The effect of intravenous infusion of N-acetyl cysteine in cirrhotic patients undergoing liver resection: A randomized controlled trial.

BACKGROUND AND AIMS: Liver resection can lead to hepatocellular dysfunction. The aim was to evaluate the effect of N-acetyl cysteine (NAC) on liver enzymes (alanine aminotransferase [ALT] and aspartate aminotransferase [AST]), international normalized ratio (INR), C-reactive protein (CRP), and intercellular adhesion molecule 1 (ICAM 1) in cirrhotic patients undergoing liver resection. MATERIAL AND METHODS: A randomized controlled trial (RCT), Pan African Clinical Trial registry (PACTR201508001251260). 60 Child A patients were studied. NAC group (n = 30) received intravenous infusion of NAC 10 g/24 h in 250 ml of 5% dextrose during surgery and for 2 days. Controls (C) (n = 30) received a similar volume of 5% dextrose. All above parameter were measured during and after surgery. RESULTS: ALT and AST were significantly elevated after surgery, but to a less extent with NAC versus C (day 3; 118.3 ± 18.6 vs. 145.4 ± 14.0 U/L. P < 0.01) and (121.5 ± 19.5 vs. 146.6 ± 15.1 U/L, P = 0.00), respectively. Lower serum CRP and ICAM 1 with NAC versus C on day 3 (44.2 ± 13.4 vs. 68.7 ± 48.2 mg/l, P = 0.003), (308.8 ± 38.2 vs. 352.8 ± 59.4 ng/ml, P = 0.002), respectively. Hospital stay was shorter with NAC versus C (6.1 ± 0.8 vs. 6.9 ± 1.2 days, P = 0.006). Duration of surgery, INR, and hemodynamics were comparable. CONCLUSION: Prophylactic NAC in hepatic patients undergoing liver surgery attenuated postoperative increase in transaminases, ICAM 1, and CRP blood levels. The impact of these findings and the cost benefit of reduced hospital stay on enhanced recovery after surgery needs to be evaluated.

Alpha-amylase inhibitory activity of two Anthocleista species and in vivo rat model anti-diabetic activities of Anthocleista djalonensis extracts and fractions.

ETHNOPHARMACOLOGICAL RELEVANCE: Anthocleista djalonensis (A. Chev) and Anthocleista vogelii Planch are plants being used in West Africa traditionally to treat various diseases such as malaria, hernia, hypertension, stomach aches, hemorrhoids, syphilis, and diabetes. Diabetes causes about 5% of all deaths globally each year. Chemotherapeutic agents such as biguanides, sulfonylureas, and thiozolidinediones are available for the treatment of diabetes, however, they have undesirable side effects. The need for newer, more effective and less toxic drugs is imperative and the biodiversity of Nigeria has a high potential for drug discovery based on plants used in the ethnomedicine. AIM OF THE STUDY: To investigate the leaves, stem bark and roots of these plants for their probable alpha-amylase inhibitory activities and establish their anti-diabetic activities. The overall goal is do bioassay-guided fractionation and isolation of active anti-diabetic compounds. MATERIALS AND METHODS: Powdered samples (leaves, stem bark and roots) macerated with 80% aqueous methanol were evaluated in vitro using alpha-amylase inhibitory assay while in vivo investigations were carried out on hyperglycemic rats. Diabetes was induced in albino rats by an intraperitoneal injection of alloxan monohydrate (80mg/kg). Plant extracts (1g/kg) were given orally for 7 days, while blood glucose levels were monitored using a one touch glucometer. The crude methanol extracts found to be most active were further partitioned into hexane and ethyl acetate fractions which were also tested in vivo on the diabetic animals. RESULTS: The leaves and stem bark crude methanol extracts of Anthocleista djalonensis gave comparable α-amylase inhibition of 73.66% and 72.90%, respectively which were quite higher than the 38.93% and 22.90% of the same plant parts given by Anthocleista vogelii. The crude stem bark extract of Anthocleista djalonensis exhibited significant peak blood glucose reduction on day 6 (72.59%, p<0.05) which was higher than the leaves or roots which gave 45.73% and 47.46% (p<0.05), respectively The stem bark ethyl acetate fraction of Anthocleista djalonensis gave reduction in blood glucose level of 60.86% (p<0.05). CONCLUSION: From our results, the leaves, stem bark and whole root of both plants exhibited α-amylase inhibitory activities with Anthocleista djalonensis also showing good anti-diabetic activities in vivo indicating that they contain active principles for the management of diabetes. There is justification for the use of the plants traditionally to manage diabetes.

