Enhanced plant tolerance to iron starvation by functional substitution of chloroplast ferredoxin with a bacterial flavodoxin

Iron limitation affects one-third of the cultivable land on Earth and represents a major concern for agriculture. It causes decline of many photosynthetic components, including the Fe-S protein ferredoxin (Fd), involved in essential oxidoreductive pathways of chloroplasts. In cyanobacteria and some algae, Fd down-regulation under Fe deficit is compensated by induction of an isofunctional electron carrier, flavodoxin (Fld), a flavin mononucleotide-containing protein not found in plants. Transgenic tobacco lines expressing a cyanobacterial Fld in chloroplasts were able to grow in Fe-deficient media that severely compromised survival of WT plants. Fld expression did not improve Fe uptake or mobilization, and stressed transformants elicited a normal deficit response, including induction of ferric-chelate reductase and metal transporters. However, the presence of Fld did prevent decrease of several photosynthetic proteins (but not Fd) and partially protected photosynthesis from inactivation. It also preserved the activation state of enzymes depending on the Fd-thioredoxin pathway, which correlated with higher levels of intermediates of carbohydrate metabolism and the Calvin cycle, as well as increased contents of sucrose, glutamate, and other amino acids. These metabolic routes depend, directly or indirectly, on the provision of reduced Fd. The results indicate that Fld could compensate Fd decline during episodes of Fe deficiency by productively interacting with Fd-dependent pathways of the host, providing fresh genetic resources for the design of plants able to survive in Fe-poor lands.     

Improved metabolic profile after switch to darunavir/ritonavir in HIV positive patients previously on protease inhibitor therapy

Metabolic abnormalities associated with cumulative exposure to antiretroviral therapy have been linked to an increased risk of myocardial infarction in HIV positive individuals. The aim of this study was to evaluate whether the switch from lopinavir/ritonavir (LPV/r) or fosamprenavir/ritonavir (FPV/r) to darunavir/ritonavir (DRV/r) is able to improve the lipid profile. A total of 13 Caucasian subjects (7 from LPV/r and 6 from FPV/r) were enrolled in the study and received DRV/r at the dose of 800/100 mg, without change in their NRTI backbone. Viro‐immunological parameters, triglycerides (TGs), total cholesterol (TCh), high‐density lipoprotein (HDL) and low‐density lipoprotein (LDL) cholesterol, fasting glucose, HOMA‐IR, indexes of hepatic and renal functionality, microalbuminuria and cystatin C were measured at baseline (T0), 3 months (T3), 6 months (T6), and 12 months (T12). The switch to DRV/r reduced levels of TCh, LDL, and TGs at T3. Similar improvements were confirmed further at T6 and at T12. A 14% increase in CD4+ count cells (P < 0.05) was observed. Serum cystatin C values showed a statistically significant decrease. After 12 months of switching to DRV/r from LPV/r or FPV/r, patients infected with HIV with TGs above 200 mg/dl, showed a 49% decrease in TGs, along with a 16% reduction of LDL and 19% reduction of TCh. Switching to DRV/r also improved immunological parameters, such as CD4+ cells count and cystatin C plasmatic levels, which may translate into a reduction of the cardiovascular risk. In conclusion, a switch to DRV/r should be considered in those HIV positive patients undergoing antiretroviral therapy, who also present abnormal lipid profiles. J. Med. Virol. 85:755–759, 2013. © 2013 Wiley Periodicals, Inc.     

VM26 in malignant hematological diseases

Summary From August 1979 to April 1981, 33 consecutive patients with malignant hematological diseases, entered this phase II study. Sixteen patients had NHL, eight CLL, four Myeloma, three HD, one ALL, and one Polycythaemia vera. Two patients were unevaluable because of early death. The median age was 67 years. Eight patients were not pretreated with drugs. Two CR (5+, 20+ weeks) were obtained among NHL patients, whereas five PR were observed among two NHL, one CLL, one Myeloma, and one HD patients, respectively. Toxicity was almost exclusively hematologic and occurred in ten patients, in one of them causing severe myelosuppression. Moreover, severe asthenia, attributable to VM26, was encountered in three patients, in one requiring the suspension of the treatment.     

Treatment with silybin-vitamin E-phospholipid complex in patients with hepatitis C infection

The aim of this study was to evaluate the hepatoprotective and anti-inflammatory effects of silybin-phospholipids and vitamin E complex (SPV complex), by determining cytokine patterns and various markers of liver disease. Forty Caucasian patients with chronic HCV infection were recruited and divided into two groups: 30 were treated with SPV complex for 3 months, while the other 10 did not receive any treatment. Ten other subjects without HCV infection but with staeatosic diagnosis were recruited and treated with SPV complex. Biochemical and hepatic principal parameters were investigated at 0 (T0) and 3 months (T3). The group of HCV patients treated showed an improvement trend of hepatic indecises and viral load, and had a significant and persistent reduction of ALT (P = 0.02) and AST serum level (P = 0.01). In this group cytokines showed a statistically significant increase of IL-2 (P = 0.03) and IL-6 were significantly reduced (P = 0.02) at T0 and T3. After the treatment the group of hepatic steatosics showed a significant decrease in ALT (P = 0.02), AST (0.008), gammaGT (0.004) alkaline phosphatase (0.05), total cholesterol (P = 0.03), fasting glucose (P = 0.008), insulinemia (0.0006), HOMA value (0.002) and C-reactive protein (CRP; 0.04). There was a significant reduction of IFN-gamma, TNF-alpha, and IL-6 (P = 0.02, 0.05 and 0.04, respectively). The data suggest that the SPV complex exerts hepatoprotective, anti-inflammatory and antifibrotic effects. This new compound may therefore be useful in clinical practice in patients with chronic hepatitis C who cannot undergo conventional antiviral therapy.