Background: Hepatocellular carcinoma (HCC) is the most common type of liver malignancies. Yet, the outcome of the traditional chemotherapeutic agents in the management of HCC still unsatisfactory, most probably due to their limited therapeutic efficacies. Thus, there is an urgent medical need for alternative therapeutic approaches for fighting HCC. Aim: our study aimed at evaluating the possible synergistic antitumor activity of the herbal alkaloid berberine (BER) with the conventional doxorubicin (DOX) in a DENA-induced HCC rat model. Methods: HCC was induced in male Wistar rats by oral DENA administration in their drinking water (100 mg/L) for 8 weeks. In addition to a positive and negative control groups, a group of animals (10 rats) was given DOX (4× 2.5 mg/kg, i.v., weekly). Another group (10 rats) was given BER (100 mg/kg) by oral gavages daily for one month. A third group (10 rats) was given a combination of both BER and DOX in the above described dose and schedule. Results: Combination between DOX and BER was superior over their corresponding individual administrations as indicated by significant improvement in the overall estimated indices of liver function. Also, in comparison to individual therapy, this combination was obviously more potent to reduce the levels of novel HCC related tumor markers including serum AFP-L3 and tissue levels of Golgi protein 73, and glypican 3. Furthermore, histological investigations and assessments of hepatic tissue levels of some oxidative stress markers strongly confirmed the advantageous effects of combined BER and DOX in fighting DENA-induced HCC. Conclusion: our study conclusively revealed that combining BER with DOX exhibited a promising preclinical anticancer efficacy and could be considered as a novel strategy to synergistically combat HCC in clinical practices.

Abstract Background Patient position after spinal anesthesia has had variable effects on blood pressure and ephedrine requirements. The aim of this study was to determine the effects that sitting the patient up for five minutes after spinal anesthesia would have on intraoperative fluid and ephedrine requirements. Methods The study included 120 women at term gesta- tion who were scheduled for Cesarean delivery under spinal anesthesia. After anesthetic administration, the women were randomized either to sit up for five minutes then lie down (Group S) or to lie down immediately (Group L) to a tilted supine position. A blinded observer recorded sensory block level, systolic blood pressure, heart rate, ephedrine and fluid requirements, adverse events, and time to motor recovery (modified Bromage score of 2). Results Group S had a lower intraoperative sensory block height than Group L [T4 (1) vs T2 (1), respectively; P.001]; Group S also required less ephedrine (8% vs 47%, respectively; P.001), received less fluid [709 (59) mL vs 789 (90) mL, respectively; P.001], and experi- enced less nausea and vomiting (5% vs 22%, respectively; P = 0.014) and shortness of breath (3% vs 28%, respec- tively; P.001) intraoperatively. In Group S, the odds of requiring ephedrine were 0.09 compared with 0.89 in Group L (odds ratio 0.10). There were no differences in systolic blood pressure (P = 0.127) or heart rate (P = 0.831) over time between groups. Time to a modified Bromage score of 2 was longer in Group S than in Group L [101 (15) min vs 88 (14) min, respectively; P.001]. Conclusions Sitting the patient up for five minutes rather than laying the patient down immediately after spinal anesthesia for Cesarean delivery decreased intraoperative sensory block height, ephedrine and fluid requirements, and intraoperative nausea, vomiting, and shortness of breath without affecting systolic blood pressure or the success of the anesthetic. However, the method resulted in delayed postoperative motor recovery.

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Melasma is a common aesthetic problem characterized by facial hyperpigmentation. It frequently affects young to middle-aged females who are Hispanic or of Asian, African or Middle Eastern descent. Its pathogenesis is still mysterious with multiple factors are being accused to play a role. Although many treatment options are currently available, melasma is difficult to cure with tendency to relapse. Melasma (a term derived from the Greek word “melas” meaning black) is a worldwide prevalent acquired disorder of hyperpigmentation that commonly affects females with Fitzpatrick skin phototypes III-V (Goh and Dlova, 1999 and Gupta et al., 2006). It is characterized by appearance of symmetrical light to dark brown spots and patches on sun exposed areas mostly the face and especially the forehead, cheeks and chin (Kang and Ortonne, 2009). Melasma is sometimes termed chloasma (derived from the Greek word “chloas” meaning green) or mask of pregnancy when it develops in pregnant females (Handel et al., 2014a).

