Thearubigins protect against acetaminophen-induced hepatic and renal injury in mice: biochemical, histopathological, immunohistochemical, and flow cytometry study.

CONTEXT: Acetaminophen toxicity is used as a model for studying chemical toxicity. N-acetylcysteine (NAC) is used for the treatment of hepatotoxicity; however, there is no specific therapy for nephrotoxicity. OBJECTIVE: This study was designed to investigate the potential protective effect of black tea extract (BTE) and its main phenolic pigment, thearubigins (TRs), against acetaminophen (APAP)-induced hepatic and renal injury in mice. MATERIALS AND METHODS: Besides control groups, six groups (n = 8) were given intraperitoneally APAP (300 mg/kg) and then after 1.5 hours were treated intraperitoneally as follows: NAC (318 mg/kg), BTE (3%, 4.5%), and TRs (50, 60, and 70 mg/kg). Six hours post-APAP injection, blood was collected for biochemical measurements. Later, liver and kidneys were removed for histopathological, immunohistochemical, and flow cytometry studies. RESULTS: APAP increased alanine aminotransferase and malondialdehyde and decreased glutathione levels in blood. Treatments significantly reversed these changes mostly with NAC and TRs70. TRs showed dose-dependent significant differences. The APAP-induced central lobular hepatic necrosis and increased TUNEL positivity were mild with co-administration of NAC and TRs (60, 70) while moderate with co-administration of BTE (3, 4.5) and TRs50. The APAP-increased serum creatinine level was significantly reversed by treatments (mostly TRs60, 70). The APAP-induced renal tubular epithelial degeneration and necrosis were mild with co-administration of TRs (60, 70) while moderate with co-administration of NAC, BTE (3, 4.5), and TRs50. The APAP-accumulated apoptotic cells in sub-G1 phase were significantly decreased by treatments, mostly by NAC and TRs70 in the liver and TRs (60, 70) in kidneys. CONCLUSION: Thearubigins protected against acetaminophen-induced hepatotoxicity and nephrotoxicity in mice possibly through their antioxidant activity.

A randomized, double-blind, placebo-controlled, dose ranging study to assess the efficacy and safety of eltrombopag in patients receiving carboplatin/paclitaxel for advanced solid tumors.

OBJECTIVES: Eltrombopag, an oral, nonpeptide thrombopoietin receptor agonist, has been shown to increase platelet counts in adults with chronic immune thrombocytopenia and chronic hepatitis C. This multicenter phase 2 study assessed the efficacy and safety of eltrombopag in patients receiving first-line carboplatin/paclitaxel for the treatment of advanced solid tumors. RESEARCH DESIGN AND METHODS: Patients (N = 183) were randomized to placebo or eltrombopag 50 mg, 75 mg, or 100 mg given orally following chemotherapy on days 2 through 11 of each 21-day cycle, for at least two cycles. The primary endpoint was the difference in platelet count from day 1 in cycle 2 to the platelet nadir in cycle 2. CLINICAL TRIAL REGISTRY NUMBER: NCT00102726. RESULTS: Although the primary endpoint was not met, postnadir platelet counts increased during cycles 1 and 2 in all eltrombopag treatment groups compared with placebo. The most commonly reported adverse events across all study arms (including placebo) were nausea and alopecia and eltrombopag was generally well tolerated. CONCLUSIONS: This study provides preliminary information that eltrombopag does increase platelets in patients receiving chemotherapy for advanced solid tumors. Further investigation is needed to identify the optimal dose(s) and schedule of eltrombopag in patients receiving myelosuppressive chemotherapy.

Physical chemical approach versus traditional technique in analyzing blood gases and electrolytes during liver transplant surgery.

