced. These results demonstrate that fish oils preserve residual function in renal graft failure due to chronic vascular rejection.

Traditional Chinese infant supplementary medical foods given by mothers in Hong Kong.

Chinese mothers living in Hong Kong are used to giving their babies special medicinal food to strengthen the infant's internal defences and to restore the body's harmonious state. However since the majority of registered doctors are trained in the Western pharmacological tradition it is difficult for them to comprehend the concepts and idioms of this practice. This paper set out to investigate the frequency and varieties of medicinal foods given to 166 Chinese infants during the first 30 months after birth. One hundred and forty seven babies were given medicinal foods at some stage. The frequency of their administration varied from weekly to once or twice per month. The most popular medicinal food was "Job's tears" and the most widely administered compound herb preparations were milk preparation solution, flower teas and various cool teas. The potential pharmacological effects of these medicinal foods were searched from a Chinese medicines computerized database and found to be principally anti-inflammatory, bacteriostatic, diuretic and appetite stimulant. This study contributed a better appreciation of the popularity of infant supplementary medicinal foods in Hong Kong and the rationale for their use.