Therapeutic effect of carnosine in rat model of experimental liver carcinogenesis.

The possible anticancer effect of carnosine versus doxorubicin was investigated against hepatocellular carcinoma (HCC) induced by trichloroacetic acid (TCA) (500mg/kg/day, p.o., for 5days) in rats. Following induction of HCC, rats treated with either carnosine (10mg/kg/day, i.p.), or doxorubicin (2.5mg/kg, i.p., once weekly), for 2 weeks. Carnosine significantly decreased serum alanine aminotransferase, and hepatic lipid peroxidation, nitric oxide, tumor necrosis factor-α, and nuclear factor-κB p65 unit, and significantly increased liver total antioxidant status in TCA-challenged rats. The effects of doxorubicin on oxidative, nitrative, and inflammatory biomarkers were less significant than carnosine. However, both carnosine and doxorubicin significantly induced liver tissue apoptotic biomarkers, Bax, cytosolic cytochrome C, and caspase-3, in a comparable manner. Additionally, carnosine and doxorubicin reduced the histopathological dysplastic changes, and alpha-fetoprotein expression in liver of rats with HCC. It was concluded that carnosine significantly protected against TCA-induced liver carcinogenesis in rats, through its antioxidant, antinitrative, and anti-inflammatory effects, and induction of apoptosis.

Epigallocatechin-3-gallate counters cisplatin toxicity of rat testes.

CONTEXT: Epigallocatechin-3-gallate (EG), the main active flavonoid in green tea, has well-known anti-inflammatory, antioxidant, and anti-apoptotic activities. OBJECTIVE: The EG protection against testicular injury induced by cisplatin was studied in Sprague-Dawley rats. MATERIALS AND METHODS: Cisplatin (10 mg/kg, i.p) was given as a single injection to rats. EG was given at 40 and 80 mg/kg/day, i.p., for 5 days, starting the same day of cisplatin insult. Serum testosterone, and testicular malondialdehyde, total antioxidant status, nitric oxide, interleukin-6, interleukin-1ß, cytochrome C, Bax/Bcl-2 ratio, and caspase-3 were measured. In addition, testicular histopathological examination and immunohistochemical expression of testicular tumour necrosis factor-α were evaluated. RESULTS: Cisplatin, compared to the control, significantly decreased serum testosterone (6.48 ± 0.7 vs. 50.8 ± 4.91 ng/10 mL), and testicular tissue antioxidant status (17.3 ± 1.21 vs. 64.12 ± 5.4 µmol/g), and significantly increased interleukin-6 (85.81 ± 6.11 vs. 38.2 ± 2.79 pg/100 mg), interleukin-1ß (98.09 ± 8.31 vs. 32.52 ± 2.08 pg/100 mg), malondialdehyde (74.5 ± 5.88 vs. 23.8 ± 1.91 nmol/g), nitric oxide (104.98 ± 8.5 vs. 52.68 ± 5.12 nmol/100 mg), cytochrome C (5.97 ± 0.33 vs. 1.6 ± 0.99 ng/mg protein), Bax/Bcl-2 ratio (4.01 ± 0.38 vs. 0.71 ± 0.0), and caspase-3 (3.2 ± 0.21 vs. 0.98 ± 0.08 O.D. 405 nm) in rat testes. EG (40 and 80 mg/kg, respectively) caused significant increases of serum testosterone (33.9 ± 2.89 and 47.88 ± 4.4 ng/10 mL), and testicular antioxidant status (47.1 ± 3.92 and 58.22 ± 3.58 µmol/g), and significant decreases of interleukin-6 (57.39 ± 4.2 and 48.18 ± 3.98 pg/100 mg), interleukin-1ß (65.12 ± 5.88 and 41.96 ± 3.51 pg/100 mg), malondialdehyde (42.3 ± 3.9 and 28.67 ± 2.49 nmol/g), nitric oxide (70.6 ± 6.79 and 61.31 ± 5.18 nmol/100 mg), cytochrome C (3.4 ± 0.27 and 2.21 ± 0.18 ng/mg protein), Bax/Bcl-2 ratio (1.49 ± 0.14 and 1.1 ± 0.09), and caspase-3 (2.1 ± 0.17 and 1.48 ± 0.13 O.D. 405 nm) in testes of cisplatin-treated rats. Additionally, both doses of EG significantly ameliorated the histopathological injury and reduced tumour necrosis factor-α expression in rat testes. CONCLUSION: EG can afford testicular protection in cisplatin-challenged rats by its antioxidant, antinitrative, anti-inflammatory and antiapoptotic effects.

Nephroprotection of punicalagin in rat model of endotoxemic acute kidney injury.

