Can dietary fructans lower serum glucose?

Background: Convincing evidence indicates that the consumption of inulin‐type fructans, inulin, and oligofructose has beneficial effects on blood glucose changes in animal models, although data in humans have been considered equivocal. As such, a systematic review of available literature on humans was conducted to evaluate the effectiveness of dietary inulin‐type fructans on serum glucose. Methods: Thirteen eligible randomized controlled trials (RCT), published from 1984 to 2009, were identified using a comprehensive search strategy involving the PubMed, Medline, and Cochrane Library databases. Exclusion criteria, such as the absence of a control group, lack of information on the quantity of inulin‐type fructans used, and lack of glucose values at outcome, were established. Results: Upon review, only four of the 13 trials (31%) showed a decrease in serum glucose concentration and only one of these was statistically significant. The remaining nine trials showed no significant changes in serum glucose concentration. Conclusion: Based on the present systematic review, it does not appear that inulin‐type fructans have a significant lowering effect on serum glucose in humans. More RCT are needed to determine whether inulin‐type fructans, inulin, and oligofructose have beneficial effects on blood glucose in humans.     

Effect of Semecarpus anacardium Linn. nut extract on mammary and hepatic expression of xenobiotic enzymes in DMBA-induced mammary carcinoma

Breast cancer is the major cause of cancer death in women worldwide. Environmental risk factors particularly genotoxic chemicals such as polycyclic aromatic hydrocarbons (PAH) are likely to account for a much higher mortality. Xenobiotic metabolising enzymes in breast tissue are potentially important determinants in both the susceptibility to the mutagenic effects of chemical carcinogens and in the response of breast tumors to chemotherapy. The well known carcinogen 7,12-dimethylbenz(a)anthrazene of PAH family was given (25 mg/ml) orally by gastric intubation to induce mammary carcinoma in Sprague-Dawley rats. Increased level of cytochromes (P₄₅₀, B₅), EROD, PROD activities, Phase I biotransformation enzymes (NADPH-cytochrome (P₄₅₀) reductase, NADPH-cytochrome (b₅) reductase, epoxide hydrolase) and expression of CYP1A1, CYP1A2 and CYP1B1 in liver and breast tissue microsome were documented in DMBA treated group. Phase II enzyme activities (glutathione-S-transferase, gluthatione peroxidase, gluatathione reductase, UDP-glucuronyl transferease) were decreased markedly in cancerous rats. The nut extract of Semecarpus anacardium was administered orally (200 mg/kg body wt/day) to the mammary carcinoma rats for 14 days. Drug treatment restored back the altered Phase I and II biotransformation enzymes thus achieving complete detoxification of the carcinogen. These findings suggest that S. anacardium can effectively modulate the catabolism of xenobiotics in rats.     

Placental production and maternal serum and urine levels of inhibin A and activin A are modified by antihypertensive therapy in hypertensive disorders of pregnancy

Objective  Levels of inhibin A and activin A are raised in pre-eclampsia (PE) but it is not known if antihypertensive therapy can affect their levels. Our aim was to investigate the effect of the antihypertensive drug α-methyldopa on serum, urine and placental concentrations of inhibin A and activin A in women presenting with hypertensive disorders of pregnancy.
Design  This was a cross-sectional study.
Patients  We recruited 65 women presenting with PE, 39 with gestational hypertension (GH) and 104 normotensive controls matched for maternal age, gestational age and parity.
Measurements  Using specific validated ELISAs, serum and urine levels of inhibin A and activin A, and uterine artery Doppler indices, were measured before and 24–48 h after initiating α-methyldopa therapy in women with PE, with GH and controls. Protein extracts were obtained from samples of placental tissue from another group of women with PE, GH and controls for the same analysis.
Results  In PE, but not GH, α-methyldopa therapy was associated with significantly ( P  < 0·05) lower levels of both serum and urine inhibin A and activin A. Similarly, in PE but not GH, α-methyldopa therapy was associated with lower placental levels of both markers ( P  < 0·05). There was no significant difference in pulsatility index following treatment in either PE or GH.
Conclusions  Our data indicate that antihypertensive therapy with α-methyldopa may have an effect on the synthesis and/or release of placental proteins in pregnancies complicated by PE and that this effect may be independent of its known antihypertensive action.     

