1. Wei Sheng Yan Jiu. 2013 Mar;42(2):277-81.

[Be based on the morphological and histological changes to study optimal dose of TCDD induced cleft palate in mice embryo]. He X, Liu C, Pu Y, Gan L, Yuan X, Wei G, Fu Y. Source : http://www.ncbi.nlm.nih.gov/pubmed/23654107 Plastic Surgery of Chongqing Medical University Affiliated Children's Hospital, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing 40014, China. xiaomengyouyou@126.com Abstract OBJECTIVE: To define the optimal 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD) dose based on the morphological and histological changes of fetal mice cleft palate induced by different TCDD doses. METHODS: The pregnant mice were randomly divided into five groups and 6 in each grouop, and were gavaged on gestation day 10 (GD10). The control group were given 0.1 ml corn oil, and the experimental groups I, II , III, IV were given 32, 28, 24, 20 microg/kg TCDD respectively. To weight pregnant mice and embryos, record the number of live, cleft palate, dead and resorption fetal mice on GD 17.5. Another 15 pregnant mice were randomly divided into five groups (same as above) and 3 in each group. The coronal sections of the fetal mice heads were prepared at GD 13.5, 14.5 and 15.5 respectively, stained with haematoxylin-eosin staining (HE) and observed by microscopy. RESULTS: No significant differences in embryonic weight and live fetuses weight in each group. Compared with the control group,experimental groups I - III had small palate shelves (PS) and delayed palae shelves lift; the palate development and elevation in experimental group IV was similar to the control group. The incidence of cleft palate in the experimental groups I - IV were 97.37%, 93.02%, 65.12%, 56.82%, and no cleft palate in the control group. CONCLUSION: The optimal dose of TCDD to induce cleft palate in C57BL/6J mice is 28 microg/kg.
Plant Foods Hum Nutr. 1998;52(4):315-24.

Supplementary effect of spirulina on hematological status of rats during pregnancy and lactation.
Kapoor R, Mehta U. Source : http://www.ncbi.nlm.nih.gov/pubmed/10426118
Department of Home Science, Sri Sathya Sai Institute of Higher Learning Anantapur, Andhra Pradesh, India.

Abstract
The effect of Spirulina on iron status was assessed based on hemoglobin, packed cell volume, serum iron, total iron binding capacity and ferritin levels of rats during pregnancy and lactation. Rats were fed 5 different kinds of diets (casein, Spirulina, wheat gluten, Spirulina + wheat gluten, Spirulina without additional vitamins and minerals) each providing 22 percent protein. Diets containing Spirulina alone or in combination with wheat gluten resulted in significantly higher iron storage and hemoglobin contents than casein and wheat gluten diets during the first half of pregnancy and lactation. Wheat gluten diet result in the smallest increase in hemoglobin levels and iron stores compared to other diets. The values of serum iron and iron binding capacity remained unchanged with different diets. Spirulina appears to be effective in improving the iron status of rats during pregnancy and lactation.

1. Wei Sheng Yan Jiu. 2013 Mar, 42 (2) :277-81. [Be didasarkan pada perubahan morfologi dan histologi untuk mempelajari dosis optimal TCDD diinduksi sumbing pada tikus embrio]. Ia X, Liu C, Pu Y, Gan L, Yuan X, Wei G, Fu Y. Sumber: http://www.ncbi.nlm.nih.gov/pubmed/23654107 Bedah Plastik Rumah Sakit University Medical Afiliasi Anak, Departemen Pendidikan Kunci Laboratorium Perkembangan Anak dan Gangguan, Chongqing 40.014, Cina Chongqing. xiaomengyouyou@126.com Abstrak TUJUAN: Untuk menentukan optimal 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD) dosis didasarkan pada perubahan morfologi dan histologi dari janin tikus sumbing disebabkan oleh dosis TCDD berbeda. METODE: Tikus-tikus hamil secara acak dibagi menjadi lima kelompok dan 6 di setiap grouop, dan gavaged pada umur kebuntingan 10 hari (GD10). Kelompok kontrol diberi 0,1 ml minyak jagung, dan kelompok eksperimen I, II, III, IV diberi 32, 28, 24, 20 microg / kg TCDD masing-masing. Untuk bobot tikus hamil dan embrio, mencatat jumlah hidup, sumbing, mati dan resorpsi tikus janin pada GD 17,5. Lain 15 tikus hamil secara acak dibagi menjadi lima kelompok (sama seperti di atas) dan 3 di masing-masing kelompok. Bagian koronal dari janin tikus kepala disiapkan di GD 13.5, 14.5 dan 15.5 masing-masing, diwarnai dengan hematoksilin-eosin (HE) dan diamati dengan mikroskop. HASIL: Tidak ada perbedaan signifikan dalam berat embrio dan janin hidup berat dalam setiap kelompok. Dibandingkan dengan kelompok kontrol, kelompok eksperimen I III memiliki rak kecil langit-langit (PS) dan tertunda palae rak angkat, pengembangan palatum dan elevasi di kelompok eksperimen IV mirip dengan kelompok kontrol. Insiden bibir sumbing dalam kelompok eksperimen I - IV adalah 97.37%, 93.02%, 65.12%, 56.82%, dan tidak ada langit-langit pada kelompok kontrol. KESIMPULAN: Yang optimal dosis TCDD untuk menginduksi sumbing pada tikus C57BL/6J adalah 28 microg / kg.