So near and yet so far: the specific case of Ralstonia Solanacearum populations from Côte d'Ivoire in Africa.

The genetic and phenotypic diversity of Côte d'Ivoire Ralstonia solanacearum strains was assessed on a 168-strain collection sampled on Solanaceae both in the southern lowlands and western highlands. Phylotypes I, II, and III were prevalent, though at unexpected frequencies. Phylotype I strains (87.5%) were genetically diverse and overrepresented in all agroecological areas, including highlands (AEZ III). Phylotype II strains (10.7%) only belonged to one tropical lowland-adapted broad host range lineage (IIA-35), whereas no highland-adapted potato brown rot (IIB-1) or Moko strains were detected. African phylotype III strains were rare (1.8%). They originated from a single Burkina Faso lineage (III-23) and were only found in lowlands. Three phylotype I strains were found harboring pRSC35, a plasmid identified in phylotype III strains in Cameroon. From pathogenicity tests performed on commercial varieties and tomato/eggplant/pepper references, the virulence diversity observed was high, with five pathoprofiles described. Eggplant accessions MM152 and EG203 and tomato HW7996 displayed the largest resistance spectrum and highest level. Two highly virulent phylotype I strains were able to bypass resistance of HW7996 and the eggplant reference AG91-25. Collectively, these points lead to the conclusion that the situation in Côte d'Ivoire is specific towards other African countries, and specifically from the Cameroon reference, and that within phylotype I can exist a high virulence diversity. This calls for similar studies in neighboring West African countries, linking R. solanacearum pathogen genetic diversity to strain virulence at the regional level, for the rationalization of regional resistance deployment strategies and future resistance durability studies.

First Report of Zucchini yellow mosaic virus in Cucurbits in Ivory Coast.

During a field survey conducted in December 2008 and January 2009 in southern Ivory Coast, zucchini squash (Cucurbita pepo L.) and cucumber (Cucumis sativus L.) plants were observed showing severe symptoms of leaf mosaic and distortions, filiformism, and fruit deformations. Nine samples were collected from symptomatic plants in four locations (Adzopé, Songon, Ayamé, and Gagnoa) and dried over CaCl2. Double-antibody sandwich (DAS)-ELISA tests were performed directly on dried samples with antisera against nine cucurbit-infecting viruses: Zucchini yellow mosaic virus (ZYMV, Potyvirus); Papaya ringspot virus (PRSV, Potyvirus); Watermelon mosaic virus (WMV, Potyvirus); Moroccan watermelon mosaic virus (MWMV, Potyvirus); Cucumber vein yellowing virus (CVYV, Ipomovirus); Cucumber mosaic virus (CMV, Cucumovirus); Cucurbit aphid borne yellows virus (CABYV, Polerovirus); Squash mosaic virus (SqMV, Comovirus); and Cucumber green mottle mosaic virus (CGMMV, Tobamovirus). ZYMV was detected alone in four of six zucchini squash samples and in mixed infection with CMV and PRSV in two of three cucumber samples. A cucumber sample (CI09-09) collected at Songon and infected by ZYMV, CMV, and PRSV was inoculated to zucchini squash. ZYMV was separated from CMV and PRSV by inoculating zucchini squash plantlets with one Myzus persicae Sulzer per plant with 2-min acquisition and 2-h inoculation access periods. Plants infected by ZYMV only developed typical symptoms of severe mosaic, distortion, and filiformism on leaves. Total RNA was extracted from the original dried sample of CI09-09 using TRI-Reagent (Molecular Research Center Inc., Cincinnati, OH) (2). One-step reverse transcription (RT)-PCR was performed with our standard protocol and specific primers (2), yielding a 605-bp fragment corresponding to part of the polymerase (NIb) and coat protein (CP) coding regions. The nucleotide sequence of the NIb-CP fragment of Ivory Coast ZYMV isolate CI09-09 (GenBank No. HM450303) shared 98.5, 92.7, 80.5, and 75.7% identity with ZYMV isolates from France (isolate E9, HM641798), Florida (D13914), Singapore (AF014811), and Vietnam (DQ925449), respectively. Sequence comparison indicated that CI09-09 belongs to the phylogenetic cluster 1 of group A of ZYMV (2). ZYMV, first described in 1981, is now one of the most damaging viruses in cucurbit crops worldwide and is characterized by an important biological and molecular diversity (1,3). ZYMV has already been reported in several African countries, mostly in the northern and southern parts of the continent (1), but to our knowledge, this is the first report of ZYMV in Ivory Coast. Among African isolates, CI09-09 shared 97.5% identity with isolate Su06-22 from Sudan (HM641799) belonging to the phylogenetic cluster 1 of group A of ZYMV, 94 to 95% identity with isolates from neighboring Mali (HM005307-HM005312) belonging to cluster 2 of group A, and 79.6% identity with the divergent isolate R5A from Réunion Island (L29569) belonging to phylogenetic group B of ZYMV. The presence of ZYMV in four distant locations in southern Ivory Coast suggests that this virus constitutes a serious threat to cucurbit production in this country. References: (1) C. Desbiez and H. Lecoq. Plant Pathol. 46:809, 1997, (2) C. Desbiez et al. Virus Res. 85:5, 2002, (3) H. Lecoq et al. Virus Res. 141:190, 2009.