The potential nephroprotection of punicalagin (PNG) against lipopolysaccharide (LPS)-induced acute kidney injury in rats was investigated. Rats received a single i.v. dose of LPS (5 mg/kg), and treated with PNG (50 mg/kg, i.p.), 1 h before, and 1 h following LPS administration. LPS caused significant increases of serum creatinine and neutrophil gelatinase-associated lipocalin. LPS also resulted in significant increases in interleukin-18, tumor necrosis factor-α, interleukin-6, malondialdehyde, nitric oxide, Bax/Bcl-2 ratio and myeloperoxidase, inducible nitric oxide synthase, caspases 3, 8 and 9 activities, and a significant decrease in total antioxidant capacity in kidney tissues. PNG significantly ameliorated the alterations in the measured parameters. Additionally, PNG attenuated the histopathological injury and reduced kidney injury molecule-1 expression in kidneys of rats that received LPS. It was concluded that PNG ameliorated endotoxemic acute kidney injury in rats by counteracting inflammation, oxidative/nitrative stress and apoptosis.

Punicalagin alleviates hepatotoxicity in rats challenged with cyclophosphamide.

This study investigated the possible hepatoprotection of punicalagin in rats received cyclophosphamide (20mg/kg/day, i.p., for 7 days). Punicalagin given at two doses, 15 and 30mg/kg/day, p.o., for 7 days, starting the same day of cyclophosphamide administration. Punicalagin significantly and dose-dependently reduced the elevations of serum alanine aminotransferase, and liver nuclear factor-κB p65, tumor necrosis factor-α, interleukin-1ß, malondialdehyde, nitric oxide, Bax/Bcl-2 ratio, inducible nitric oxide synthase, caspases 3 and 9 activities, and prevented the decrease of hepatic total antioxidant capacity. Punicalagin also attenuated the histopathological liver tissue damage, and decreased cyclooxygenase-2 expression in liver of rats received cyclophosphamide in a dose-dependent manner. It was concluded that punicalagin protected rat liver against cyclophosphamide toxicity by inhibiting oxidative/nitrosative stress, inflammation, and apoptosis.

Assessment of ambient noise levels in the intensive care unit of a university hospital.

BACKGROUND: Noise is recognized as a source of hazard to the patient's environment. Studies have also shown that it has a direct impact on mortality and morbidity as a result of sleep deprivation which affects the immunity of critically ill patients. OBJECTIVES: The aim of this study was to measure levels of environmental noise in a six- bed, open-plan general medical intensive care unit (MICU). METHODS: Levels of exposure to environmental noise were assessed in the intensive care unit of King Fahad Hospital of the University (KFHU) where measurements of environmental noise were taken using calibrated sound level meter during shifts of working days and weekends. RESULTS: Statistical analysis revealed that there were no significant differences between noise levels in the morning, evening and night shifts of working days and weekends in the ICU of KFHU (p value =0.155, 0.53 and 0.711) respectively. There was no significant difference between overall level of exposure to noise in the working days and weekends as well (p-value=0.71). However, the assessed levels of exposures to noise were still higher than stipulated international standards. CONCLUSION: Some sources of environmental noise, such as the use of oxygen, suction equipment or respirators are unavoidable. Nevertheless, hospital ICUs should have measures to minimize the level of exposure to noise in the ICU. Further research in this area might focus on the noise level and other modifiable environmental stress factors in the ICU that affect patients as well as the staff.

Obstetric admissions to the intensive care unit: a 12-year review.

OBJECTIVE: The objective was to ascertain the prevalence, causes and outcome of critically ill obstetric patients admitted to the intensive care unit (ICU). DESIGN: The design was a retrospective collection of data. SETTINGS: The setting was a multidisciplinary ICU in a University hospital. PATIENTS: All obstetric patients admitted to the ICU over a 12-year period from May 1992 to April 2004 were reviewed. METHODS: Data collected included demographic characteristics of the patients, pre-existing medical conditions, obstetric complications, invasive procedures required in the ICU and outcome of the patients. RESULTS: The incidence of obstetric admissions to the ICU represented 0.22% of all deliveries during the study period. The majority (84.4%) of patients were admitted to the ICU postpartum. Obstetric haemorrhage (32.8%) and pregnancy-induced hypertension (17.2%) were the two main obstetrical reasons for admission. The remainder included medical disorders (37.5%) and other causes (6.2%). Associated major complications included adult respiratory distress syndrome (ARDS) and HELLP (haemolysis, elevated liver enzymes and low platelets) syndrome. The perinatal mortality rate was 20% and the maternal mortality rate 9.4%. CONCLUSIONS: A team approach consisting treatment by obstetricians, intensive care specialists and anaesthesiologists provided optimal care for the patients. Improved management strategies for obstetric haemorrhage and hypertension may significantly reduce maternal morbidity.

Acute respiratory failure revealing Guillain-Barre syndrome.

This article reports the occurrence of Guillain-Barre syndrome in a critically ill patient manifesting as a "difficult-to-wean" patient. This uncommon but possible etiology is worth noting by physicians in the intensive care unit.