Tanaman Foods Hum Nutr. 1998; 52 (4) :315-24. Efek Tambahan spirulina status hematologi tikus selama kehamilan dan menyusui. Kapoor R, Mehta U. Sumber: http://www.ncbi.nlm.nih.gov/pubmed/10426118 Departemen Dalam Ilmu, Sri Sathya Sai Institute of Higher Learning Anantapur, Andhra Pradesh, India. Abstrak Pengaruh Spirulina status besi dinilai berdasarkan hemoglobin, volume yang dikemas sel, besi serum, kapasitas total pengikatan zat besi dan tingkat feritin tikus selama kehamilan dan menyusui. Tikus-tikus diberi 5 jenis diet (kasein, Spirulina, gluten gandum, Spirulina + gluten gandum, Spirulina tanpa tambahan vitamin dan mineral) masing-masing memberikan 22 persen protein. Diet yang mengandung Spirulina sendiri atau dalam kombinasi dengan gluten gandum mengakibatkan penyimpanan zat besi secara signifikan lebih tinggi dan isi hemoglobin daripada kasein dan gluten gandum diet selama paruh pertama kehamilan dan menyusui. Gluten gandum hasil diet dalam kenaikan terkecil dalam kadar hemoglobin dan zat besi dibandingkan dengan diet lainnya. Nilai-nilai besi serum dan kapasitas pengikatan besi tetap tidak berubah dengan diet yang berbeda. Spirulina tampaknya efektif dalam meningkatkan status zat besi tikus selama kehamilan dan menyusui.

Pencarian 1

Mechanism of cleft palate in mice induced by 2, 3, 7, 8tetrachlorodibenzo-p-dioxin].

[Article in Chinese]

Pu YL, Liu LL, Gan LQ, He XM, Fu YX. Source

Chongqing Children's Hospital, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, Chongqing Medical University, Chongqing 400014, China.

Abstract
OBJECTIVE: To explore the mechanism of cleft palate in mice induced by 2, 3, 7, 8-Tetrachlorodibenzo-p-dioxin (TCDD). METHODS: On gestation day 10 (GD 10), 12 pregnant mice were randomly divided into two groups as the treated group and the control group with 6 mice in each group. The mice in the treated group received intragastric administration with 64 microg TCDD/kg, while the mice in the control group received equivalent corn oil. The embryos were examined under stereomicroscope to detect the incidence of cleft palate on GD 18.5. Another 18 pregnant mice were randomly divided into two groups (treated group and control group) on GD 10 with 9 pregnant mice in each group. Then each group was divided into 3 subgroups: GD 13.5, GD 14.5 and GD 15.5, with 3 pregnant mice in each subgroup. The palatal shelves were dissected from the embryos for RNA and DNA extraction on GD 13.5, GD 14.5 and GD 15.5. At last the expression of Smad 2-4 and Smad 7 mRNA was investigated by RT-PCR, and the TGF-beta3 promoter methylamine levels were investigated by methylation specific PCR (MSP). RESULTS: The cleft palate mice model was established successfully by exposing pregnant C57BL/6J mice to TCDD. Total frequency of clefts was 100% in TCDD group, and the frequency of clefts was 0 in the control group. The relative expression of Smad 2 mRNA was 0.263 +/- 0.088, 0.296 +/- 0.016 and 0.159 +/- 0.027 in TCDD group, 0.180 +/- 0.042, 0.282 +/- 0.029 and 0.165 +/- 0.018 in control group. The relative expression of Smad 3 mRNA was 0.453 +/- 0.153, 0.551 +/- 0.160 and 0.328 +/- 0.049 in TCDD group, 0.375 +/- 0.126, 0.510 +/- 0.145 and 0.259 +/- 0.035 in control group. The relative expression of Smad 4 mRNA was 0.675 +/- 0.174, 0.577 +/- 0.070 and 0.396 +/- 0.066 in TCDD group, 0.557 +/- 0.138, 0.587 +/- 0.080 and 0.441 +/- 0.054 in control group. The relative expression of Smad 7 mRNA was 0.283 +/-