Wound healing effect of Flabellaria paniculata leaf extracts.

AIM OF THE STUDY: This study evaluated wound healing activity of the chloroform and aqueous fractions of the methanolic extract of Flabellaria paniculata leaf on infected wounds in rats as a follow up to an initial study of the crude extract. MATERIALS AND METHODS: Wounds were inflicted on Wistar rats using excision model. Local infection was introduced into rat abdominal wounds with Staphylococcus aureus and Pseudomonas aeruginosa using a 10(8)cells/ml inoculum. Rate of wound healing was assessed by contraction and period of epithelization. RESULTS: Chloroform fraction exhibited significant wound healing potency (p<0.05) as compared with controls. The test drug achieved 100% wound contraction on day 14 in non-infected group, on day 16 in Staphylococcus aureus infected group and on day 18 in Pseudomonas aeruginosa group. CONCLUSIONS: Chloroform extract of Flabellaria paniculata proves to be a potential anti-infective and wound healing agent. Its in vitro antibacterial and in vivo wound healing activities are in good agreement with the local medicinal use of the plant for skin diseases and sores.

Hypoglycaemic and amylase inhibitory activities of leaves of Spondias mombin Linn.

Suppressing the production of glucose by inhibiting a-amylase / a-glucosidase activity is one of the therapeutic approaches for decreasing postprandial hyperglycaemia and a strategy for evaluating antidiabetic activity. We investigated leaves of Spondias mombin because our previous ethnobotanical survey showed that it is used by traditional healers to manage diabetes in South West Nigeria. We report a bioactivity-guided study of S. mombin using glucose loading (1 g/kg) alloxan-induced diabetic rats and inhibition of a-amylase as basis for isolation of active constituents. Hyperglycaemia was induced in albino rats and blood glucose levels monitored for 180 mins using a glucometer. Powdered leaves were macerated with 80% Methanol. The active extract was fractionated on column chromatography packed with silica gel G6OA eluting with gradient mixtures of pet. ether and ethylacetate. The most active a-amylase inhibiting fraction was purified on thin layer chromatography (TLC) and pure compound identified by spectroscopy. Peak decrease in blood glucose of 41.4% (p < 0.05) was recorded after 60 mins. This activity-guided study produced an active TLC band (69.8% amylase inhibition, p < 0.05) from which a-sitosterol was characterized as the main inhibitor. This is first report of hypoglycaemic and amylase inhibitory activities of S. mombin. The role of phytosterols in control of diabetes mellitus is discussed. This study justifies the ethnopharmacological use of this species in recipes for management of diabetes mellitus.