INTRODUCTION: Sodium, chloride, and lactic acid load may be responsible for acidosis during surgery; complex disorders may not have a single, identifiable causative anion, with only the strong ion gap (SIG) being elevated. We studied the effects of fluids infused during various phases of liver transplant surgeries on acid-base and electrolyte changes using the Henderson-Hasselbach and Stewart equations. METHODS: This retrospective, descriptive, cohort study included 40 liver transplant recipients. All patients received intraoperative fluids in the form of normal saline (0.9%) Ringer's lactate, and albumin (5%) to achieve a stable hemodynamic state. Arterial blood gas and electrolyte analyses were performed as well as measurements of serum albumin and lactate levels. Using the Stewart approach we calculated the strong ion difference, and the corrected anion gap. RESULTS: High levels of SIG were observed in the absence of acid-base abnormalities using traditional acid-base measurements after induction versus during the dissection phases: anion gap of 7.1+/-2.3 versus 12.4+/-1.8 mmol/L, pH, 7.34+/-.05 versus 7.28+/-0.06 and PCO2 of 4.8+/-0.2 versus 5.3 KPa, respectively. Patients had a SIDe of 27.9+/-5.6 versus 33.5+/-2.4 mmol/L and a SIG of 4.8+/-2.2 versus 9.3+/-2.3 mmol/L, respectively. During the anhepatic versus the reperfusion phases, the SIG increased to 12.9+/-2.1 and 9.5+/-1.8 versus 14+/-2.5 and 12.6+/-2.0 mmol/L changes in anion gap. There was a strong correlation between SIG and pH. CONCLUSION: Avoiding large quantities of sodium chloride-containing fluids may help to decrease the incidence of hyperchloremic acidosis among this group of patients. The changes in SIG but not in bicarbonate during liver transplant procedures were highly correlated with pH changes.

Clinical outcomes for Saudi and Egyptian patients receiving deceased donor liver transplantation in China.

Long waiting list times in liver transplant programs in Saudi Arabia and unavailability of deceased donor transplantation in Egypt have led several patients to seek transplantation in China. All patients who received transplants in China and followed in three centers from January 2003-January 2007 were included. All patients' charts were reviewed. Mortality and morbidity were compared to those transplanted in King Faisal Specialist Hospital & Research Centre (KFSH&RC) during the same period. Seventy-four adult patients were included (46 Saudi nationals; 28 Egyptians). One-year and 3-year cumulative patient survival rates were 83% and 62%, respectively compared to 92% and 84% in KFSH&RC. One-year and 3-year cumulative graft survival rates were 81% and 59%, respectively compared to 90% and 84% in KFSH&RC. Compared to KFSH&RC, the incidence of complications was significantly higher especially biliary complications, sepsis, metastasis and acquired HBV infection posttransplant. Requirements of postoperative interventions and hospital admissions were also significantly greater. Our data show high mortality and morbidity rates in Saudi and Egyptian patients receiving transplants in China. This could be related to more liberal selection criteria, use of donation after cardiac death (DCD) donors or possibly more limited posttransplant care.

Cooling intravenous fluids by refrigeration: implications for therapeutic hypothermia.

BACKGROUND: ILCOR recommend the use of therapeutic hypothermia (32-34 degrees C) for 12-24 h in unconscious adult patients with spontaneous circulation after cardiac arrest with a VF rhythm. Among various methods of inducing hypothermia, the rapid infusion of ice-cold intravenous fluid has been used. METHODS: To investigate the time required to cool intravenous fluids in a domestic refrigerator and freezer, bags of compound sodium lactate were placed on the upper shelf of a refrigerator. Continuous temperature measurement was performed for 2 h for 10 500 ml and 10 1000 ml bags. The procedure was then repeated in the freezer. RESULTS: The mean time for 500 ml bags to cool to 4 degrees C or below was 90 minutes or more in a refrigerator and 60-90 minutes in the freezer. 1000 ml bags are cooled to 4 degrees C or below within 120 minutes in the freezer, but it takes longer in a refrigerator. CONCLUSION: As induced hypothermia should be started as soon as possible in eligible patients, crystalloids should be stored in a refrigerator.

Role of diffusion-weighted echo-planar MR imaging in differentiation of residual or recurrent head and neck tumors and posttreatment changes.

BACKGROUND AND PURPOSE: The purpose of this work was to evaluate whether diffusion-weighted MR imaging can be used in differentiating residual or recurrent head and neck tumors from postoperative or postradiation changes. MATERIALS AND METHODS: This study included 32 patients clinically suspected for recurrent head and neck tumor after surgery (n=3), radiation therapy (n=13), or both (n=16). Diffusion-weighted MR imaging was done by using a single-shot spin-echo echo-planar sequence. The apparent diffusion coefficient (ADC) value of the suspected lesion was calculated and correlated with pathologic results. RESULTS: Adequate diffusion-weighted MR images and ADC maps were obtained in 30 patients (93.8%). The mean ADC value of residual or recurrent lesions (1.17 +/- 0.33 x 10(-3) mm(2)/s) was less than that of posttherapeutic changes (2.07 +/- 0.25 x 10(-3) mm(2)/s), and the difference was statistically significant (P<.001). When an ADC value of 1.30 x 10(-3) mm(2)/s was used as a threshold value for differentiation, the best results were obtained with an accuracy of 87%, sensitivity of 84%, specificity of 90%, positive predictive value of 94%, and negative predictive value of 76%. CONCLUSIONS: Diffusion-weighted MR imaging with ADC measurement has promising results for differentiating residual or recurrent head and neck tumors from postoperative or postradiation changes.