0.050, 0.320 +/- 0.068 and 0.169 +/- 0.045 in TCDD group, 0.207 +/- 0.043, 0.288 +/- 0.051 and 0.155 +/0.040 in control group. There was no significant difference between the TCDD treated mice and the control (P > 0.05). The TGF-beta3 promoters were at the un-methylation state both in the TCDD treated and control group. CONCLUSION: It suggests that TCDD could induce a stable formation of cleft palate, but it is not through the TGFbeta/Smad signaling nor through the modification of TGF-beta3 promoter methylation.
PMID:

22292409 [PubMed - indexed for MEDLINE]

Pencarian 2
Scientific Name(s): Arthrospira platensis(Nordstedt) Gomont and Arthrospira maximaSetchell et Gardner. Family: Phormidiaceae Common Name(s): Spirulina , dihe , tecuitlatl

Uses of Spirulina
Spirulina is sold in the United States as a health food or supplement. Diverse claims exist for its immunostimulatory, hypolipidemic, antiviral, and anticancer effects; however, there is limited evidence to support these indications.

Spirulina Dosing
Doses in clinical studies have ranged from 1 to 10 g/day.

Contraindications
Phenylketonuria; however, this has not been substantiated.

Pregnancy/Lactation
Information regarding safety and efficacy in pregnancy and lactation is lacking. Because of possible mercury and other heavy metal contamination, spirulina should be avoided during pregnancy.

Spirulina Interactions
None well documented.

Spirulina Adverse Reactions

Few reports of adverse reactions are available. However, spirulina-associated hepatotoxicity and reactions from heavy metal contamination are possible.

Toxicology
Spirulina is considered nontoxic to humans at usual levels of consumption; however, information is limited. Spirulina, a blue-green algae (cyanophytes/cyanobacteria), grows as microscopic, corkscrewshaped multicellular filaments and is now classified as a distinct genus, Arthrospora . A. plantensis is found in Africa and Asia, and A. maxima is found in Central America. 1 , 2 Free growing, spirulina exists only in high-salt alkaline water in subtropical and tropical areas, sometimes imparting a darkgreen color to bodies of water. 3 Spirulina is noted for its characteristic behavior in carbonated water and energetic growth in laboratory cultures. 4 It is commercially grown in the United States and has been proposed as a primary foodstuff to be cultivated during long-term space missions because it withstands extreme conditions. 5 , 6 Due to its unique growth requirements, contamination of open pond cultures of spirulina by other microorganisms is usually slight, with the alga growing as a relatively pure culture.

History
Spirulina has been described in literature since the 16th century. Spanish explorers observed the Aztecs harvesting a blue mud that probably consisted of spirulina. 2 The mud, which was dried to form chips or flavored loaves, was obtained from Lake Texcoco near Mexico City. Spirulina was similarly harvested in the Sahara Desert from small lakes near Lake Chad, where it was called dihe . Thus, 2 cultures approximately 10,000 km apart, independently discovered and utilized the nutritional properties of spirulina. 2 Currently, spirulina is actively marketed by numerous companies as a nutritional supplement. 7