Ethnobotanical studies of medicinal plants used in the management of diabetes mellitus in South Western Nigeria.

This survey was carried out in targeted areas of South West Nigeria in order to inventory plants used by traditional healers in the area for the management of diabetes mellitus. One hundred traditional healers who know and use medicinal plants for treating diabetes mellitus were interviewed. The inventory contains scientific, vernacular, common names of the plants used and method of preparation. Thirty-one plants commonly used by traditional healers in the region were identified. The survey shows plants from the Rutaceae, Leguminosae and Cucurbitaceae families are commonly used by traditional healers in South West Nigeria for the treatment of diabetes mellitus.

Isolation of an anti-tumour terpenoid from stem bark of Spondianthus preussii var. preussii Engl.

We report a biologically monitored phytochemical separation of stem bark of Spondianthus preussii var. preussii against a panel of human cancer cell lines in vitro and the P-388 murine lymphocytic leukemia cells in culture. An ethylacetate extract of the stem bark exhibited selective cytotoxicity against human melanoma (ED50 = 10.0 ug/ml). Further activity-guided fractionation of the ethylacetate extract by flash chromatography and subsequent purification on preparative thin layer chromatography led to the identification of a lupane-type triterpene, 3beta-hydroxy-20(29)--lupenoic acid, by spectroscopic methods. This is the first report of the occurrence of this compound in S. preussii var. preussii. It is also the first time this triterpene is being shown to exhibit in vitro anti-tumor activity against human melanoma (ED50 = 2.4 ug/ml). This compound could be a promising bioactive natural product since it has been previously reported to exhibit a range of biological activities including in vivo and in vitro antiplasmodial activity and it is not toxic.

Seasonal accumulation of anthraquinones in leaves of cultivated Cassia podocarpa Guill et Perr.

Seasonal variations and spectrophotometric determination of anthraquinones in cultivated Cassia podocarpa are presented. The study shows that combined anthraquinones are concentrated in the leaves at peak flowering (2.43%) and lowest in the bark (0.21%). Anthraquinone glycosides reached peak levels during the months of October to March (dry season), the maximum being recorded during January to March. There was significant drop in glycosidic content during the period April to September (rainy season). There was slight increase in concentration of aglycones during the rainy season which may be due to inter-conversion of some glycosides to the aglycones. However, the free aglycone content is much lower than the glycosides. This is desirable for optimum laxative activity and reduced toxicity. This study is significant because it provides useful information on the seasonal distribution of anthraquinones and the best period for harvesting leaves of C. podocarpa for drug development. The inclusion of C. podocarpa in the African Pharmacopoeia will, no doubt, enhance its commercialization as laxative and for its antimicrobial effect.

[Blood concentrations and side effects of tacrolimus in a living renal transplantation].

In a living renal transplantation, the recipients are administered an immunosuppressive agent preoperatively. The drug exhibits a high incidence of side effects of special note. We examined the side effects of tacrolimus to evaluate the postoperative management of living renal transplantation. Hypertension, hyperglycemia, tachycardia and chest pain were found as the side effects. The blood concentration should be measured frequently to maintain the effective blood concentration and to prevent the side effect.

[Behavior of Trp-P-1 and its metabolites in rat excreta].