Breast filariasis diagnosed by fine needle aspiration cytology--a case report

We report a case of female who presented with a lump in the right breast. Fine needle aspiration cytology of lump revealed numerous adult filarial worms. Common habitat of the adult filarial worms is the lymphatic vessels and lymph nodes of limbs and their occurrence in breast is uncommon.     

GDNF rescues hyperglycemia-induced diabetic enteric neuropathy through activation of the PI3K/Akt pathway

Diabetes can result in loss of enteric neurons and subsequent gastrointestinal complications. The mechanism of enteric neuronal loss in diabetes is not known. We examined the effects of hyperglycemia on enteric neuronal survival and the effects of glial cell line-derived neurotrophic factor (GDNF) on modulating this survival. Exposure of primary enteric neurons to 20 mM glucose (hyperglycemia) for 24 hours resulted in a significant increase in apoptosis compared with 5 mM glucose (normoglycemia). Exposure to 20 mM glucose resulted in decreased Akt phosphorylation and enhanced nuclear translocation of forkhead box O3a (FOXO3a). Treatment of enteric neurons with GDNF ameliorated these changes. In streptozotocin-induced diabetic mice, there was evidence of myenteric neuronal apoptosis and reduced Akt phosphorylation. Diabetic mice had loss of NADPH diaphorase-stained myenteric neurons, delayed gastric emptying, and increased intestinal transit time. The pathophysiological effects of hyperglycemia (apoptosis, reduced Akt phosphorylation, loss of inhibitory neurons, motility changes) were reversed in diabetic glial fibrillary acidic protein-GDNF (GFAP-GDNF) Tg mice. In conclusion, we demonstrate that hyperglycemia induces neuronal loss through a reduction in Akt-mediated survival signaling and that these effects are reversed by GDNF. GDNF may be a potential therapeutic target for the gastrointestinal motility disorders related to diabetes.     

Rac GTPases regulate the morphology and deformability of the erythrocyte cytoskeleton

Actin oligomers are a significant structural component of the erythrocyte cytoskeleton. Rac1 and Rac2 GTPases regulate actin structures and have multiple overlapping as well as distinct roles in hematopoietic cells; therefore, we studied their role in red blood cells (RBCs). Conditional gene targeting with a loxP-flanked Rac1 gene allowed Crerecombinase-induced deletion of Rac1 on a Rac2 null genetic background. The Rac1(-/-);Rac2(-/-) mice developed microcytic anemia with a hemoglobin drop of about 20% and significant anisocytosis and poikilocytosis. Reticulocytes increased more than 2-fold. Rac1(-/-);Rac2(-/-) RBCs stained with rhodamine-phalloidin demonstrated F-actin meshwork gaps and aggregates under confocal microscopy. Transmission electron microscopy of the cytoskeleton demonstrated junctional aggregates and pronounced irregularity of the hexagonal spectrin scaffold. Ektacytometry confirmed that these cytoskeletal changes in Rac1(-/-);Rac2(-/-) erythrocytes were associated with significantly decreased cellular deformability. The composition of the cytoskeletal proteins was altered with an increased actin-to-spectrin ratio and increased phosphorylation (Ser724) of adducin, an F-actin capping protein. Actin and phosphorylated adducin of Rac1(-/-);Rac2(-/-) erythrocytes were more easily extractable by Triton X-100, indicating weaker association to the cytoskeleton. Thus, deficiency of Rac1 and Rac2 GTPases in mice alters actin assembly in RBCs and causes microcytic anemia with reticulocytosis, implicating Rac GTPases as dynamic regulators of the erythrocyte cytoskeleton organization.