Chemistry
Spirulina is composed of approximately 65% crude protein, high levels of B-complex vitamins, 8vitamin E, 9 beta-carotene, 10 and zeaxanthin. 4 , 11 The protein content includes 22 essential amino acids, 2 , 12 and the total protein is nutritionally superior to legume protein, but inferior to meat protein. 2 The proteins C-phycocyanin and allophycocyanin in spirulina have been the focus of much research. 13 , 14 High levels of gamma linolenic acid, a polyunsaturated fatty acid, are present. 15 An assay for spirulina lipids using high-pressure liquid chromatography-mass spectrometry has been developed. 16 Spirulina preparations contain 300 to 400 ppm iron (dry weight), and unlike many forms of plant iron, has high bioavailability when ingested by humans. A dosage of 10 g/day can contain 1.5 to 2 mg of absorbable iron, similar to that of standard ferrous sulfate. 17 , 18 Trace elements present at high levels include manganese, selenium, and zinc. Calcium, potassium, and magnesium are also concentrated in the organism. 19 Calcium spirulan, a sulfated polysaccharide, was characterized from A. platensis . 20

Spirulina Uses and Pharmacology

Clinical trials have investigated spirulina's potential but have been too small to support its purported effects. 21 Allergic rhinitis and asthma Experimental data have suggested that C-phycocyanin can selectively inhibit release of histamine from mast cells and prevent increases in immunoglobulin E. A small study in patients with mild to moderate asthma suggested that spirulina supplementation (1 g/day) produced improvement in lung function parameters, 22 while a study evaluating spirulina in allergic rhinitis suggested a positive effect on laboratory values, but no clinical outcomes were reported. 23 A 6-month, double-blind, placebo-controlled study enrolling 150 patients with allergic rhinitis found efficacy for 2 g/day of spirulina over placebo using diary-based symptom scores of nasal discharge. 24 Antimicrobial activity A provocative suggestion has been made that human cultures in which large amounts of algae are consumed have lower levels of HIV infection. 25 Spirulina and its extracts have been evaluated for antiviral activity. One in vitro study found that the sulfated polysaccharide calcium spirulan interfered with the replication of several enveloped viruses, including herpes simplex, cytomegalovirus, mumps, measles, influenza A, and HIV-1, 20 while another study described a slightly different range of viruses susceptible to the extract. 26 HIV-1 adsorption and penetration were inhibited by an aqueous extract of spirulina, while a crude hot water extract reduced HIV-1 replication. 25 This type of in vitro activity is common to acidic polysaccharides from a variety of sources. Enterovirus is also susceptible to spirulina, and allophycocyanin was the active constituent. 27 Spirulina demonstrated some in vitro activity against common human bacterial pathogens but less than that of the standard comparator. 28 Immune stimulation by phycocyanin and polysaccharides of spirulina led to an antifungal and antibacterial effect in mice. 29 Cancer C-phycocyanin showed a dose-dependent inhibition of HeLa and human chronic myeloid leukemia cell growth and proliferation in vitro. 30 , 31 Induction of apoptosis was considered to be one of the mechanisms involved. 32 Doxorubicin-resistant HepG2 liver cancer cells were inhibited by spirulina C-phycocyanin through an apoptotic mechanism, 33 while water-soluble polysaccharides were implicated as the active agent against stomach cancer cells. 34 A combination of selenium and spirulina inhibited MCF-7 breast cancer cells via growth arrest and apoptosis. 35 Survival rates increased in mice with liver cancer treated with C-phycocyanin, and tumor regression has been reported in animals with oral cancer. 36 , 37 , 38 Activation of antitumor natural killer cells by spirulina enhanced antitumor efficacy in a B16 mouse melanoma model, and the effect was abolished in MyD88 null/null mice, indicating that NK cell activation was a key pathway. 39 In a hamster cheek pouch model of carcinogenesis, 10 mg/day of spirulina extract reduced dysplastic changes, 40 which was further confirmed by an immunohistochemical study. 41 Spirulina was chemopreventative in a dibutyl nitrosamine carcinogenesis model. 42 It also induced lesion regression in tobacco chewers with oral leukoplakia in a study conducted in India. 43 Diabetes