Effects of dorsal column spinal cord stimulation (DCS) on reversibility of neuronal function--experience of treatment for vegetative states.

We have reported that DCS (dorsal column stimulation) improves the clinical symptoms of cases in persistent vegetative states. Since then, we have accumulated 23 cases who have been treated by DCS. We describe the clinical EEG, rCBF, and biochemical changes in cerebrospinal fluid (CSF) caused by DCS in patients in persistent vegetative states: (1) eight of these cases showed good clinical improvement; (2) most patients were young and the CT scan did not show large, diffuse, definite or bilateral low density areas in cortex, brainstem of thalmus; (3) neurostimulation increased rCBF (cerebral blood flow) in many parts of the brain in cases with vegetative states; blood flow increased in the cerebrum, cerebellum and brainstem; (4) neurostimulation enhanced the metabolism of catecholamines in CSF, NE, DA, DOPAC, HVA, and 5HIAA increased, but 3MT and 5HT decreased in CSF. DCS increased rCBF, enhanced the metabolism of catecholamines in CSF, and improved the EEG in patients in persistent vegetative states.

Aflatoxin and aflatoxicosis. I. Fungal flora of some food and animal feeds with special references to aflatoxin-producing abilities.

A wide range of fungi, amounting to fifty-six species belonging to twenty-two genera, have been recovered from animal feeds and foodstuffs. The most frequent fungi were Aspergillus niger, and A. flavus, followed by Mucor racemosus, Alternaria alternata. Rhizopus stolonifer, Penicillium corylophilum and P. notatum. Three genera were found to be of moderate occurrence, namely, Mucor, Rhizopus and alternaria. The three following genera were of low occurrence: cladosporium, Fusarium, and Neurospora. The fluorescence method of detecting aflatoxin-producing strains demonstrated that only one is isolated of A. flavus possesses this property. Certain species of Penicillium and Aspergillus produced fluorescent substances (metabolites) similar in color to B and G aflatoxin. These substances were subsequently proved not to be aflatoxin by (TLC) chromatography. The animal and public health significance from such toxins was also discussed.

Aflatoxin and aflatoxicosis. II. Effects of aflatoxin on ovaries and testicles in mature domestic fowls.

The present study aimed at: 1. Examination of commercial chicken and duck eggs for the possible presence of aflatoxins. 2. Study of the sex susceptibility of mature chickens when fed on ration containing aflatoxins. 3. Study of clinicopathological effects on their ovaries and testicles. In this investigation, 100 chicken and 50 duck eggs collected from markets in the vicinity of Assiut Governorate, were examined individually for the presence of aflatoxins in the whites and yolks. The study revealed that the examined eggs contained no aflatoxins. Experimentally, aflatoxin BV(8.1 ppm) and G. (1.6 ppm) were incorporated into the feed of five laying hens and five mature cooks for three weeks duration. The layers showed cessation of egg production during the whole feeding period. Histopathological examinations revealed that, the ovaries showed follicular atresia while testicles were normal. It was shown that, aflatoxicosis cause pathological changes in the chicken ovaries, which has a detrimental effect on egg production.

Determining the kinetic behaviour for the secretion of milk toxin as related to dosage level of aflatoxin B1.

39 species which belong to 14 genera were isolated from 110 milk samples collected from different dairy sources at Assiut City. The most frequent fungi were A. niger, A flavus and Clasdosporium cladosporioides, followed by Curvularia spicifera and Penicillium corylophilum. The remaining species were of rare occurrence. The fluorescence-method for detecting aflatoxin-producing strains demonstrated the presence of two isolates namely A. flavus possesses this property. One of these toxic isolates was proved to produce high level of aflatoxin B1. It was used as a tool for determining the kinetic behaviour for the secretion of M1 toxin in milk of lactating animals which had received a toxic diet. The results revealed the following: 1. The milk toxin was detected in the milk of lactating animals next day after the toxin-containing ration was fed. 2. The level of milk toxin is gradually decreased when the feeding programme was interrupted. 3. When the animals supplied a ration containing the same concentration of aflatoxin for successive days, the milk toxin concentration was maintained at the same level. 4. The total amount of milk toxin secreted was less than one per cent of the amount of aflatoxin B1 received. 5. The concentration of milk toxin secreted by goats was higher than that of dairy cows. 6. Milk toxin failed to be detected five days after the feeding programme was discontinued.