To study of the behavior of Trp-P-1 and its metabolites in rat feces and urine, rats were orally administered with Trp-P-1 (750, 1,500 and 2,500 micrograms/rat), and excreted Trp-P-1 was analyzed using HPLC assay and bacterial mutagenicity assay. The extraction of Trp-P-1 from urine was performed by using the chloroform extraction method, and blue rayon was used for the extraction from feces. When Trp-P-1 was added to rat feces and urine, the recoveries of Trp-P-1 were 85.9 +/- 3.9% and 91.3 +/- 3.7%, respectively. The extracts of feces and urine from rats administered with Trp-P-1 were individually fractionated by thin layer chromatography on C18 gel. The major mutagenic zone corresponding to Trp-P-1 was found at Rf 0.09 in both extracts, while the feces extract gave two additional mutagenic zones at Rf 0.15 and 0.20. More than 97% of the fecal mutagenic activity was due to unchanged Trp-P-1. In rats administered with 750 micrograms of Trp-P-1, the amount of extracted Trp-P-1 and the number of His+ colonies induced by whole excreta were 81.6 +/- 7.1 micrograms (n = 6) and (432 +/- 77) x 10(4) for feces, and 28.7 +/- 4.9 micrograms and (171 +/- 28) x 10(4) for urine. The recoveries of Trp-P-1 in the feces and urine were 10.8 +/- 0.9% and 3.8 +/- 0.7% by HPLC analysis, and 11.1 +/- 2.0% and 4.4 +/- 0.7% by mutagenicity assay respectively. The results of the two assays seemed to show similar patterns of recovery.

Microscopic evaluation and seasonal variations of anthraquinone glycosides of cultivated Cassia fistula Linn.

In this report, we present the results of the microscopy, seasonal variations and spectrophotometric estimation of hydroxy-anthraquinone glycosides of culitivated Cassia fistula Linn. The total glycoside contents ofthe morphological parts of this species at different stages of growth are also presented. The study shows that anthraquinone glycosides are concentrated in the leaves (1.75%) and flowers (1.58%) at peak flowering. Notable seasonal variations were observed in the cultivated species. Hydroxyanthraquinones reached peak levels druing the months of September (1.08%) and October (2.20%). There was a significant drop (P < 0.05) in glycoside content during most part of the rainy season. It has been established that anthraquinone glycosides, rather than the aglycones, are the active forms and hence an estimation of the total glycoside content of a sample is a reliable indication of biological activity. The advantages of using the natural anthraquinone laxative when the glycoside content is highest are discussed. The study has provided useful information on the best period for harvesting the morphological parts of C. fistula for drug development.

Comparative analysis of plasma and erythrocyte 7-ketocholesterol as a marker for oxidative stress in patients with diabetes mellitus.

OBJECTIVES: To reveal increased lipid peroxidation in diabetics by quantification of cholesterol oxidation products (COPs) not only in plasma, but also in erythrocytes. DESIGN AND METHODS: We quantified 7-ketocholesterol (7-kCho) by gas chromatography-mass spectrometry as a surrogate measure for COPs. These assays were performed on both plasma and erythrocytes in 20 control subjects and 20 treated patients with relatively poorly controlled Type 2 diabetes. RESULTS: Both plasma and erythrocyte 7-kCho levels in diabetics were significantly higher than those in control subjects. Although neither plasma nor erythrocyte 7-kCho levels were associated with markers for glucose tolerance in diabetics, a negative correlation of serum HDL-cholesterol levels with erythrocyte, but not plasma, 7-kCho levels was found. CONCLUSION: Increased oxidative stress in diabetics affects oxidation of cholesterol. Assays of COPs not only in plasma, but also in erythrocytes, may yield complementary information in lipid peroxidation.

Seasonal variations of hydroxyanthraquinone content of cultivated Cassia spectabilis DC.

Seasonal variations and spectrophotometric estimation of the anthraquinone content of cultivated Cassia spectabilis DC are presented. Concentrations of anthraquinones peaked in the leaves (1.03%) at flowering Significant (P < 0.05) variations in anthraquinone content were observed in the cultivated species. Anthraquinones reached peak levels during the months of September to January (dry season). There was a significant (P < 0.05) drop in anthraquinone content during the rainy season. The diagnostic microscopic features of this little studied species are also described. This study has provided vital information on the best period of harvest and seasonal distribution of anthraquinones in the leaves of the species.

Antimicrobial potential of Spondias mombin, Croton zambesicus and Zygotritonia crocea.

The antimicrobial activity of Spondias mombin, Croton zambesicus and Zygotritonia crocea sourced from herbalists through an ethnobotanical survey of Egbado-South in Ogun State in Nigeria is reported. The extracts of the leaf of Spondias mombin and the stem bark of Croton zambesicus exhibited wide spectrum antibacterial effects comparable to those of ampicillin and gentamycin. The antifungal effect of extracts of Zygotritonia crocea and Croton zambesicus were comparable to those of tioconazole. There is justification for the use of these little studied medicinal plants as antiinfective agents in traditional medicine.