A study in alloxan-induced diabetic rats revealed that spirulina at 10 mg/kg orally for 30 days lowered glucose levels, while slightly elevating insulin. 44 Two small clinical studies investigated the effects of spirulina supplementation in type 2 diabetes, with improvement noted in fasting blood sugar and lipid profiles. Suggested mechanisms of action include hypoglycemia caused by fiber content or possible insulin-stimulating action of peptides and polypeptides of spirulina proteins. The actions on lipids have been attributed to gamma linolenic acid content. 45 , 46 Dietary supplement Spirulina, considered a food item for centuries in many countries, is now popularly thought of as a dietary supplement. 5 Spirulina consumption was purported to aid in weight loss because of its high phenylalanine content, but a US Food and Drug Administration review found no evidence to support this claim. 47 , 48 Suggestions that spirulina is a valuable source of vitamin B 12 have been similarly disputed. 5 Skeletal muscle protein (myosin) was increased in young rats fed spirulina as the sole dietary protein source compared with casein. 49 A study of spirulina supplementation for 8 weeks demonstrated clinical improvement in weight gain and increased hemoglobin levels in malnourished children in the West African nation of Burkina Faso. 50 Similar results have been demonstrated among children who are HIV-positive. 51 In elderly Koreans, spirulina 8 g/day for 16 weeks had a variety of positive effects (cholesterol, antioxidant status, interleukin [IL]-2 and IL-6 levels) observed in a randomized, double-blind, placebo-controlled study. 52 In a study of athletic training, spirulina increased time to fatigue, decreased carbohydrate oxidation rate, and increased fat oxidation rate, leading to an increase in exercise performance. 53 Hyperlipidemia Experiments in rats suggest that C-phycocyanin exhibits hypercholesterolemic action. 54 In rabbits fed a high-cholesterol diet, spirulina (1% or 5% in diet) lowered serum triglycerides, total cholesterol, and low-density lipoprotein (LDL) at 8 weeks. High-density lipoprotein (HDL) was markedly increased. 55 Two small clinical studies examined the role of spirulina in hyperlipidemia secondary to nephrotic syndrome. Both populations showed an improved lipid profile with spirulina supplementation; however, the control group in 1 experiment also showed improvement. The gamma linolenic acid content of spirulina may have played a role in the mechanism of action.56 , 57 A study in type 2 diabetes patients reported a reduction in triglycerides with 8 g/day of spirulina. 58 In normal volunteers, 4.5 g/day of spirulina for 6 weeks lowered blood pressure, total cholesterol, LDL, and increased HDL. 59 , 60 Immune system effects Most in vitro and animal experiments have suggested immunostimulatory effects; however, 1 study found a spirulina extract to be immunosuppressive. 61 Activation of monocytes and macrophages, 62 , 63 as well as augmentation of interleukin and interferon production, have been demonstrated. 64 Intestinal epithelial lymphocytes of aged mice treated with spirulina were increased compared with the control aged group. 65 A clinical study in healthy men found that oral administration of spirulina for 3 months resulted in enhanced interferon production and natural killer (NK) cell capacity. 25 An ex vivo study of NK cells from spirulina-treated healthy patients showed increased NK activity, which was confirmed by a second study in which NK cell and T-cell markers were increased by spirulina. 66 A clinical trial in elderly patients showed positive effects on anemia and immunosenescence after 6 and 12 weeks of supplementation. 67The immunostimulatory effects appear to be largely mediated by spirulina polysaccharides. 62 ,63