Melasma is a common aesthetic problem characterized by facial hyperpigmentation. It frequently affects young to middle-aged females who are Hispanic or of Asian, African or Middle Eastern descent. Its pathogenesis is still mysterious with multiple factors are being accused to play a role. Although many treatment options are currently available, melasma is difficult to cure with tendency to relapse. Melasma (a term derived from the Greek word “melas” meaning black) is a worldwide prevalent acquired disorder of hyperpigmentation that commonly affects females with Fitzpatrick skin phototypes III-V (Goh and Dlova, 1999 and Gupta et al., 2006). It is characterized by appearance of symmetrical light to dark brown spots and patches on sun exposed areas mostly the face and especially the forehead, cheeks and chin (Kang and Ortonne, 2009). Melasma is sometimes termed chloasma (derived from the Greek word “chloas” meaning green) or mask of pregnancy when it develops in pregnant females (Handel et al., 2014a).

Melasma is a common aesthetic problem characterized by facial hyperpigmentation. It frequently affects young to middle-aged females who are Hispanic or of Asian, African or Middle Eastern descent. Its pathogenesis is still mysterious with multiple factors are being accused to play a role. Although many treatment options are currently available, melasma is difficult to cure with tendency to relapse. Melasma (a term derived from the Greek word “melas” meaning black) is a worldwide prevalent acquired disorder of hyperpigmentation that commonly affects females with Fitzpatrick skin phototypes III-V (Goh and Dlova, 1999 and Gupta et al., 2006). It is characterized by appearance of symmetrical light to dark brown spots and patches on sun exposed areas mostly the face and especially the forehead, cheeks and chin (Kang and Ortonne, 2009). Melasma is sometimes termed chloasma (derived from the Greek word “chloas” meaning green) or mask of pregnancy when it develops in pregnant females (Handel et al., 2014a).

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Background: Gentamicin (GM) is an antibiotic that is widely used to treat many Gram-negative bacteria, such as those involved in urinary tract infections. However, being nephrotoxic, GM dose adjustment and reno-protective elements must be concurrently administered with GM to minimize kidney damage. Oxidative stress plays a pivotal role in the pathogenesis of GM-induced nephrotoxicity. Thymoquinone (TQ) is a promising therapeutic substance, that is being extensively studied in many diseases, such as diabetes mellitus, cancer, hypertension, and others. The powerful antioxidant properties of TQ may greatly help in minimizing GM nephrotoxicity. Metformin (MF) is a well-known, clinically approved oral hypoglycaemic drug that has many other actions, including antioxidant properties. The aim of this work was to evaluate the possible antioxidant and reno-protective effects of TQ and metformin in GM-induced nephrotoxicity in the same model (rats) at the same time. In addition, we aimed to further understand the effects underlying GM-induced nephrotoxicity. Methods: Twenty male rats were randomly divided into four equal groups: the first group (control) received distilled water; the second group received GM only; the third group received concurrent oral TQ and GM; and the fourth group received concurrent oral MF and GM. After 4 weeks, renal function and histopathology, as well as levels of the oxidative markers glutathione peroxidase-1 (GLPX1), superoxide dismutase (SOD), and malondialdehyde (MDA) in the kidney tissues, were assessed. Results: Compared with the control group, and as expected, the GM-injected rats showed significant biochemical and histological changes denoting renal damage. Compared with GM-injected rats, the concurrent administration of TQ with GM significantly reduced the levels of serum creatinine, serum urea, and tissue MDA and significantly increased the levels of GLPX1 and SOD. Concurrent metformin administration with GM significantly increased the levels of both GLPX1 and SOD and significantly decreased the levels of tissue MDA but had no significant effect on serum creatinine and urea levels. Compared with GM-injected rats, the addition of either TQ or MF resulted in a reduction in endothelial proliferation and mesangial hypercellularity. Conclusions: Both TQ and MF effectively alleviated the oxidative stress in GM-induced nephrotoxicity in rats, with TQ but not MF producing a complete reno-protective effect. Further studies for evaluation of different reno-protective mechanisms of TQ should be conducted.

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