Antimicrobial screening of Bridelia, micrantha, Alchormea cordifolia and Boerhavia diffusa.

This report is on the antimicrobial potential of Bridelia micrantha, Alchornea cordifolia and Boerhavia diffusa sourced from traditional healers through an ethnobotanical survey of antiinfective plants in Egbado South in Ogun State, Nigeria. Extracts of B. micrantha and A. cordifolia exhibited significant inhibitory activity against the pathogenic organisms. In some cases, the antibacterial activity was comparable to those of ampicillin and gentamycin. However, only the leaf of A. cordifolia showed reasonable antifungal activity when compared with Trosyd. The study shows that there is justification for the use of these medicinal plants in traditional medicine.

21-Hydroxylase deficiency presenting as massive bilateral adrenal masses in the seventh decade of life.

A 72-year-old woman was found to have massive bilateral adrenal masses on computed tomography and was diagnosed with 21-hydroxylase deficiency (21-OHD) based on endocrinological findings. Physical examination revealed no abnormalities except markedly short stature. She was diagnosed with 21-OHD because she had an elevated serum 17alpha-hydroxyprogesterone (17-OHP) level which significantly decreased in response to dexamethasone. Percutaneous CT-guided biopsy and later autopsy confirmed that the adrenal masses were due to adrenocortical hyperplasia. Analysis of the CYP21 gene revealed that the patient was a compound heterozygote for the Ile-172-->Asn mutation in exon 4 and the 8-bp deletion in exon 3. Simple virilizing 21-OHD (SV) would be predicted from this genotype. She had few symptoms associated with 21-OHD except for markedly short stature, but the serum 17-OHP level was higher than that of typical nonclassical form of 21-OHD and near to that of typical SV. This finding was confirmed by analysis of the CYP21 gene. From these results, we report that when adrenal masses are incidentally detected, 21-OHD should be ruled out to avoid excessive examination and surgery on the suspicion of adrenal carcinoma.

A novel single basepair insertion in exon 6 of the Bruton's tyrosine kinase (Btk) gene from a Japanese X-linked agammaglobulinemia patient with growth hormone insufficiency.

A novel insertion mutation in exon 6 of the Btk gene was detected in a 17 year-old XLA patient with GH insufficiency. We synthesized cDNA from leukocyte total RNA and amplified every region of the Btk-coding sequence. Sequencing of cDNA fragments revealed a single basepair insertion mutation at codon 157 in exon 6 (CAG-->CAAG) which leads to premature termination at codon 193 in exon 7. To confirm the results, we also performed a PCR-DdeI digestion analysis using leukocyte genomic DNA. The PCR product from the patient's genomic DNA was uncleaved with DdeI, as expected. PCR-DdeI digestion analysis of the family members showed that the mother and elder sister were carriers with the mutation and that the younger sister did not carry the mutation.

The effect of probucol on oxidized cholesterol disposition in hyperlipidaemic patients.

Probucol is a cholesterol-lowering and antioxidant drug that has been shown to inhibit or delay the progression of atherosclerosis. This antiatherosclerotic effect may result from the removal of oxidized cholesterol on the surface of low-density lipoprotein (LDL). To investigate whether probucol transfers oxidized cholesterol from LDL to urine, urine samples were obtained from five patients with hypercholesterolaemia treated with 500-mg probucol orally daily and from five healthy controls. Using gas chromatography-mass spectrometry, we identified cholesteryl-6-(2,6-di-tertiary butylphenol-4)-thioether (CT) in the urine samples from patients with hypercholesterolaemia but not from healthy controls. This result suggests that probucol is hydrolysed to form 4-mercapto-2,6-di-tertiary butylphenol (MBP) which conjugates with cholesterol-5 alpha, 6 alpha-epoxide, oxidized cholesterol, resulting in the formation of CT in vivo. In addition to its hypolipidaemic and antioxidant actions, probucol may act to prevent atherosclerosis by increasing the urinary excretion of oxidized cholesterol.