Prevention of toxicity due to metals or organic compounds A 5% spirulina-supplemented diet prevented carbon tetrachloride-induced fatty liver in rats. 68 In a case series of 3 patients with nonalcoholic fatty liver disease, 4.5 g/day of spirulina for 3 months improved ALT values and lipid profiles. 69 Cadmium toxicity in rats was reduced by spirulina, as measured by liver histopathology. 70 Mercuric chloride-induced oxidative stress in mice was blocked by spirulina at 800 mg/kg orally for 40 days. 71 Lead acetate damage to rats was minimized by spirulina via normalizing plasma and liver lipid levels, as well as via its antioxidant effect. 72 A protein extract and purified phycocyanin protected neuroblastoma cells from iron-induced toxicity. 73 Spirulina pretreatment protected mice against acetaminophen and galactosamineinduced liver damage. 74 Liver and kidney enzyme markers of toxicity were reduced by spirulina following 4-nitroquinoline 1-oxide insult to rats. 75 Spirulina decreased cisplatin-induced nephrotoxicity in rats, an effect attributed to an antioxidant action. 76Gentamicin-induced kidney damage in rats was reversed by intraperitoneal spirulina 1 g/kg daily.77 In pregnant mice, teratogenicity due to cadmium was reduced by 125 to 500 mg/kg of spirulina by intragastric administration for 17 days of gestation. 78 Mutagenicity of cyclophosphamide in mice pretreated with spirulina was reduced. 79 In a small, randomized, placebo-controlled trial, spirulina plus zinc increased urinary excretion of arsenic and decreased arsenic hair-content in people with long-term exposure to arsenic. 80 Antioxidant The spirulina protein phycocyanin in pure form was active in 4 different cell-free radical-scavenging assays; however, phycocyanin-containing selenium was more effective. 81 In cellular assays of antioxidant activity, 4 commercial spirulina preparations were also active. 82 Spirulina supplementation of rats did not increase plasma or liver alpha-tocopherol levels 83 ; however, another study reported effective antioxidant activity using combinations of whey protein and spirulina. 84 C-phycocyanin from spirulina reduced oxidative stress in hamsters fed an atherogenic diet. 85 Similarly, rabbits fed a high-cholesterol diet were protected from oxidative stress by 4 to 8 weeks of spirulina in feed at 1% or 5%. 86 Other studies suggest spirulina as an antioxidant, 87 but clinical importance has not been demonstrated, 88 , 89 and 1 small clinical study showed spirulina to be without effect on plasma antioxidant status. 90 Other uses C-phycocyanin inhibited platelet aggregation in ex vivo experiments. 91 In mice with zymosaninduced arthritis, phycocyanin exerted a scavenging action against reactive oxygen species and antiinflammatory activity. 92 Similar experiments with complete Freund's adjuvant-induced arthritis found 800 mg/kg of oral spirulina effective in reducing inflammation. 93 In rats, collagen-induced arthritis was inhibited by 400 mg/kg of spirulina. 94 Osteoporosis was inhibited in rosiglitazone-treated rats by 500 mg/kg/day of oral spirulina. 95 A rat study showed evidence that spirulina could protect neural stem cells and promote their growth 96 ; however, an amyotrophic lateral sclerosis (ALS) support network did not find the evidence compelling for use in ALS. 97Spirulina supplementation (3 g/day) was ineffective against idiopathic chronic fatigue in a small study. 98 Pretreatment with spirulina 180 mg/kg orally in a rat cerebral ischemia-reperfusion injury model reduced neurologic deficits and histological changes. 99 A polysaccharide extract of spirulina was antiangiogenic in a mouse corneal model. 100 Spirulina also has been reported to protect mouse and human bone marrow cells against gamma radiation. 23 , 76 , 87 , 101 , 102 ,103

Dosage
There is insufficient clinical data to guide dosing of spirulina for therapeutic effect. Spirulina has typically been studied in daily dosage of 1 to 10 g. 22 , 50

Pregnancy/Lactation
Information regarding safety and efficacy in pregnancy and lactation is lacking. Spirulina may contain more than 180 mcg of mercury per 20 g 19 and should be avoided.

Interactions
None well documented. An antiplatelet effect has been demonstrated in vitro but was not clinically evaluated. 91

Adverse Reactions
Few reports of adverse reactions are available. Case reports of immunoblistering 104 and rhabdomyolysis 105 linked to spirulina have been published. Cyanobacteria (blue-green algae) may contain the amino acid phenylalanine; therefore, people with phenylketonuria should avoid spirulina. 5 A case of spirulina-associated hepatotoxicity has been reported. 106 Hepatotoxic microcystins and neurotoxic anatoxin-a are produced by a number of cyanobacteria and have been reported as spirulina contaminants. 107 , 108 Other contaminants include the heavy metals mercury, cadmium, arsenic, and lead, as well as microbes cultivated on fermented animal waste.19 , 109 Questions have been raised regarding the potential for adverse reactions in people with autoimmune disorders who consume immunostimulatory herbal preparations. 110

Toxicology
Spirulina is considered nontoxic to humans at usual amounts of consumption; however, information is limited.

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